Leishmania inhibitors
In one aspect, methods and compositions for treating parasitic diseases, for example, leishmaniasis.
1. A pharmaceutical composition comprising a therapeutically effective amount of a compound, and a pharmaceutically acceptable carrier to treat an infection, wherein the compound has a structure represented by formula (I) or formula (II):
wherein R 1 , R 2 , and R 5 are independently selected from the group consisting of hydrogen, unsubstituted C 1 -C 6 alkyl, unsubstituted C 1 -C 6 alkyl halide, unsubstituted C 1 -C 6 alkoxy, unsubstituted C 1 -C 6 ester, and unsubstituted C 1 -C 6 alkylamine;
R 1a and R 10 are independently selected from the group consisting of hydroxyl, amine, halogen, unsubstituted C 1 -C 6 alkyl halide, unsubstituted C 1 -C 6 alkoxy, unsubstituted C 1 -C 6 ester, and unsubstituted C 1 -C 6 alkylamine;
R 1b and R 2a are independently selected from the group consisting of hydrogen, hydroxyl, amine, halogen, unsubstituted C 1 -C 6 alkyl, unsubstituted C 1 -C 6 alkyl halide, unsubstituted C 1 -C 6 alkoxy, unsubstituted —OC(O)C 2 -C 5 , unsubstituted —C(O)OC 1 -C 5 , and unsubstituted C 1 -C 6 alkylamine;
R 3 and R 4 are independently, for each occurrence, selected from the group consisting of hydrogen, unsubstituted C 1 -C 6 alkyl, unsubstituted C 1 -C 6 ester, or R 3 and R 4 combine together with the atom to which they are attached to form a carbonyl;
R 3a and R 4a are independently selected from the group consisting of hydrogen, hydroxyl, unsubstituted C 1 -C 10 alkyl, unsubstituted C 1 -C 10 alkenyl, unsubstituted C 1 -C 10 ester, or R 3a and R 4a combine together with the atoms to which they are attached to form a carbonyl;
R 6 is selected from the group consisting of hydrogen, hydroxyl, unsubstituted C 1 -C 6 alkyl, unsubstituted C 1 -C 6 alkyl halide, unsubstituted C 1 -C 6 alkoxy, unsubstituted C 1 -C 6 ester, and unsubstituted C 1 -C 6 alkylamine;
R 7 is selected from the group consisting of hydrogen, hydroxyl, unsubstituted C 2 -C 6 alkyl, unsubstituted C 1 -C 6 alkyl halide, unsubstituted C 1 -C 6 alkoxy, unsubstituted —OC(O)C 2 -C 5 , unsubstituted —C(O)OC 1 -C 5 , and unsubstituted C 1 -C 6 alkylamine;
R 7a is selected from the group consisting of hydrogen, hydroxyl, unsubstituted C 1 -C 6 alkyl, unsubstituted C 1 -C 6 alkyl halide, unsubstituted C 1 -C 6 alkoxy, unsubstituted C 1 -C 6 ester, and unsubstituted C 1 -C 6 alkylamine; or
R 6 and R 7 combine together with the atoms to which they are attached form a substituted C 5 -C 8 cycloalkyl, a substituted C 5 -C 8 cycloalkenyl, or a substituted C 5 -C 8 heterocycle, wherein the substituents include carbonyl and one or more of hydroxyl, unsubstituted C 2 -C 6 alkyl, unsubstituted C 1 -C 6 alkoxy, unsubstituted C 1 -C 6 ester, and unsubstituted C 1 -C 6 alkylamine;
R 9 and R 11 are independently selected from the group consisting of hydrogen, unsubstituted C 1 -C 6 alkyl, unsubstituted C 1 -C 6 alkyl halide, unsubstituted C 1 -C 6 alkoxy, unsubstituted C 1 -C 6 ester, and unsubstituted C 1 -C 6 alkylamine; and
R 12 is selected from the group consisting of hydrogen, hydroxyl, amine, halogen, cyano, nitro, unsubstituted C 1 -C 6 alkyl, unsubstituted C 1 -C 6 alkyl halide, unsubstituted C 1 -C 6 alkoxy, unsubstituted C 1 -C 6 ester, and unsubstituted C 1 -C 6 alkylamine; and
represents a bond that is present or absent.
2. The pharmaceutical composition of claim 1 , wherein the compound has a formula (I-A):
wherein R 8 is selected from the group consisting of hydroxyl, unsubstituted C 2 -C 6 alkyl, unsubstituted C 1 -C 6 alkyl halide, unsubstituted C 1 -C 6 alkoxy, unsubstituted C 1 -C 6 ester, and unsubstituted C 1 -C 6 alkylamine.
3. The pharmaceutical composition of claim 1 , wherein the compound has a formula (I-B):
wherein R 6 is selected from the group consisting of hydroxyl, unsubstituted C 1 -C 6 alkyl, unsubstituted C 1 -C 6 alkyl halide, unsubstituted C 1 -C 6 alkoxy, unsubstituted C 1 -C 6 ester, and unsubstituted C 1 -C 6 alkylamine;
R 7 is selected from the group consisting of hydroxyl, unsubstituted C 2 -C 6 alkyl, unsubstituted C 1 -C 6 alkyl halide, unsubstituted C 1 -C 6 alkoxy, unsubstituted —OC(O)C 2 -C 5 , unsubstituted —C(O)OC 1 -C 5 , and unsubstituted C 1 -C 6 alkylamine.
4. The pharmaceutical composition of claim 3 , wherein R 6 is selected from unsubstituted C 1 -C 6 alkyl.
5. The pharmaceutical composition of claim 1 , wherein R 1 , R 2 , and R 5 are independently selected from the group consisting of unsubstituted C 1 -C 6 alkyl and unsubstituted C 1 -C 6 alkoxy.
6. The pharmaceutical composition of claim 1 , wherein the compound has a structure represented by formula (II-A):
wherein R 1a and R 10 are independently, for each occurrence, selected from the group consisting of hydroxyl, amine, halogen, unsubstituted C 1 -C 6 alkyl halide, unsubstituted C 1 -C 6 alkoxy, unsubstituted C 1 -C 6 ester, and unsubstituted C 1 -C 6 alkylamine;
R 4a is selected from the group consisting of unsubstituted C 1 -C 10 alkyl, unsubstituted C 1 -C 10 alkenyl, or unsubstituted C 1 -C 10 ester.
7. The pharmaceutical composition of claim 1 , wherein R 1a , R 1b , and R 10 are independently selected from the group consisting of hydroxyl, amine, halogen, C 1 -C 6 alkoxy, OC(O)C 2 -C 5 , and —C(O)OC 1 -C 5 .
8. The pharmaceutical composition of claim 1 , wherein R 12 is selected from the group consisting of hydroxyl, amine, halogen, cyano, and nitro.
9. A pharmaceutical composition to treat an infection comprising a therapeutically effective amount of a compound according to claim 1 or a compound having a structure below, and a pharmaceutically acceptable carrier selected from the group consisting of a cream, gel, liposome, nanoparticle, ointment, a tablet, capsule, or suppository:
10. A method of treating an infection comprising: delivering to a subject in need thereof, a pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition comprises a therapeutically effective amount of a compound having a structure represented by formula (I) or formula (II), and a pharmaceutically acceptable carrier, to treat the infection, wherein the infection is a parasitic infection associated with a Leishmania sp.
11. The method of claim 10 , wherein the compound has a formula (I-A):
wherein R 8 is selected from the group consisting of hydroxyl, unsubstituted C 2 -C 6 alkyl, unsubstituted C 1 -C 6 alkyl halide, unsubstituted C 1 -C 6 alkoxy, unsubstituted C 1 -C 6 ester, and unsubstituted C 1 -C 6 alkylamine.
12. The method of claim 10 , wherein the compound has a formula (I-B):
wherein R 6 is selected from the group consisting of hydroxyl, unsubstituted C 1 -C 6 alkyl, unsubstituted C 1 -C 6 alkyl halide, unsubstituted C 1 -C 6 alkoxy, unsubstituted C 1 -C 6 ester, and unsubstituted C 1 -C 6 alkylamine;
R 7 is selected from the group consisting of hydroxyl, unsubstituted C 2 -C 6 alkyl, unsubstituted C 1 -C 6 alkyl halide, unsubstituted C 1 -C 6 alkoxy, unsubstituted OC(O)C 2 -C 5 , unsubstituted —C(O)OC 1 -C 5 , and unsubstituted C 1 -C 6 alkylamine.
13. The method of claim 10 , wherein R 6 is selected from unsubstituted C 1 -C 6 alkyl.
14. The method of claim 10 , wherein R 1 , R 2 , and R 5 are independently selected from the group consisting of unsubstituted C 1 -C 6 alkyl, unsubstituted C 1 -C 6 alkoxy.
15. The method of claim 10 , wherein the compound has a structure represented by formula (II-A):
wherein R 1a and R 10 are independently, for each occurrence, selected from the group consisting of hydroxyl, amine, halogen, unsubstituted C 1 -C 6 alkyl halide, unsubstituted C 1 -C 6 alkoxy, unsubstituted C 1 -C 6 ester, and unsubstituted C 1 -C 6 alkylamine;
R 4a is selected from the group consisting of unsubstituted C 1 -C 10 alkyl, unsubstituted C 1 -C 10 alkenyl, or unsubstituted C 1 -C 10 ester.
16. A method of treating an infection comprising: delivering to a subject in need thereof, a pharmaceutical composition according to claim 9 .
17. The method of claim 10 , wherein the parasitic infection is associated with Leishmania donovani.
18. The method of claim 10 , wherein the subject is a mammal.