Diterpenoid membranolide compounds having anti-leishmania activity and uses thereof
In a screening program, the Antarctic sponge Dendrilla membranosa was found to produce diterpenoid secondary metabolites with activity against the leishmaniasis-causing parasite Leishmania donovani . The present invention concerns compositions useful for control of Leishmania spp. parasites in vitro and in vivo and treatment of leishmaniasis; methods for treatment of leishmaniasis; and methods for controlling Leishmania spp. parasites in vitro and in vivo.
1. A composition comprising at least one anti- Leishmania agent; and at least one other compound having the following chemical structure:
or a pharmaceutically acceptable salt thereof; or,
or a pharmaceutically acceptable salt thereof.
2. The composition of claim 1 , wherein the at least one anti- Leishmania agent is an antimonial, amphotericin B, miltefosine, pentamidine, aminoglycoside-amino-cyclitol antibiotic, azole, 4-methyl-6-methoxy-8-aminoquinoline, or nucleoside analogue, or a combination thereof.
3. The composition of claim 1 , wherein the at least one other compound has the following chemical structure:
or a pharmaceutically acceptable salt thereof.
4. The composition of claim 3 , wherein the at least one anti- Leishmania agent is an antimonial, amphotericin B, miltefosine, pentamidine, aminoglycoside-amino-cyclitol antibiotic, azole, 4-methyl-6-methoxy-8-aminoquinoline, or nucleoside analogue, or a combination thereof.
5. The composition of claim 1 , wherein the at least one other compound has the following chemical structure:
or a pharmaceutically acceptable salt thereof.
6. The composition of claim 5 , wherein the at least one anti- Leishmania agent is an antimonial, amphotericin B, miltefosine, pentamidine, aminoglycoside-amino-cyclitol antibiotic, azole, 4-methyl-6-methoxy-8-aminoquinoline, or nucleoside analogue, or a combination thereof.
7. The composition of claim 1 , wherein the at least one other compound comprises a compound having the chemical structure:
or a pharmaceutically acceptable salt thereof; and a compound having the chemical structure:
or a pharmaceutically acceptable salt thereof.
8. The composition of claim 7 , wherein the at least one anti- Leishmania agent is an antimonial, amphotericin B, miltefosine, pentamidine, aminoglycoside-amino-cyclitol antibiotic, azole, 4-methyl-6-methoxy-8-aminoquinoline, or nucleoside analogue, or a combination thereof.