Activity-guided isolation of cytotoxic constituents from the bark of Aglaia crassinervia collected in Indonesia

Three new glabretal-type triperpenoids, aglaiaglabretols A–C, and nine known compounds, were isolated from the bark of Aglaia crassinervia. The cytotoxic activity of all isolates and several chemical transformation products was evaluated. The known cyclopenta[ b]benzofuran, rocaglaol, was found to be significantly cytotoxic and comparable in potency to the positive controls, paclitaxel and camptothecin. Aglaiaglabretol B ( 2) was further tested in an in vivo hollow fiber model. Activity-guided fractionation of a CHCl 3-soluble partition of the MeOH extract of the bark of Aglaia crassinervia collected in Indonesia led to the isolation of three new glabretal-type triterpenoids, aglaiaglabretols A–C ( 1– 3), as well as nine known compounds, 3- epi-cabraleahydroxylactone ( 4), cabraleahydroxylactone ( 5), rocaglaol ( 6), 2β,3β-dihydroxy-5α-pregn-17(20)-( E)-16-one, scopoletin, and mixtures of cabraleadiol and epicotillol and of β-sitosterol and stigmasterol. The structures of compounds 1– 3 were determined on the basis of spectroscopic and chemical methods. The structure of aglaiaglabretol A ( 1) was confirmed by single-crystal X-ray analysis, and the absolute stereochemistry of this isolate was established by the Mosher ester method. The cytotoxic activity of all isolates and several chemical transformation products obtained in the present study was evaluated. The known cyclopenta[ b]benzofuran, rocaglaol ( 6), was found to be significantly active and comparable in potency to the positive controls, paclitaxel and camptothecin. Aglaiaglabretol B ( 2) was further tested in an in vivo hollow fiber model.