title: Synthesis and cytostatic properties of polyfunctionalized furanoallocolchicinoids.
abstract: A series of furan-based allocolchicinoids was prepared from commercially available colchicine via a nine-step reaction sequence. Cytostatic activity, cell cycle arrest, apoptosis, tubulin and F-actin expression were studied in vitro in 2D and 3D cultures of normal and tumor epithelial keratinocytes, endothelial and mesenchymal cells. Among the prepared furanoallocolchicine analogues, 14a and 7a displayed the most pronounced anti-cancer activity. These compounds induced two types of effects: (a) cell cycle arrest in the G2/M phase as a direct consequence of effective tubulin binding (metaphase effect), and (b) pronounced cell stress (as evidenced by the overexpression of tubulin and F-actin), which was caused by the hyperpolarization of mitochondrial and lysosomal membranes (interphase effect).
authors.affiliation: Department of Organic Chemistry, Nizhni Novgorod State University, Gagarina av. 23, Nizhni Novgorod, 603950, Russian Federation.
authors.forename: Iuliia A
authors.initials: IA
authors.lastname: Gracheva
authors.affiliation: Department of Organic Chemistry, Nizhni Novgorod State University, Gagarina av. 23, Nizhni Novgorod, 603950, Russian Federation.
authors.forename: Iuliia V
authors.initials: IV
authors.lastname: Voitovich
authors.affiliation: Department of Organic Chemistry, Nizhni Novgorod State University, Gagarina av. 23, Nizhni Novgorod, 603950, Russian Federation.
authors.forename: Vladimir I
authors.initials: VI
authors.lastname: Faerman
authors.affiliation: Department of Organic Chemistry, Nizhni Novgorod State University, Gagarina av. 23, Nizhni Novgorod, 603950, Russian Federation.
authors.forename: Nikolay S
authors.initials: NS
authors.lastname: Sitnikov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russian Federation.
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Myrsikova
authors.affiliation: Department of Chemistry, University of Cologne, Greinstrasse 4, 50939 Köln, Germany. Electronic address: schmalz@uni-koeln.de.
authors.forename: Hans-Gunther
authors.initials: HG
authors.lastname: Schmalz
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russian Federation; Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation, Moscow, Russian Federation. Electronic address: esvir@yandex.ru.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Svirshevskaya
authors.affiliation: Department of Organic Chemistry, Nizhni Novgorod State University, Gagarina av. 23, Nizhni Novgorod, 603950, Russian Federation. Electronic address: afnn@rambler.ru.
authors.forename: Alexey Yu
authors.initials: AY
authors.lastname: Fedorov
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D003078:Colchicine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D054697:Cytostatic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D005663:Furans / Q000737:chemistry*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism
chemical_list: D054697:Cytostatic Agents; D005663:Furans; D014404:Tubulin; D003078:Colchicine
keywords: Allocolchicinoids; Antitumor activity; Colchicine; Cross-coupling; Tubulin binding agents