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

Planta Med DOI: 10.1055/a-1708-2081Two 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. [...] Georg Thieme Verlag KG RÃ...

Source: Planta Medica - November 28, 2021 Category: Drugs & Pharmacology Authors: de Oliveira, Adriana da Silva Santos Conrado, Gabrielly Galdino Grazzia, Nathalia Miguel, Danilo Ciccone Franchi J únior, Gilberto Carlos Garcia, Vera L úcia Tags: Original Papers Source Type: research