[3+2]-Annulation of pyridinium ylides with 1-chloro-2-nitrostyrenes unveils a tubulin polymerization inhibitor

• Authors: Alexander V Aksenov, North Caucasus Federal University; Nikolai A Arutiunov, North Caucasus Federal University; Nikita K Kirilov, North Caucasus Federal University; Dmitrii A Aksenov, North Caucasus Federal University; Igor Y Grishin, North Caucasus Federal University; NicolaiA Aksenov, North Caucasus Federal University; Huifen Wang, Texas State University; Liqin Du, Texas State University; Tania Betancourt, Texas State University; Stephen C Pelly, Emory University; Alexander Kornienko, Texas State University; Michael Rubin, North Caucasus Federal University
• Journal Title: ORGANIC & BIOMOLECULAR CHEMISTRY
• Volume: Volume 19, Number 33
• Publisher: ROYAL SOC CHEMISTRY | 2021-08-05, Pages 7234-7245
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1039/d1ob01141c
• Subjects: Chemistry, General
• Keywords: Science & Technology; Physical Sciences; Chemistry, Organic; Chemistry; LAMELLARIN ALKALOIDS; EFFICIENT SYNTHESIS; ANTICANCER; DERIVATIVES; INDOLIZINES; CAMPTOTHECIN; NITROALKANES; HETEROCYCLES; RESISTANCE; DISCOVERY

Abstract

Indolizines and pyrazolo[1,5-a]pyridines were prepared via [3 + 2]-cycloaddition of pyridinium ylides to 1-chloro-2-nitrostyrenes. The synthesized molecules were evaluated for antiproliferative activities against a BE(2)-C neuroblastoma cell line with several compounds decreasing the viability of cancer cells. Indolizine 9db showed higher potency than that of all-trans-retinoic acid, an approved cancer drug. Mechanistically, it was found to inhibit tubulin polymerization and it is thus proposed that the discovered chemistry can be exploited for the development of novel microtubule-targeting anticancer agents.