title: The structure-activity relationship between synthetic butylidenephthalide derivatives regarding the competence and progression of inhibition in primary cultures proliferation of mouse aorta smooth muscle cells.
abstract: The inhibitory effects of synthetic butylidenephthalide (BP) derivatives on 10% fetal bovine serum-stimulated proliferation were assayed by measuring the proliferative cell number at an interval of 12 h in primary cultures of mouse aorta smooth muscle cells (SMC). Their potencies for the anti-proliferation effect were in the order BP-42 (4,5-dihydroxy BP) > BP-92 (4,5-dihydroxy butylphthalide) > BP-97 (6,7-dihydroxy-3-(3-bromo-1-octenyl)-phthalide) > BP-82 (6,7-dihydroxy BP) > BP-86 (5,6-dihydroxy BP) > BP-87 (4,5,6-trihydroxy BP) > BP-85 (4,7-dihydroxy BP) > BP-84 (5,7-dihydroxy BP) > BP-4C3 (4-methoxy propylphthalide) > BP-7 (4-hydroxy BP) > BP-40 (4,5-dimethoxy butylphthalide) > BP-5C3 (4-hydroxy propylphthalide). We divided these anti-proliferative effects into anti-competence and anti-progression effects by using a convenient assay. BP-42 had the greatest potency in used phthalides for competence inhibition of the SMC proliferation. BP-92 had small potency for competence inhibition. BP-97 had greater potency for competence inhibition than BP-82. These results demonstrated that the anti-proliferative effect of BP-42 was greatest in used phthalides in primary cultures of vascular SMC. The 4,5-dihydroxy group and 3-butylidene or 3-(3-bromo-1-octenyl) group in these synthetic BP derivatives contributed to the anti-competence effect on SMC. BP-42 may become a prototype of an anti-atherosclerotic drug.
authors.affiliation: Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Mimura
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Naitoh
authors.forename: I
authors.initials: I
authors.lastname: Kimura
authors.forename: M
authors.initials: M
authors.lastname: Kimura
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001161:Arteriosclerosis / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010796:Phthalic Anhydrides / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D010796:Phthalic Anhydrides; C026105:butylidenephthalide