ANTILEISHMANIAL COMPOSITIONS AND METHODS OF USE
In one aspect, the invention relates methods and compositions for treating parasitic diseases, for example, leishmaniasis. In a further aspect, the compounds of the methods and compositions are isolated from Pentalinon andrieuxii . This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
1 . A method for the treatment of a parasitic disease in a mammal diagnosed with the disease, the method comprising the step of administering to the mammal a therapeutically effective amount of at least one compound having a structure represented by a formula:
wherein each ---- is independently an optional covalent bond, wherein valence is satisfied;
wherein R 1 , when present, is selected from C1-C12 alkyl and C1-C12 alkenyl;
wherein R 2 , when present, is selected from C1-C12 alkyl and C1-C12 alkenyl;
wherein R 7 is selected from hydrogen, hydroxyl, amino, and halogen; and
wherein R 8 is selected from hydrogen and C1-C6 alkyl;
or a pharmaceutically acceptable salt, solvate, or polymorph thereof.
2 . The method of claim 1 , wherein the parasitic disease is associated with infection of the mammal by Leishmania spp.
3 . The method of claim 2 , wherein Leishmania spp. is selected from Leishmania donovani, Leishmannia brasiliensis, Leishmania mexicana, Leishmania amazonensis, Leishmania aethiopica, Leishmania major, Leishmania chagasi, Leishmania panamensis, Leishmania infantum , and Leishmania tropica.
4 . The method of claim 1 , wherein the parasitic disease is a leishmaniases.
5 . The method of claim 4 , wherein the leishmaniases is cutaneous leishmaniasis.
6 . The method of claim 4 , wherein the leishmaniases is visceral leishmaniasis.
7 . The method of claim 1 , wherein the mammal is human.
8 . The method of claim 1 , wherein R 1 is selected from:
9 . The method of claim 1 , wherein R 2 is selected from:
10 . The method of claim 1 , wherein the compound has a structure represented by a formula:
wherein each of R 4a and R 4b is independently selected from hydrogen and C1-C12 alkyl;
or a pharmaceutically acceptable salt, solvate, or polymorph thereof.
11 . The method of claim 1 , wherein the compound has a structure represented by a formula:
wherein each of R 6a and R 6b is independently selected from hydrogen and C1-C12 alkyl;
or a pharmaceutically acceptable salt, solvate, or polymorph thereof.
12 . The method of claim 1 , wherein the compound is selected from:
13 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound represented by a formula:
wherein each ---- is independently an optional covalent bond, wherein valence is satisfied;
wherein R 1 , when present, is selected from C1-C12 alkyl and C1-C12 alkenyl;
wherein R 2 , when present, is selected from C1-C12 alkyl and C1-C12 alkenyl;
wherein R 7 is selected from hydrogen, hydroxyl, amino, and halogen; and
wherein R 8 is selected from hydrogen and C1-C6 alkyl;
or a pharmaceutically acceptable salt, solvate, or polymorph thereof.
14 . The composition of claim 13 , wherein the pharmaceutically acceptable carrier is a liposome.
15 . The composition of claim 14 , wherein the liposome comprises a phospholipid.
16 . The composition of claim 14 , wherein the liposome comprises one or more lipids selected from phosphatidylcholine, tocopherol, cholesterol, and 1,2-distearoyl-phosphatidyl ethanolamine-methyl-polyethyleneglycol conjugate.
17 . The composition of claim 14 , wherein the liposome comprises phosphatidylcholine and tocopherol.
18 . A kit comprising at least one compound represented by a formula:
wherein each ---- is independently an optional covalent bond, wherein valence is satisfied;
wherein R 1 , when present, is selected from C1-C12 alkyl and C1-C12 alkenyl;
wherein R 2 , when present, is selected from C1-C12 alkyl and C1-C12 alkenyl;
wherein R 7 is selected from hydrogen, hydroxyl, amino, and halogen; and
wherein R 8 is selected from hydrogen and C1-C6 alkyl;
or a pharmaceutically acceptable salt, solvate, or polymorph thereof, and one or more of:
a) at least one agent known to increase the likelihood of a parasitic disease in a mammal;
b) at least one agent known to decrease the likelihood of a parasitic disease in a mammal;
c) at least one agent known to treat a parasitic disease in a mammal; or
d) instructions for treating a parasitic disease.
19 . The kit of claim 18 , wherein the at least one compound and the at least one agent are co-formulated.
20 . The kit of claim 18 , wherein the at least one compound and the at least one agent are co-packaged.