In Vitro Cytotoxic and Leishmanicidal Activity of Isolated and Semisynthetic ent-Pimaranes from Aldama arenaria.

ABSTRACT

Two pimaranes ent-pimara-8(14),15-dien-19-oic acid (1 ) and ent-8(14),15-pimaradien-3ß-ol (2 ), isolated from Aldama arenaria, and six semi-synthetic derivatives methyl ester of the ent-pimara-8(14),15-dien-19-oic acid (3 ), ent-pimara-8(14),15-dien-19-ol (4 ), acetate of ent-pimara-8(14),15-dien-19-ol (5 ), ent-pimara-8(14),15-dien-19-ol succinic acid (6 ), acetate of ent-8(14),15-pimaradien-3ß-ol (7 ), ent-8(14),15-pimaradien-3ß-ol succinic acid (8 ) were evaluated in vitro for their cytotoxic activities to childhood leukemia cell lines and leishmanicidal activity against the parasite Leishmania amazonensis. Among these compounds, 1 to 6 presented moderate cytotoxic activity, with compound 4 being the most active (GI50 of 2.6 µM for the HL60 line) and the derivatives 7 and 8 being inactive. Against the parasite Leishmania amazonensis, the most promising derivative was the acetate of ent-pimara-8(14),15-dien-19-ol (5 ), with EC50 of 20.1 µM, selectivity index of 14.5, and significant reduction in the parasite load. Pimarane analogues 1 , ent-pimara-8(14),15-dien-19-oic acid, and 2 , ent-8(14),15-pimaradien-3ß-ol, presented different activities, corroborating the application of such molecules as prototypes for the design of other derivatives that have greater cytotoxic or leishmanicidal potential.