Five new cassane diterpenes from Myrospermum frutescens with activity against Trypanosoma cruzi.
Five novel cassane diterpenes (1-5) with activity against Trypanosoma cruzi were isolated from leaves of Myrospermum frutescens. The structures were determined as 18-hydroxycassan-13,15-diene (1), 6beta,18-dihydroxycassan-13,15-diene (2), 6beta-hydroxy-18-acetoxycassan-13,15-diene (3), 18-acetoxy-13,15-diene-19-cassanoic acid (4), and 6beta,13beta-dihydroxy-18-acetoxycassan-14(17),15-diene (5). Structures were elucidated by spectroscopic analysis (NMR and HRCIMS) and by the synthesis of derivatives 2a and 2b. Compounds 3 and 5 were more active against the extracellular form of the parasite (11 and 16 microM, respectively) than the intracellular forms, while compounds 1 and 2 were more active against the more clinically relevant intracellular forms of the parasite (17 microM). Compounds 1 and 2 were approximately 9-fold more toxic toward T. cruzi than toward human fibroblasts, the cell type that serves as the parasite's mammalian host cell.
Mendoza
Daniel Torres
DT
Laboratory of Natural Products, Faculty of Natural and Exact Sciences and Technology, Apartado 0824, University of Panama, Panama City, Republic of Panama.
Ureña González
Luis D
LD
Ortega-Barría
Eduardo
E
Capson
Todd L
TL
Rios
Luis Cubilla
LC
D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D007887:Fabaceae / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010176:Panama; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D013237:Stereoisomerism; D014344:Trypanocidal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects*
D004224:Diterpenes; D014344:Trypanocidal Agents