N. A. Zefirov, Yu. A. Evteeva, A. I. Krasnoperova, A. V. Mamaeva, E. R. Milaeva, S. A. Kuznetsov, O. N. Zefirova, “Tubulin targeted antimitotic agents based on adamantane lead compound: synthesis, SAR and molecular modeling”, Mendeleev Commun., 2020, Volume 30, Issue 4,Pages <nobr>421

This article is cited in 12 papers

Communications

Tubulin targeted antimitotic agents based on adamantane lead compound: synthesis, SAR and molecular modeling

N. A. Zefirov^ab, Yu. A. Evteeva^a, A. I. Krasnoperova^a, A. V. Mamaeva^a, E. R. Milaeva^ab, S. A. Kuznetsov^c, O. N. Zefirova^ab

^a Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow, Russian Federation
^b Institute of Physiologically Active Compounds, Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Chernogolovka, Moscow Region, Russian Federation
^c Institute of Biological Sciences, Cell Biology and Biosystems Technology, University of Rostock, Rostock, Germany

Abstract: 5-Hydroxymethyl-2-methoxyphenyl adamantane-1-acetate inhibits cell proliferation and stimulates depolymerization of microtubules of cancer cells to free tubulin. Its analogues were synthesized via the Steglich or Mitsunobu reactions to determine the role of structural subunits of the molecule in tubulin binding. Based on the structure–activity relationship studies, metabolically stable 1-[2-(5-hydroxymethyl-2-methoxyphenyl)ethyl]adamantane was invented, which exhibits a dual-target profile and retains in vitro activity observed for the lead compound.

Keywords: adamantane, tubulin, colchicine binding site, lung carcinoma A549, dual-target profile, structure–activity relationship.

Language: English

DOI: 10.1016/j.mencom.2020.07.005

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