title: Comparative in vivo evaluation of polyalkoxy substituted 4H-chromenes and oxa-podophyllotoxins as microtubule destabilizing agents in the phenotypic sea urchin embryo assay.
abstract: A series of polyalkoxy substituted 7-hydroxy- and 7-methoxy-4-aryl-4H-chromenes were evaluated using the sea urchin embryo model to yield several compounds exhibiting potent antimitotic microtubule destabilizing activity. Data obtained by the assay were further confirmed in the NCI60 human cancer cell screen. The replacement of methylenedioxy ring A and lactone ring D in podophyllotoxin analogues by 7-methoxy, 2-NH2, and 3-CN groups in 4-aryl-4H-chromenes resulted in potent antimitotic microtubule destabilizing agents. Feasible synthesis and high yields render 7-methoxy-4H-chromenes to be a promising series for further anticancer drug development.
authors.affiliation: Institute of Developmental Biology, RAS, Vavilov Street, 26, 119334 Moscow, Russia; Chemical Block Ltd, 3 Kyriacou Matsi, 3723 Limassol, Cyprus. Electronic address: ms@chemical-block.com.
authors.forename: Marina N
authors.initials: MN
authors.lastname: Semenova
authors.affiliation: N. D. Zelinsky Institute of Organic Chemistry, RAS, Leninsky Prospect, 47, 119991 Moscow, Russia. Electronic address: tsyg@ioc.ac.ru.
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Tsyganov
authors.affiliation: N. D. Zelinsky Institute of Organic Chemistry, RAS, Leninsky Prospect, 47, 119991 Moscow, Russia. Electronic address: olegmalyshev1969@gmail.com.
authors.forename: Oleg R
authors.initials: OR
authors.lastname: Malyshev
authors.affiliation: I. N. Ulyanov Chuvash State University, Moskovskiy pr., 15, 428015 Cheboksary, Russia. Electronic address: oleg.ershov@mail.ru.
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Ershov
authors.affiliation: I. N. Ulyanov Chuvash State University, Moskovskiy pr., 15, 428015 Cheboksary, Russia. Electronic address: bardasov.chem@mail.ru.
authors.forename: Ivan N
authors.initials: IN
authors.lastname: Bardasov
authors.affiliation: N. D. Zelinsky Institute of Organic Chemistry, RAS, Leninsky Prospect, 47, 119991 Moscow, Russia. Electronic address: rs@chemical-block.com.
authors.forename: Roman V
authors.initials: RV
authors.lastname: Semenov
authors.affiliation: Department of Biological and Medicinal Chemistry, Moscow Institute of Physics and Technology, Institutsky Per. 9, Dolgoprudny, Moscow Region 141700, Russia. Electronic address: ask@chemdiv.com.
authors.forename: Alex S
authors.initials: AS
authors.lastname: Kiselyov
authors.affiliation: Chemical Block Ltd, 3 Kyriacou Matsi, 3723 Limassol, Cyprus; N. D. Zelinsky Institute of Organic Chemistry, RAS, Leninsky Prospect, 47, 119991 Moscow, Russia. Electronic address: vs@zelinsky.ru.
authors.forename: Victor V
authors.initials: VV
authors.lastname: Semenov
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D010641:Phenotype; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D012617:Sea Urchins / Q000166:cytology / Q000187:drug effects* / Q000196:embryology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D011034:Podophyllotoxin
keywords: 4H-Chromenes; Cytotoxicity; Microtubule destabilizing agents; Oxa-podophyllotoxins; Sea urchin embryo