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-3β-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-3β-ol (7), ent-8(14),15-pimaradien-3β-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-3β-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.

Key words

leishmanicidal activity - cytotoxic activity - Leishmania amazonensis - pimaranes - Aldama arenaria (syn. Viguiera arenaria) - Asteraceae

Publikationsverlauf

Eingereicht: 23. August 2021

Angenommen nach Revision: 28. November 2021

Accepted Manuscript online:
28. November 2021

Artikel online veröffentlicht:
10. Februar 2022

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