In vitro antiplasmodial activity and cytotoxicity of extracts and fractions of Vitex madiensis, medicinal plant of Gabon.

Vitex madiensis Oliv. (Lamiaceae) is traditionally used to treat malaria symptoms in Haut-Ogooué, Gabon. Leaves and stem barks extracts were obtained using dichloromethane (CH(2)Cl(2)), ethyl acetate (EtOAc) and methanol (MeOH) as extraction solvents and fractionated on silica gel column. The in vitro antiplasmodial activity of CH(2)Cl(2), EtOAc and MeOH extracts and fractions was evaluated against the chloroquine-resistant FCB strain and field isolates of Plasmodium falciparum using the DELI test. The cytotoxicity of the extracts was tested on MRC-5 and THP1 cells using the tetrazolium salt MTT colorimetric assay, and the selectivity index (SI) of each extract was calculated. CH(2)Cl(2) extract, the EA1 fraction from EtOAc extract of stem barks and cyclohexane (L(cycl)), dichloromethane (L(DM)) and butanol (L(but)) fractions from MeOH/H(2)O extract of leaves exhibited the highest in vitro antiplasmodial activity on FCB strain and field isolates (IC(50) from 0.53 to 4.87 µg/ml) with high selectivity index (of 20.15-1800). These data support the use of V. madiensis in malaria treatment along with continued investigations within traditional medicines in the search of new antimalarial agents. The EA1, C(6)H(12) and CH(2)Cl(2) fractions could be selected for future investigation or/and for the treatment of malaria symptoms after standardization.

Synthesis and cytotoxic activity of benzophenanthrolinone analogues of acronycine.

Condensation of either 2-bromobenzoic acid (4) or 2-chloro-3-nitrobenzoic acid (5) with suitable aminoquinolines 6-8 afforded phenylquinolylamines 9-13. Acid mediated cyclization gave the corresponding 12H-benzo[b][1,7]phenanthrolin-7-ones 14 and 15, and 12H-benzo[b][1,10]phenanthrolin-7-ones 16-18. Compounds 14, 16, and 17 were subsequently N-methylated to 6-demethoxyacronycine and acronycine analogues 19-21, whereas reduction of the aromatic nitro group of 18 gave the amino derivative 22. Unsubstituted 12H-benzo[b][1,10]phenanthrolin-7-ones 16, 17, 20, and 21 were devoid of significant cytotoxic activity, whereas 18 and 22, bearing a nitrogen substituent at position 11, were significantly active. Unsubstituted 12H-benzo[b][1,7]phenanthrolin-7-ones 14 and 19, which include a pyridine nitrogen in the same 4-position as the pyran oxygen of acronycine exhibited cytotoxic activities within the same range of magnitude as acronycine itself.