Phytochemical Investigation Of Three Leguminosae Plants For Cancer Chemopreventive Agents

Abstract

Cancer is one of the largest single and common causes of death in humans around the world. It is estimated to have claimed up to 8.2 million lives in the year 2012 and with an incidence of 14.1 million new cases. Plant metabolites such as flavonoids have been reported to display cancer chemopreventive properties such as anti-oxidant, anti-estrogenic effects and cytotoxicity. Three Leguminosae plants, Platycelphium voёnse, Millettia usaramensis subsp. usaramensis and Flemingia grahamiana, were phytochemically investigated to give a range of flavonoid derivatives, two triterpenoids and an anthraquinone. Twenty three of the isolated compounds are new and their structures were established using a combination of techniques including NMR, UV, CD and MS. From the stem bark of Platycelphium voёnse twelve compounds, including seven isoflavanones, one isoflavone, two 3-methoxyflavones and two triterpenes, were isolated and identified. Five of the isoflavanones including platyisoflavanones A (163) and C (166) are new. Similar investigation of the root bark of Millettia usaramensis subsp. usaramensis resulted in the isolation of thirteen compounds including two new flavanone derivatives: (2R,3R)-4'-O-geranyl-7-hydroxyflavanonol (179) and (S)-4'-O-geranyl-7-hydroxyflavanone (180) in addition to seven known 12a-hydroxyrotenoids, two isoflavones, one chalcone and a cinnamoyl alcohol derivative. From the roots of Flemingia grahamiana, seven isoflavones and five prenylated flavanones, including a new flavanone derivative, 5,3',4'-trihydroxy-8-,-dimethylallyl-2'',2''-dimethylpyrano-[5'',6'':6,7]-flavanone (191), along with a chromone and a gallocatechin derivative were obtained. Exposure of 8-(,-dimethylallyl)-2'',2''-dimethylpyrano-[5'',6'':6,7]-flavanones to deuterated dimethylsulfoxide led to isomerization of the flavones yielding the corresponding 6-,-dimethylallyl-2''',2'''-dimethylpyrano-[5''',6''':8,7]-flavanone isomers. This is the first report of such rearrangement. From the leaves of F. grahamiana, a range of flavonoids were isolated and identified. These included the known chalcone, flemingin A (196) and eleven new chalcones [including flemingin G (197)], two new flavanones and two new Z-aurones [such as flemingiaurone A (211)]. Five rotenoids, one triterpene, one isoflavanone and two chalcones were active against the MCF-7 human breast cancer cell line. Compounds 163 and 196 were cytotoxic against Vero cells and both were active against Mycobacterium tuberculosis. Compound 196 and four other chalcones exhibited strong radical scavenging activity against DPPH. Attempt to synthesize 2,5,2′-trihydroxy-4′,5′-dimethoxychalcone from 2-hydroxy-4,5-dimethoxyacetophenone and 2,5-diallyloxybenzaldehyde in the presence of KOH/methanol led to the formation of 2,5-diallyloxy-2′-hydroxy-4′,5′-dimethoxychalcone. Deprotection of the allyl groups using Pd(PPh3)4, prepared in-situ, in the presence of K2CO3/methanol, yielded a partially deprotected, 5-allyloxy-2,2′-dihydroxy-4′,5′-dimethoxychalcone.