2. Academic Validation
  3. Synthesis and cytostatic properties of polyfunctionalized furanoallocolchicinoids

Synthesis and cytostatic properties of polyfunctionalized furanoallocolchicinoids

  • Eur J Med Chem. 2017 Jan 27:126:432-443. doi: 10.1016/j.ejmech.2016.11.020.
Iuliia A Gracheva 1,  Iuliia V Voitovich 1,  Vladimir I Faerman 1,  Nikolay S Sitnikov 1,  Ekaterina V Myrsikova 2,  Hans-Gunther Schmalz 3,  Elena V Svirshevskaya 4,  Alexey Yu Fedorov 5
Affiliations

Affiliations

  • 1 Department of Organic Chemistry, Nizhni Novgorod State University, Gagarina av. 23, Nizhni Novgorod, 603950, Russian Federation.
  • 2 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russian Federation.
  • 3 Department of Chemistry, University of Cologne, Greinstrasse 4, 50939 Köln, Germany. Electronic address: schmalz@uni-koeln.de.
  • 4 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.
  • 5 Department of Organic Chemistry, Nizhni Novgorod State University, Gagarina av. 23, Nizhni Novgorod, 603950, Russian Federation. Electronic address: afnn@rambler.ru.
PMID: 27912174 DOI: 10.1016/j.ejmech.2016.11.020
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).

Keywords

Allocolchicinoids; Antitumor activity; Colchicine; Cross-coupling; Tubulin binding agents.

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