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

Author(s)

Santos de Oliveira, Adriana da Silva ; Conrado, Gabrielly Galdino ; Grazzia, Nathalia ; Miguel, Danilo Ciccone ; Franchi Junior, Gilberto Carlos ; Garcia, Vera Lucia

• Document type: Journal article
• Source: Planta Medica; v. 88, n. 13, p. 12-pg., 2022-02-10.

Abstract

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. (AU)

• FAPESP's process: 10/51454-3 - Morphoanatomical, metabolomic and molecular studies as subsidies to the systematic of Asteraceae species and access to their pharmacological potential
• Grantee: Beatriz Appezzato da Glória
• Support Opportunities: Research Projects - Thematic Grants