Antileishmanial activity and cytotoxicity of ent-beyerene diterpenoids
Murillo, Jilmar A.
Universidad de Antioquia
Gil, Juan F.
Universidad de Antioquia
Upegui, Yulieth A.
Universidad de Antioquia
Restrepo, Adriana M.
Universidad de Antioquia
Robledo, Sara M.
Universidad de Antioquia
Quinones, Winston
Universidad de Antioquia
Echeverri, Fernando
Universidad de Antioquia
Olivo, Horacio F.
University of Iowa
Escobar, Gustavo
Universidad de Antioquia
Journal
Bioorganic and Medicinal Chemistry
ISSN
0968-0896
1464-3391
Open Access
closed
Volume
27
Start page
153
End page
160
We describe the in vitro activity of two natural isomeric ent-beyerene diterpenes, several derivatives and synthetic intermediates. Beyerenols 1 and 2 showed EC50 of 4.6 +/- 9.4 and 5.3 +/- 9.4 mu g/mL against amastigotes of L. (V) brazilensis, with SI of 5.1 and 7.7, respectively. Beyerenol 1 was synthesized from stevioside. In vivo experiments with bereyenols showed cure in 50% of hamsters infected with L. (V) brazilensis topically applied as Cream I (beyerenol 1, 0.81%, w/w) and Cream III (beyerenol 2, 1.96%, w/w). These results suggest that beyerenols are potential candidates for cutaneous leishmaniasis chemotherapy by topical application. In vitro assays of amastigotes of L. (V) brazilensis showed EC50 of 1.1 +/- 0.1 and 1.3 +/- 0.04 mu g/mL, with SI of 3.1 and 3.5 for hydrazone intermediates 10 and 11, respectively.