Chemical constituents and biological activities from Miliusa sessilis Chaowasku & Kessler

Abstract

Bioassay-guided fractionation of the hexane and ethyl acetate extracts of the leaves of Miliusa sessilis Chaowasku & Kessler sp. nov. (Annoaceae) led to the isolation of nine new neolignans including four dihydro[b]benzofuran neolignans: (7S,8R)-5'-hydroxy-3,4-dimethoxy-4',7-epoxy-8,3'-neolign-8'-en-9-acetate (MS12), (7S,8R)-3,4,5'-trimethoxy-4',7-epoxy-8,3'-neolign-8'-en-9-ol (MS15), (7S,8R)-5'-hydroxy-3,4-dimethoxy-4',7-epoxy-8,3'-neolign-8'-en-9-ol (MS17) and (7R,8S)-3,4,5'-trimethoxy-4',7-epoxy-8,3'-neolign-8'-en-9-acetate (MS11), three 8-O-4′ neolignans: threo-(7R,8R)-3,3',4-trimethoxy-8,4'-oxyneolign-8'-en-7-ol-9-acetate (MS16), threo-(7R,8R)-3,3',4-trimethoxy-8,4'-oxyneolign-8'-en-7,9-diol (MS19) and threo-3,4-dihydroxy-3',5-dimethoxy-8,4'-oxyneolign-8'-en-7,9-diol (MS20), one dineolignan: (7R,8R)-4'-hydroxy-3,4,5'-trimethoxy-8,3'-neolign-8'-en-7,9-diol (MS14) and one phenylpropanoid dimer: 4-hydroxy-3',5-dimethoxy-3,4'-oxyneolign-7',8-dien-9'-ol (MS18), and four new triterpenes: (3β,23S)-23-methoxy-24-methylenelanost-9-en-3-ol (MS3), (3β,23S)-23-methoxy-24-methylenenorlanost-9-en-3-ol (MS5), (3β)-24,241-epoxy-lanost-9-en-3-ol (MS6) and (3β,16β)-24-methylenelanost-9-en-3,16-diol (MS7), together with seven other known compounds, including, two neolignans: dehydrodieugenol A (MS10) and dehydrodieugenol B (MS13), two sesquiterpenes: (+)-spathulenol (MS1) and T-muurolol (MS4), phytol (MS2) and a mixture of stigmasterol (MS8) and β-sitosterol (MS9). Their structures were elucidated by extensive spectroscopic analysis. The structures of MS12, MS3, MS5 and MS7 were further confirmed by X-ray crystallographic analysis. The absolute configurations were determined using circular dichroism (CD) data analysis and the modified Mosher’s method. All isolated compounds were also evaluated for their cytotoxic activities against four human cancer cell lines (HeLa, HN22, HepG2 and HCT116), including one normal-type cell line (HaCaT) using MTT assay. MS17 was found to exhibit the most promising cytotoxic effect against Hela cells with the lowest IC50 value of 0.04 mM and the highest selective index of 187.8.

Bioassay-guided fractionation of the hexane and ethyl acetate extracts of the leaves of Miliusa sessilis Chaowasku & Kessler sp. nov. (Annoaceae) led to the isolation of nine new neolignans including four dihydro[b]benzofuran neolignans: (7S,8R)-5'-hydroxy-3,4-dimethoxy-4',7-epoxy-8,3'-neolign-8'-en-9-acetate (MS12), (7S,8R)-3,4,5'-trimethoxy-4',7-epoxy-8,3'-neolign-8'-en-9-ol (MS15), (7S,8R)-5'-hydroxy-3,4-dimethoxy-4',7-epoxy-8,3'-neolign-8'-en-9-ol (MS17) and (7R,8S)-3,4,5'-trimethoxy-4',7-epoxy-8,3'-neolign-8'-en-9-acetate (MS11), three 8-O-4′ neolignans: threo-(7R,8R)-3,3',4-trimethoxy-8,4'-oxyneolign-8'-en-7-ol-9-acetate (MS16), threo-(7R,8R)-3,3',4-trimethoxy-8,4'-oxyneolign-8'-en-7,9-diol (MS19) and threo-3,4-dihydroxy-3',5-dimethoxy-8,4'-oxyneolign-8'-en-7,9-diol (MS20), one dineolignan: (7R,8R)-4'-hydroxy-3,4,5'-trimethoxy-8,3'-neolign-8'-en-7,9-diol (MS14) and one phenylpropanoid dimer: 4-hydroxy-3',5-dimethoxy-3,4'-oxyneolign-7',8-dien-9'-ol (MS18), and four new triterpenes: (3β,23S)-23-methoxy-24-methylenelanost-9-en-3-ol (MS3), (3β,23S)-23-methoxy-24-methylenenorlanost-9-en-3-ol (MS5), (3β)-24,241-epoxy- lanost-9-en-3-ol (MS6) and (3β,16β)-24-methylenelanost-9-en-3,16-diol (MS7), together with seven other known compounds, including, two neolignans: dehydrodieugenol A (MS10) and dehydrodieugenol B (MS13), two sesquiterpenes: (+)-spathulenol (MS1) and T-muurolol (MS4), phytol (MS2) and a mixture of stigmasterol (MS8) and β-sitosterol (MS9). Their structures were elucidated by extensive spectroscopic analysis. The structures of MS12, MS3, MS5 and MS7 were further confirmed by X-ray crystallographic analysis. The absolute configurations were determined using circular dichroism (CD) data analysis and the modified Mosher’s method. All isolated compounds were also evaluated for their cytotoxic activities against four human cancer cell lines (HeLa, HN22, HepG2 and HCT116), including one normal-type cell line (HaCaT) using MTT assay. MS17 was found to exhibit the most promising cytotoxic effect against Hela cells with the lowest IC50 value of 0.04 mM and the highest selective index of 187.8.