title: Heteroaromatic analogs of the resveratrol analog DMU-212 as potent anti-cancer agents.
abstract: Heteroaromatic analogs of DMU-212 (8-15) have been synthesized and evaluated for their anti-cancer activity against a panel of 60 human cancer cell lines. These novel analogs contain a trans-3,4,5-trimethoxystyryl moiety attached to the C2 position of indole, benzofuran, benzothiazole or benzothiophene ring (8, 11, 13 and 14, respectively) and showed potent growth inhibition in 85% of the cancer cell lines examined, with GI50 values <1 μM. Interestingly, trans-3,4- and trans-3,5-dimethoxystyryl DMU-212 analogs 9, 10, 12 and 15 exhibited significantly less growth inhibition than their 3,4,5-trimethoxystyryl counterparts, suggesting that the trans-3,4,5-trimethoxystyryl moiety is an essential structural element for the potent anti-cancer activity of these heterocyclic DMU-212 analogs. Molecular modeling studies showed that the four most active compounds (8, 11, 13 and 14) all bind to the colchicine binding site on tubulin, and that their binding modes are similar to that of DMU-212.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors.forename: Narsimha Reddy
authors.initials: NR
authors.lastname: Penthala
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors.forename: Shraddha
authors.initials: S
authors.lastname: Thakkar
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States. Electronic address: pacrooks@uams.edu.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Crooks
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001572:Benzofurans / Q000737:chemistry; D052160:Benzothiazoles / Q000737:chemistry; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D003078:Colchicine / Q000737:chemistry / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D000077185:Resveratrol; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013876:Thiophenes / Q000737:chemistry; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
chemical_list: C482492:3,4,5,4'-tetramethoxystilbene; D000970:Antineoplastic Agents; D001572:Benzofurans; D052160:Benzothiazoles; D013267:Stilbenes; D013876:Thiophenes; D014404:Tubulin; C088015:benzothiophene; C005465:benzothiazole; C105430:benzofuran; D000077185:Resveratrol; D003078:Colchicine
keywords: Anti-cancer activity; Benzofuran; Benzothiazole; Benzothiophene; Heterocyclic resveratrol analogs; Indole