Antiplasmodial and Anticancer Principles From Millettia Dura, Millettia Leucantha and Millettia Lasiantha

Abstract

Despite all the undertakings to fight malaria and cancer, the infections occurrencies per year is still high or even rising as the case for cancer, making them the leading causes of fatality in the world. The Plasmodium resistance and varied side effects of the conventional cancer drugs is a major hitch in the treatment of malaria and cancer, hence posing a big challenge to the global health care. Phytochemicals from higher plants have produced safe antimalarials and anticancers and still offer hope for new drugs. The aim of this study therefore was to search for anticancer and antimalarial principles from Millettia dura, Millettia leucantha and Millettia lasiantha from Kenya. The compounds were isolated using column chromatography over silica gel 60 (60-120 mesh) plus Sephadex LH-20. Purification was done on a Chromatotron (7924T, 24V, 200 rpm). Compounds were characterized basing on NMR, MS, UV and IR spectral data. A total of 51 compounds were isolated and characterized. The first phytochemical study on the flowers of M. dura yielded nine compounds, this being the first report of 4,2-dihydroxy-4-methoxychalcone (228) from the genus. Seven compounds were isolated from the pods while thirteen compounds were gotten from the stem bark. The presence of deguelin (170) and tephrosin (171) in the stem bark of M. dura was a unique finding. This is also the first report of the four flavonoids, chrysin (229), apigenin (230), chrysin 7-O-β-D-glucoside (231) and genkwanin (232) from the genus isolated from M. leucantha (leaves), meanwhile, the root bark yielded six compounds. This is the primary phytochemical study on M. lasiantha which gave four flavones from its leaves, four compounds from the stem bark, while out ot the four compounds isolated from the roots, 3,8-dihydroxy-7,9-dimethoxycoumestan (241) and 7,5′-dihydroxy-6′,4′-dimethoxycoumaronochromone (242) are novel compounds. Out of the samples screened againest W2 and D6 strains of P. falcipalum, the stem bark extract had the highest activity of 31.9±8.6 and 23.1±4.5 μg/ml againest W2 and D6 respectively, while the most active compound was milletone (172) with respective IC50’s of 33.1±3.7 and 27.4±3.1 μM againest W2 and D6. Out of the fifteen flavonoids tested for cytotoxicity, tephrosin (171) and durmillone (99) were the most active with respective strong IC50’s of 3.14 and 6.6 ±1.2 μM against A549 cancer cell line. Chemotaxonomic review of M. dura and its morphologically related M. ferruginea showed both taxa to elaborate mainly isoflavones (33 reported) out of which 23 have C-8 prenyl group or its modification as 2,2-dimethylchromene moety at C-7/C-8 and 91% of the isoflavones are 5-deoxygenated. Oxygenation at C-8 has been reported only in M. dura. Millettone

(172) and millettosine (173) only identified in the seedpods of M. dura could be responsible for the morphological difference observed in the seed pods of the two taxa and serves to distinguish M. dura from M. ferruginea.