| Popis: |
Background: There is a general lack of effective and economical chemotherapeutic agents for the treatment of widely prevalent leishmanias. To develop locally available, low cost alternative therapy, a series of diterpene lactones isolated from Suregada multiflora and their semisynthetic derivatives have been evaluated against the protozoan parasite Leishmania. Methods: A series of diterpene lactones were isolated from methanolic extract of Suregada multiflora. Major constituents were further derivatized through chemical and microbial transformations. Antileishmanial activity of structurally diverse diterpene lactones was performed by testing them in vitro against L. donovani promastigotes. All compounds were also tested for their cytotoxic effects by the brine shrimp bioassay. Results: Among all compounds evaluated in current studies, natural diterpenes Gelomulide A (1) and G (2) were found significantly active with IC50 values below 20µg/ml. While, among synthesized derivatives; compounds 5, 9 and 10 were found more potent with IC50 value 17.49, 18.38 and 17.81µg/ml, respectively. None of these compounds showed cytotoxic effects in the brine shrimp bioassay (LC50> 300). Conclusion: A new class of diterpene lactones was identified as potential antileshmanial agent. The structural diversity of natural and semisynthetic diterpene lactones, helped to rationalize structure– activity relationships. Activity of these diterpene lactones owed to C-8/14 epoxide along with unsubstituted C-1. Keto group at C-1 always lower the activity unless it is in α, β-unsaturated form. Presence of acetyl group at C-3 and 6 usually augmented the antileishmanila potential |
