title: Chemical composition of Aspidosperma ulei Markgr. and antiplasmodial activity of selected indole alkaloids.
abstract: A new indole alkaloid, 12-hydroxy-N-acetyl-21(N)-dehydroplumeran-18-oic acid (13), and 11 known indole alkaloids: 3,4,5,6-tetradehydro-β-yohimbine (3), 19(E)-hunteracine (4), β-yohimbine (5), yohimbine (6), 19,20-dehydro-17-α-yohimbine (7), uleine (10), 20-epi-dasycarpidone (11), olivacine (8), 20-epi-N-nor-dasycarpidone (14), N-demethyluleine (15) and 20(E)-nor-subincanadine E (12) and a boonein δ-lactone 9, ursolic acid (1) and 1D,1O-methyl-chiro-inositol (2) were isolated from the EtOH extracts of different parts of Aspidosperma ulei Markgr. (Apocynaceae). Identification and structural elucidation were based on IR, MS, ¹H- and ¹³C-NMR spectral data and comparison to literature data. The antiplasmodial and antimalarial activity of 1, 5, 6, 8, 10 and 15 has been previously evaluated and 1 and 10 have important in vitro and in vivo antimalarial properties according to patent and/or scientific literature. With the aim of discovering new antiplasmodial indole alkaloids, 3, 4, 11, 12 and 13 were evaluated for in vitro inhibition against the multi-drug resistant K1 strain of the human malaria parasite Plasmodium falciparum. IC₅₀ values of 14.0 (39.9), 4.5 (16.7) and 14.5 (54.3) mg/mL (mM) were determined for 3, 11 and 12, respectively. Inhibitory activity of 3, 4, 11, 12 and 13 was evaluated against NIH3T3 murine fibroblasts. None of these compounds exhibited toxicity to fibroblasts (IC₅₀ > 50 mg/mL). Of the five compounds screened for in vitro antiplasmodial activity, only 11 was active.
authors.affiliation: Instituto Nacional de Pesquisas da Amazônia, Caixa Postal 2223-CEP 69080-971, Manaus, Amazonas, Brasil.
authors.forename: Zelina Estevam
authors.initials: ZE
authors.lastname: dos Santos Torres
authors.forename: Edilberto Rocha
authors.initials: ER
authors.lastname: Silveira
authors.forename: Luiz Francisco
authors.initials: LF
authors.lastname: Rocha e Silva
authors.forename: Emerson Silva
authors.initials: ES
authors.lastname: Lima
authors.forename: Marne Carvalho
authors.initials: MC
authors.lastname: de Vasconcellos
authors.forename: Daniel Esdras
authors.initials: DE
authors.lastname: de Andrade Uchoa
authors.forename: Raimundo Braz
authors.initials: RB
authors.lastname: Filho
authors.forename: Adrian Martin
authors.initials: AM
authors.lastname: Pohlit
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D030009:Aspidosperma / Q000737:chemistry*; D026121:Indole Alkaloids / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D021261:Parasitic Sensitivity Tests; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects
chemical_list: D000962:Antimalarials; D026121:Indole Alkaloids; D010936:Plant Extracts