ANTIPLASMODIAL AND ANTICANCER PRINCIPLES FROM MILLETTIA DURA, MILLETTIA LEUCANTHA AND MILLETTIA LASIANTHA

Description

Despite all efforts in the fight against malaria and cancer, the number of infections per year is still high or even rising for cancer, making them the leading causes of fatelity 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 M. dura, M. leucantha and M. lasiantha species from Kenya. The compounds were isolated using column chromatography on silica gel 60 (60-120 mesh) plus Sephadex LH-20. Purification was done on a Chromatotron (7924T, 24V, 200rev/min). Compounds were characterized basing on NMR, MS, UV and IR spectral data. A total of 51 compounds where isolated and characterized. The first phytochemical study on the flowers of M. dura yielded nine compounds, of which, 4,2¢-dihydroxy-4¢-methoxychalcone was appearing for the first time in the genus. Seven compounds were isolated from the pods while thirteen compounds were got from the stem bark. The presence of deguelin and tephrosin in the stem bark of M. dura was a unique finding. The four flavonoids, chrysin, apigenin, chrysin 7-O-?-D-glucoside, genkwanin from M. leucantha (leaves) are being reported for the first time from the genus, meanwhile, the root bark M. leucantha yielded six compounds. The leaves of M. lasiantha, gave four flavones, the stem bark gave four compounds, while out ot the four compounds isolated from the roots, 3,8-dihydroxy-7,9-dimethoxycoumestan and 7,5?-dihydroxy-6?,4?-dimethoxycoumaronochromone are novel compounds. Out of the samples screened against 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 ?g/ml respectively, while the most active compound was milletone with respective IC₅₀’s of 33.1±3.7 and 27.4±3.1 ?M. Out of the fifteen flavonoids tested for cytotoxicity, tephrosin and durmillone were the most active with respective 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 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. Presence of millettone and millettosine only in the seedpods of M. dura distinguishes this taxon from M. ferruginea, supporting the morphological difference in their pods.