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

Two pimaranes ent -pimara-8(14),15-dien-19-oic acid ( 1 ) and ent -8(14),15-pimaradien-3 beta -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-3 beta -ol ( 7 ), ent -8(14),15-pimaradien-3 beta -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 (GI (50) of 2.6 mu M 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 EC (50) of 20.1 mu M, 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-3 beta -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.

Automated summary

Two pimarane analogues and their derivatives isolated from Aldama arenaria exhibited moderate cytotoxic activity and leishmanicidal activity. Compound 4 showed the strongest cytotoxic activity, while derivative 5 showed the most promising leishmanicidal activity.