ABSTRACT
Certain coumarin alpha-methylene-gamma-butyrolactones were synthesized and evaluated for antiproliferative and vasorelaxing activities. These compounds were synthesized via alkylation of hydroxycoumarins 2a-f followed by oxidation and the Reformatsky-type condensation. The results of this study are as follows (1) for the vasorelaxing activity, coumarin-7-yl alpha-methylene-gamma-butyrolactone 6d, with an IC50 value of 9.4 microM against pig coronary arterial contraction induced by KCl, is a more active vasorelaxant than its coumarin-4-yl counterpart 6a and its gamma-methyl congener 1. A methyl group substituted at C-4 of the coumarin-7-yl moiety reduced the vasorelaxing effect (6d vs 6e) while the 3,4,8-trimethyl derivative 6f was inactive. (2) For the antiproliferative activity, coumarin-4-yl alpha-methylene-gamma-butyrolactone 6a, which exhibited the most potent antiproliferative activity on the growth of MCF7, NCI-H460, and SF-268 with IC50 values of 6.97, 14.68, and 8.36 microM, respectively, is more cytotoxic than its coumarin-7-yl counterpart 6d and the 6,7-dimethyl derivative 6b. For the coumarin-7-yl derivatives, 6d is more active than its gamma-methyl congener 1, indicating that substitution at the gamma-position decreased cytotoxicity.
Subject(s)
4-Butyrolactone/chemical synthesis , 4-Butyrolactone/pharmacology , Cell Division/drug effects , Vasodilation/drug effects , 4-Butyrolactone/chemistry , Animals , Coronary Vessels/drug effects , Drug Evaluation, Preclinical , In Vitro Techniques , Magnetic Resonance Spectroscopy , SwineABSTRACT
A steryl epoxide, machillene (1), a secobutanolide, secomahubanolide (2), and two butanolides, zuihoenalide (3), and 3-(1-methoxyoctadecyl)-5-methylene-5H-furan-2-one (4), together with 12 known compounds, were isolated from stem wood of Machilus zuihoensis. Their structures were determined by means of spectroscopic analyses. Machillene (1) showed cytotoxic activity against NUGC-3 and HONE-1 cancer cell lines in vitro.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Epoxy Compounds/chemistry , Furans/chemistry , Lauraceae/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Butanes/chemistry , Cell Line, Tumor , Humans , Molecular Structure , WoodABSTRACT
Three polyketide compounds, surinone A, surinone B, surinone C and one acylresorcinol, suranone, along with thirty known compounds, were isolated from the whole plant of Peperomia sui. Their structures were elucidated from spectral analysis. Several compounds showed cytotoxic activity against HONE-1 and NUGC-3 cell lines in vitro.
