A new antimalarial quassinoid from Simaba orinocensis

A new antimalarial quassinoid, namely, orinocinolide (1), was isolated from the root bark of Simaba orinocensis, together with the previously reported simalikalactone D (2). The structure of 1 was determined primarily from 1D and 2D NMR analysis, as well as by chemical derivatization. Compound 1 was found to be as equally potent as 2 against Plasmodium. falciparum clones D6 and W2 (IC50 3.27 and 8.53 ng/mL vs 3.0 and 3.67 ng/mL, respectively), but was 4- and 28-fold less toxic than 2 against VERO cells (IC50 10 vs 2.3 mug/mL) and HL-60 (IC50 0.7 vs 0.025 mug/mL), respectively. In addition, 2 was >46- and >31-fold more potent than pentamidine and amphotericin B (IC50 0.035 vs 1.6 and 1.1 mug/mL) against Leishmania donovani, while 1 was inactive. Orinocinolide (1) inhibited growth of human cancer cells SK-MEL, KB, BT-549, and SK-OV-3, but was less potent than 2 (IC50 0.8-1.9 vs 0.3-1.0 mug/mL) against these cells.