Compositions of selenoorganic compounds and methods of use thereof
The present application relates to compositions comprising selenium compounds, such as 5′-Methylselenoadenosine, Se-Adenosyl-L-homocysteine, Gamma-glutamyl-methylseleno-cysteine, a compound of Formula (I), Formula (II), or Formula (III), and combinations thereof, and methods of using the same for modulating glucose metabolism in a subject.
1. A method of replacing insulin in a subject comprising:
administering a composition to the subject, the composition comprising at least three different compounds selected from the group consisting of 5′-Methylselenoadenosine, Se-Adenosyl-L-homocysteine, Gamma-glutamyl-methylseleno-cysteine, a compound of Formula (I), a compound of Formula (II), and a compound of Formula (III); and a carrier, wherein the composition contains at least about 0.033% (w/v) of each of the at least three different compounds that is selected, wherein Formula (I) is:
or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein
R 1 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′, or C(O)OR′, wherein R′ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 2 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′″, or C(O)OR′″, wherein R′″ is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 3 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 4 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 5 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 6 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 7 is a C 3 -C 16 alkyl, alkenyl, alkynyl, ketone, amino alcohol, amino acid, OR a , Se—R b , or S—R b , wherein R a for OR a is selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, where R b for Se—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, wherein R b for S—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, and wherein the amino acid is selected from the group consisting of arginine, histidine, lysine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, selenocysteine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; and
R 8 is hydrogen, azido, alkyl, alkenyl, or alkynyl,
wherein Formula (II) is:
or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein
R 1 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′, or C(O)OR′, wherein R′ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 2 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C C(O)R′″, or C(O)OR′″, wherein R′″ is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 3 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 4 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 5 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 6 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 8 is hydrogen, azido, alkyl, alkenyl, or alkynyl;
R 9 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R c , or C(O)OR c , where R c is alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 9 together with R 10 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 10 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R c , or C(O)OR c , where R c is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 9 together with R 10 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen; and
R 11 is OR, alkoxy, aralkoxy, or amino, where R is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl, and
wherein Formula (III) is:
or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein
R 1 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′, or C(O)OR′, wherein R′ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 2 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C C(O)R′″, or C(O)OR′″, wherein R′″ is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 3 is OH, OR, alkoxy, aralkoxy, or amino, where R is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl;
R 4 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl;
R 5 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 6 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl; and
R 7 is a C 3 -C 16 alkyl, alkenyl, alkynyl, ketone, amino alcohol, amino acid, OR a , Se—R b , or S—R b , wherein R a for OR a is selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, where R b for Se—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, wherein R b for S—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, and wherein the amino acid is selected from the group consisting of arginine, histidine, lysine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, selenocysteine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan.
2. A method of enhancing insulin activity in a subject comprising:
administering a composition to the subject, the composition comprising at least three different compounds selected from the group consisting of 5′-Methylselenoadenosine, Se-Adenosyl-L-homocysteine, Gamma-glutamyl-methylseleno-cysteine, a compound of Formula (I), a compound of Formula (II), and a compound of Formula (III); and a carrier, wherein the composition contains at least about 0.033% (w/v) of each of the at least three different compounds that is selected, wherein Formula (I) is:
or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein
R 1 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′, or C(O)OR′, wherein R′ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 2 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′″, or C(O)OR′″, wherein R′″ is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 3 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 4 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 5 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 6 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 7 is a C 3 -C 16 alkyl, alkenyl, alkynyl, ketone, amino alcohol, amino acid, OR a , Se—R b , or S—R b , wherein R a for OR a is selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, where R b for Se—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, wherein R b for S—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, and wherein the amino acid is selected from the group consisting of arginine, histidine, lysine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, selenocysteine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; and
R 8 is hydrogen, azido, alkyl, alkenyl, or alkynyl,
wherein Formula (II) is:
or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein
R 1 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′, or C(O)OR′, wherein R′ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 2 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′″, or C(O)OR′″, wherein R′″ is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 3 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 4 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 5 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 6 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 8 is hydrogen, azido, alkyl, alkenyl, or alkynyl;
R 9 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R c , or C(O)OR c , where R c is alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 9 together with R 10 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 10 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R c , or C(O)OR c , where R c is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 9 together with R 10 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen; and
R 11 is OR, alkoxy, aralkoxy, or amino, where R is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl, and
wherein Formula (III) is:
or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein
R 1 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′, or C(O)OR′, wherein R′ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 2 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′″, or C(O)OR′″, wherein R′″ is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 3 is OH, OR, alkoxy, aralkoxy, or amino, where R is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl;
R 4 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl;
R 5 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 6 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl; and
R 7 is a C 3 -C 16 alkyl, alkenyl, alkynyl, ketone, amino alcohol, amino acid, OR a , Se—R b , or S—R b , wherein R a for OR a is selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, where R b for Se—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, wherein R b for S—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, and wherein the amino acid is selected from the group consisting of arginine, histidine, lysine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, selenocysteine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan.
3. The method of claim 2 , further comprising administering insulin or an analog or derivative thereof.
4. A method of inhibiting glucose production in a subject comprising:
administering a composition to the subject, the composition comprising at least three different compounds selected from the group consisting of 5′-Methylselenoadenosine, Se-Adenosyl-L-homocysteine, Gamma-glutamyl-methylseleno-cysteine, a compound of Formula (I), a compound of Formula (II), and a compound of Formula (III); and a carrier, wherein the composition contains at least about 0.033% (w/v) of each of the at least three different compounds that is selected, wherein Formula (I) is:
or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein
R 1 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′, or C(O)OR′, wherein R′ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 2 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′″, or C(O)OR′″, wherein R′″ is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 3 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 4 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 5 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 6 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 7 is a C 3 -C 16 alkyl, alkenyl, alkynyl, ketone, amino alcohol, amino acid, OR a , Se—R b , or S—R b , wherein R a for OR a is selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, where R b for Se—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, wherein R b for S—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, and wherein the amino acid is selected from the group consisting of arginine, histidine, lysine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, selenocysteine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; and
R 8 is hydrogen, azido, alkyl, alkenyl, or alkynyl,
wherein Formula (II) is:
or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein
R 1 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′, or C(O)OR′, wherein R′ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 2 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′″, or C(O)OR′″, wherein R′″ is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 3 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 4 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 5 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 6 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 8 is hydrogen, azido, alkyl, alkenyl, or alkynyl;
R 9 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R c , or C(O)OR c , where R c is alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 9 together with R 10 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 10 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R c , or C(O)OR c , where R c is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 9 together with R 10 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen; and
R 11 is OR, alkoxy, aralkoxy, or amino, where R is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl, and
wherein Formula (III) is:
or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein
R 1 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′, or C(O)OR′, wherein R′ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 2 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′″, or C(O)OR′″, wherein R′″ is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 3 is OH, OR, alkoxy, aralkoxy, or amino, where R is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl;
R 4 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl;
R 5 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 6 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl; and
R 7 is a C 3 -C 16 alkyl, alkenyl, alkynyl, ketone, amino alcohol, amino acid, OR a , Se—R b , or S—R b , wherein R a for OR a is selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, where R b for Se—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, wherein R b for S—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, and wherein the amino acid is selected from the group consisting of arginine, histidine, lysine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, selenocysteine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan.
5. A method of modulating glucose metabolism in a subject comprising:
administering a composition to the subject, the composition comprising at least three different compounds selected from the group consisting of 5′-Methylselenoadenosine, Se-Adenosyl-L-homocysteine, Gamma-glutamyl-methylseleno-cysteine, a compound of Formula (I), a compound of Formula (II), and a compound of Formula (III); and a carrier, wherein the composition contains at least about 0.033% (w/v) of each of the at least three different compounds that is selected, wherein Formula (I) is:
or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein
R 1 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′, or C(O)OR′, wherein R′ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 2 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′″, or C(O)OR′″, wherein R′″ is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 3 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 4 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 5 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 6 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 7 is a C 3 -C 16 alkyl, alkenyl, alkynyl, ketone, amino alcohol, amino acid, OR a , Se—R b , or S—R b , wherein R a for OR a is selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, where R b for Se—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, wherein R b for S—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, and wherein the amino acid is selected from the group consisting of arginine, histidine, lysine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, selenocysteine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; and
R 8 is hydrogen, azido, alkyl, alkenyl, or alkynyl,
wherein Formula (II) is:
or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein
R 1 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′, or C(O)OR′, wherein R′ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 2 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′″, or C(O)OR′″, wherein R′″ is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 3 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 4 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 5 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 6 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 8 is hydrogen, azido, alkyl, alkenyl, or alkynyl;
R 9 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R c , or C(O)OR c , where R c is alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 9 together with R 10 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 10 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R c , or C(O)OR c , where R c is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 9 together with R 10 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen; and
R 11 is OR, alkoxy, aralkoxy, or amino, where R is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl, and
wherein Formula (III) is:
or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein
R 1 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′, or C(O)OR′, wherein R′ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 2 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′″, or C(O)OR′″, wherein R′″ is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 3 is OH, OR, alkoxy, aralkoxy, or amino, where R is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl;
R 4 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl;
R 5 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 6 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl; and
R 7 is a C 3 -C 16 alkyl, alkenyl, alkynyl, ketone, amino alcohol, amino acid, OR a , Se—R b , or S—R b , wherein R a for OR a is selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, where R b for Se—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, wherein R b for S—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, and wherein the amino acid is selected from the group consisting of arginine, histidine, lysine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, selenocysteine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan.
6. The method of claim 1 , wherein the composition comprises 5′-Methylselenoadenosine, Se-Adenosyl-L-homocysteine and Gamma-glutamyl-methylseleno-cysteine.
7. The method of claim 2 , wherein the composition comprises 5′-Methylselenoadenosine, Se-Adenosyl-L-homocysteine and Gamma-glutamyl-methylseleno-cysteine.
8. The method of claim 3 , wherein the composition comprises 5′-Methylselenoadenosine, Se-Adenosyl-L-homocysteine and Gamma-glutamyl-methylseleno-cysteine.
9. The method of claim 4 , wherein the composition comprises 5′-Methylselenoadenosine, Se-Adenosyl-L-homocysteine and Gamma-glutamyl-methylseleno-cysteine.
10. The method of claim 5 , wherein the composition comprises 5′-Methylselenoadenosine, Se-Adenosyl-L-homocysteine and Gamma-glutamyl-methylseleno-cysteine.
11. The method of claim 1 , wherein the composition comprises at least 0.1% (w/v) of 5′-Methylselenoadenosine.
12. The method of claim 2 , wherein the composition comprises at least 0.1% (w/v) of 5′-Methylselenoadenosine.
13. The method of claim 3 , wherein the composition comprises at least 0.1% (w/v) of 5′-Methylselenoadenosine.
14. The method of claim 4 , wherein the composition comprises at least 0.1% (w/v) of 5′-Methylselenoadenosine.
15. The method of claim 5 , wherein the composition comprises at least 0.1% (w/v) of 5′-Methylselenoadenosine.
16. The method of claim 1 , wherein the composition further comprises insulin or an analog or derivative thereof.
17. The method of claim 2 , wherein the composition further comprises insulin or an analog or derivative thereof.
18. The method of claim 3 , wherein the composition further comprises insulin or an analog or derivative thereof.
19. The method of claim 4 , wherein the composition further comprises insulin or an analog or derivative thereof.
20. The method of claim 5 , wherein the composition further comprises insulin or an analog or derivative thereof.
21. The method of claim 1 , wherein the composition further comprises an insulin sensitizer, an insulin secretagogue, or an incretin mimetic.
22. The method of claim 2 , wherein the composition further comprises an insulin sensitizer, an insulin secretagogue, or an incretin mimetic.
23. The method of claim 3 , wherein the composition further comprises an insulin sensitizer, an insulin secretagogue, or an incretin mimetic.
24. The method of claim 4 , wherein the composition further comprises an insulin sensitizer, an insulin secretagogue, or an incretin mimetic.
25. The method of claim 1 , wherein the composition excludes one or more of 5′-Methylthioadenosine, S-Adenosyl-L-homocysteine or Gamma-glutamyl-methyl-cysteine.
26. The method of claim 2 , wherein the composition excludes one or more of 5′-Methylthioadenosine, S-Adenosyl-L-homocysteine or Gamma-glutamyl-methyl-cysteine.
27. The method of claim 3 , wherein the composition excludes one or more of 5′-Methylthioadenosine, S-Adenosyl-L-homocysteine or Gamma-glutamyl-methyl-cysteine.
28. The method of claim 4 , wherein the composition excludes one or more of 5′-Methylthioadenosine, S-Adenosyl-L-homocysteine or Gamma-glutamyl-methyl-cysteine.
29. The method of claim 5 , wherein the composition excludes one or more of 5′-Methylthioadenosine, S-Adenosyl-L-homocysteine or Gamma-glutamyl-methyl-cysteine.
30. A composition comprising at least two different compounds selected from the group consisting of 5′-Methylselenoadenosine, Se-Adenosyl-L-homocysteine, Gamma-glutamyl-methylseleno-cysteine, a compound of Formula (I), a compound of Formula (II), and a compound of Formula (III); and a carrier, wherein the composition contains at least about 0.033% (w/v) of each of the at least two different compounds that is selected, wherein Formula (I) is:
or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein
R 1 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′, or C(O)OR′, wherein R′ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 2 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′″, or C(O)OR′″, wherein R′″ is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 3 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 4 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 5 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 6 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 7 is a C 3 -C 16 alkyl, alkenyl, alkynyl, ketone, amino alcohol, amino acid, OR a , Se—R b , or S—R b , wherein R a for OR a is selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, where R b for Se—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, wherein R b for S—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, and wherein the amino acid is selected from the group consisting of arginine, histidine, lysine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, selenocysteine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; and
R 8 is hydrogen, azido, alkyl, alkenyl, or alkynyl,
wherein Formula (II) is:
or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein
R 1 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′, or C(O)OR′, wherein R′ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 2 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′″, or C(O)OR′″, wherein R′″ is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 3 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 4 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 5 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 6 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 8 is hydrogen, azido, alkyl, alkenyl, or alkynyl;
R 9 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R c , or C(O)OR c , where R c is alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 9 together with R 10 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 10 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R c , or C(O)OR c , where R c is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 9 together with R 10 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen; and
R 11 is OR, alkoxy, aralkoxy, or amino, where R is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl, and
wherein Formula (III) is:
or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein
R 1 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′, or C(O)OR′, wherein R′ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 2 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′″, or C(O)OR′″, wherein R′″ is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 3 is OH, OR, alkoxy, aralkoxy, or amino, where R is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl;
R 4 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl;
R 5 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 6 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl; and
R 7 is a C 3 -C 16 alkyl, alkenyl, alkynyl, ketone, amino alcohol, amino acid, OR a , Se—R b , or S—R b , wherein R a for OR a is selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, where R b for Se—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, wherein R b for S—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, and wherein the amino acid is selected from the group consisting of arginine, histidine, lysine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, selenocysteine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan.
31. A composition comprising at least three different compounds selected from the group consisting of 5′-Methylselenoadenosine, Se-Adenosyl-L-homocysteine, Gamma-glutamyl-methylseleno-cysteine, a compound of Formula (I), a compound of Formula (II), and a compound of Formula (III); and a carrier, wherein the composition contains at least about 0.033% (w/v) of each of the at least three different compounds that is selected, wherein Formula (I) is:
or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein
R 1 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′, or C(O)OR′, wherein R′ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 2 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′″, or C(O)OR′″, wherein R′″ is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 3 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 4 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 5 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 6 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 7 is a C 3 -C 16 alkyl, alkenyl, alkynyl, ketone, amino alcohol, amino acid, OR a , Se—R b , or S—R b , wherein R a for OR a is selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, where R b for Se—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, wherein R b for S—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, and wherein the amino acid is selected from the group consisting of arginine, histidine, lysine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, selenocysteine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan; and
R 8 is hydrogen, azido, alkyl, alkenyl, or alkynyl,
wherein Formula (II) is:
or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein
R 1 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′, or C(O)OR′, wherein R′ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 2 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′″, or C(O)OR′″, wherein R′″ is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 3 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 4 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, carboxyl, or C-amido; or R 3 together with R 4 and the atoms to which they are attached form a heterocyclic ring having 4 to 8 ring members with at least two heteroatoms selected from oxygen;
R 5 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 6 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 8 is hydrogen, azido, alkyl, alkenyl, or alkynyl;
R 9 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R c , or C(O)OR c , where R c is alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 9 together with R 10 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 10 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R c , or C(O)OR c , where R c is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 9 together with R 10 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen; and
R 11 is OR, alkoxy, aralkoxy, or amino, where R is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl, and
wherein Formula (III) is:
or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein
R 1 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′, or C(O)OR′, wherein R′ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 2 is H, acyl, alkyl, alkenyl, alkynyl, aralkyl, carboxyl, cycloalkyl, C(O)R′″, or C(O)OR′″, wherein R′″ is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl; or R 1 together with R 2 form a heterocyclic ring having 4 to 8 ring members with at least one heteroatom selected from nitrogen;
R 3 is OH, OR, alkoxy, aralkoxy, or amino, where R is selected from alkyl, cycloalkyl, aryl, aralkyl, or heterocyclyl;
R 4 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, or heterocyclyl;
R 5 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl;
R 6 is oxo, hydroxyl, alkyl, alkenyl, alkynyl, OR″, or is absent; wherein R″ is selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or aralkyl; and
R 7 is a C 3 -C 16 alkyl, alkenyl, alkynyl, ketone, amino alcohol, amino acid, OR a , Se—R b , or S—R b , wherein R a for OR a is selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, where R b for Se—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, wherein R b for S—R b is selected from the group consisting of H, C 3 -C 16 alkyl, cycloalkyl, aryl, aralkyl, and heterocyclyl, and wherein the amino acid is selected from the group consisting of arginine, histidine, lysine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, selenocysteine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, and tryptophan.
32. The composition of claim 30 , wherein a compound according to the Formula (I) is included in the at least two different compounds that are selected.
33. The composition of claim 30 , wherein a compound according to the Formula (II) is included in the at least two different compounds that are selected.
34. The composition of claim 30 , wherein a compound according to the Formula (III) is included in the at least two different compounds that are selected.