Derivatization Of Polygonum Senegalense Chalcones, Phytochemical Investigation Of Surface Exudates Of Tarchonanthus Camphoratus And Bioactivities Of The Compounds

Abstract

A number of compounds from medicinal plants have been reported to have biological activity against a wide range of disease causing agents. However, a majority of them have not been adopted for conventional use mainly due to their low therapeutic Index (TI) relative to WHO minimum acceptable standards. There is need for retrieval or re-isolation of these moderately active principles and modify their functionality through synthesis in order to optimize their activities. Moreover, research shows that most of the commercial drugs are semi-synthetic. The flavonoids of Polygonum senegalense, for instance, have been found to have mild anti-plasmodial activity. This research led to diversification of four chalcones and two flavones isolated from P. senegalense and T. camphoratus to yield pyrazolines pyrazole, isoxazolines, oximes and pyrimidine templates. The products of the syntheses include 2-(4, 5-dihydro-1,5-diphenyl-1H-pyrazol-3-yl)-3,5-dimethoxyphenol (74), 2-(4,5-dihydro-1,5-diphenyl-1H-pyrazol-3-yl)-3,5dimethoxybenzene-1,4-diol (75), 4-(4,5-dihydro-1,5-diphenyl-1H-pyrazol-3-yl)-5-methoxybenzene-1,3-diol (76), 4-(4,5-dihydro-1,5-diphenyl-1H-pyrazol-3-yl)-2,5-dimethoxybenzene-1,3-diol (77), 2-(4,5-dihydro-5-phenyl-1H-pyrazol-3-yl)-3,5-dimethoxybenzene-1,4-diol (79), 2-(4,5-dihydro-5-phenyl-1H-pyrazol-3-yl)-3,5-dimethoxyphenol (80), 2-(4,5-dihydro-5-phenyl-1H-pyrazol-3-yl)-5-methoxybenzene-1,3-diol (81), 1-(4,5-dihydro-3-(3,6-dihydroxy-2,4-dimethoxyphenyl)-5-phenylpyrazol-1-yl)ethanone (82), 1-(4,5-dihydro-3-(2-hydroxy-4,6-dimethoxyphenyl)-5-phenylpyrazol-1-yl)ethanone, 2-(4,5-dihydro-5-phenylisoxazol-3-yl)-3,5-dimethoxyphenol (83), 5-methoxy-2-(5-(2,3,4,5-tetramethoxyphenyl)-1H-pyrazol-3-yl)benzene-1,3-diol (84), 4-(4,5-dihydro-5-phenylisoxazol-3-yl)-5-methoxybenzene-1,3-diol (85), 2-(-4,5-dihydro-5-phenylisoxazol-3-yl)-3,5- viii dimethoxyphenol (86), one oxime derivative (87) and one bypyrimidine derivative 4,5-dihydro-6-(2,4-dihydroxy-3,6-dimethoxyphenyl)-4-phenylpyrimidine-2-(1H)-thione (88) . Besides, four flavonoids and three terpenoids were isolated from T. camphoratus. The terpenoids are 2,3,3a,4,5,7a-hexahydro-7a-methyl-4-methylene-1H-inden-5-ol (61), (Z)-3a,4,7,8,9,9a-hexahydro-6a-methyl-3,4-dimethyleneazuleno[4,5-b]furan-2(3H,6aH,9bH)-one (62) and (-)-parthenolide (63) with the last two being novel. The four flavonoids are 5,7-dihydroxy-2-(4-hydroxyphenyl)-6-methoxy-4H-chromen-4-one (65) and ,7-dihydroxy-2-(3,4-dihydroxyphenyl)-6-methoxy-4H-chromen-4-one (66), 5,7-dihydroxy-2-(3,4-Dihydroxyphenyl)-4H-chromen-4-one (62) 5,7-dihydroxy-2-(4-hydroxyphenyl)-6-methoxy-4H-chromen-4-one (65) and ,7-dihydroxy-2-(3,4-dihydroxyphenyl)-6-methoxy-4H-chromen-4-one (66), 5,7-di hydroxy-2-(3,4-dihydroxyphenyl)-4H-chromen-4-one (62). The structures of both natural and semi-synthetic compounds were determined by Nuclear Magnetic Resonance Spectroscopy (NMR) and ESIHRMS spectroscopic techniques. All compounds were tested for anti- plasmodial anti-fungal, anti-bacterial, anti-leishmanial activity and found to have insignificant activity against standard strains of malaria, fungal, leishmania and bacterial organisms.