title: Polyalkoxy substituted 4H-chromenes: synthesis by domino reaction and anticancer activity.
abstract: A series of 4H-chromenes containing various modifications in the ring B and polyalkoxy substituents in the ring E has been synthesized by Knoevenagel-Michael-hetero-Thorpe-Ziegler three-component domino reaction with the overall yield of 45-82%. The targeted molecules were evaluated in a phenotypic sea urchin embryo assay for antimitotic and microtubule destabilizing activity. The most active compounds 5{1,5} and 5{5,5} featured sesamol-derived ring B and m-methoxyphenyl or m-methoxymethylenedioxyphenyl ring E. Compounds 5{3,1}, 5{1,2}, 5{5,4}, 5{1,5}, and 5{5,5} exhibited strong cytotoxicity in the NCI60 human tumor cell line anticancer drug screen. Surprisingly, cell growth inhibition caused by these agents was more pronounced in the multidrug resistant NCI/ADR-RES cells than the parent OVCAR-8 cell line. The results suggest that polyalkoxy substited 4H-chromenes may prove to be advantageous for further design as anticancer agents.
authors: N. D. Zelinsky Institute of Organic Chemistry, RAS, Moscow, Russian Federation. amsh@ioc.ac.ru
authors: Anatoliy M
authors: AM
authors: Shestopalov
authors: Yuri M
authors: YM
authors: Litvinov
authors: Lyudmila A
authors: LA
authors: Rodinovskaya
authors: Oleg R
authors: OR
authors: Malyshev
authors: Marina N
authors: MN
authors: Semenova
authors: Victor V
authors: VV
authors: Semenov
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012617:Sea Urchins / Q000166:cytology / Q000187:drug effects* / Q000196:embryology
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D011108:Polymers