title: 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.affiliation: Departments of Pharmacognosy and Pharmacology, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, Mississippi 38677, USA. milias@olemiss.edu
authors.forename: Ilias
authors.initials: I
authors.lastname: Muhammad
authors.forename: Erdal
authors.initials: E
authors.lastname: Bedir
authors.forename: Shabana I
authors.initials: SI
authors.lastname: Khan
authors.forename: Babu L
authors.initials: BL
authors.lastname: Tekwani
authors.forename: Ikhlas A
authors.initials: IA
authors.lastname: Khan
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takamatsu
authors.forename: Jerry
authors.initials: J
authors.lastname: Pelletier
authors.forename: Larry A
authors.initials: LA
authors.lastname: Walker
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010568:Peru; D010946:Plants, Medicinal / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000187:drug effects*; D036702:Quassins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D029641:Simaroubaceae / Q000737:chemistry*; D014407:Tumor Cells, Cultured
chemical_list: D000962:Antimalarials; D000972:Antineoplastic Agents, Phytogenic; D036702:Quassins; C487000:orinocinolide; C024970:simalikalactone D