A new antimalarial quassinoid from Simaba orinocensis.

Abstract

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 (IC(50) 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 (IC(50) 10 vs 2.3 microg/mL) and HL-60 (IC(50) 0.7 vs 0.025 microg/mL), respectively. In addition, 2 was >46- and >31-fold more potent than pentamidine and amphotericin B (IC(50) 0.035 vs 1.6 and 1.1 microg/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 (IC(50) 0.8-1.9 vs 0.3-1.0 microg/mL) against these cells.

• Authors: Ilias Muhammad, Erdal Bedir, Shabana I Khan, Babu L Tekwani, Ikhlas A Khan, Satoshi Takamatsu, Jerry Pelletier, Larry A Walker
• Journal: Journal of natural products (J Nat Prod) Vol. 67 Issue 5 Pg. 772-7 (May 2004) ISSN: 0163-3864 [Print] United States
• PMID: 15165136 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Antineoplastic Agents, Phytogenic
• Quassins
• orinocinolide
• simalikalactone D

Topics

• Animals
• Antimalarials (chemistry, isolation & purification, pharmacology)
• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Drug Screening Assays, Antitumor
• Humans
• Inhibitory Concentration 50
• Molecular Structure
• Peru
• Plants, Medicinal (chemistry)
• Plasmodium falciparum (drug effects)
• Quassins (chemistry, isolation & purification, pharmacology)
• Simaroubaceae (chemistry)
• Tumor Cells, Cultured