Bioactive 4-phenylcoumarins from Mesua Elegans and Mesua Kunstleri / Chan Gomathi

Chan, Gomathi (2015) Bioactive 4-phenylcoumarins from Mesua Elegans and Mesua Kunstleri / Chan Gomathi. PhD thesis, University of Malaya.

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Abstract

Phytochemical analyses on the bark of two Clusiaceae plants, Mesua elegans and Mesua kunstleri, were carried out. Twenty-four compounds were successfully isolated using several chromatographic techniques; column chromatography (CC), thin layer chromatography (TLC), preparative thin layer chromatography (PTLC), centrifugal partition chromatography (CPC) and high performance liquid chromatography (HPLC). The structures of the isolated compounds were elucidated using various spectroscopic methods; 1D-NMR (1H, 13C and DEPT), 2D-NMR (COSY, HSQC, HMBC and NOESY), UV, IR, HRESIMS and by comparison with data from the literature. A total of twenty-two compounds were isolated from M. elegans, namely mammea A/BA 28, 5,7-dihydroxy-8-(2-methylbutanoyl)-6-[(E)-3,7-dimethylocta-2,6-dienyl]-4- phenyl-2H-chromen-2-one 47, 5,7-dihydroxy-8-(3-methylbutanoyl)-6-[(E)-3,7- dimethylocta-2,6-dienyl]-4-phenyl-2H-chromen-2-one 48, mammea A/BB 55, mammea A/BA cyclo D 187, mesuagenin A 189, mesuagenin B 190, mesuagenin C 191, ochrocarpin E 192, mammea A/BB cyclo F 193, mammea A/BA cyclo F 194, mesuagenin F 195, mesuagenin D 196, isodisparfuran 197, mesuagenin G 198, mesuagenin H 199, mesuagenin I 200, mesuagenin J 201, mesuagenin K 202, mesuagenin L 203, mesuagenin M 204 and mesuagenin N 205, of which thirteen are new; mesuagenin A 189, mesuagenin B 190, mesuagenin C 191, mesuagenin F 195, mesuagenin D 196, mesuagenin G 198, mesuagenin H 199, mesuagenin I 200, mesuagenin J 201, mesuagenin K 202, mesuagenin L 203, mesuagenin M 204 and mesuagenin N 205. iii From M. kunstleri, a total of ten compounds were isolated, which are mammea A/BA 28, 5,7-dihydroxy-8-(2-methylbutanoyl)-6-[(E)-3,7-dimethylocta-2,6-dienyl]-4-phenyl- 2H-chromen-2-one 47, 5,7-dihydroxy-8-(3-methylbutanoyl)-6-[(E)-3,7-dimethylocta- 2,6-dienyl]-4-phenyl-2H-chromen-2-one 48, mammea A/BB 55, mammea A/BB cyclo D 186, mammea A/BA cyclo D 187, mesuagenin E 188, mesuagenin A 189, mesuagenin B 190 and mesuagenin C 191, of which one is new; mesuagenin E 188. Bioassay-guided study of the bark from M. elegans afforded mesuagenin B 190 from the hexane fraction as the active constituent for acetylcholinesterase (AChE) inhibition activity with an IC50 value of 0.70 μM. Further isolation work carried out on this hexane extract afforded more natural 4-phenylcoumarins Semi-synthetic work was done on the major 4-phenylcoumarins from this extract, which afforded seventeen semi-synthetic compounds. All of the natural and semi-synthetic 4-phenylcoumarin analogues were subjected to a SAR study for AChE activity. Another bioassay-guided study was carried out to isolate and evaluate the neuroprotective compounds from the hexane extract of the bark of M. kunstleri. Mesuagenin C 191 was isolated as the most active compound; cell viability data demonstrated that this compound significantly increased cell viability (78.99 ± 3.49%) after NG108-15 cells were exposed to 2 mM H2O2 and 2 hours of pretreatment with mesuagenin C 191.

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