E. V. Nurieva, N. A. Zefirov, N. Fritsch, E. R. Milaeva, S. A. Kuznetsov, O. N. Zefirova, “Molecular design and synthesis of new heterobivalent compounds based on chlorambucil and colchicine”, Mendeleev Commun., 2020, Volume 30, Issue 6,Pages <nobr>706

This article is cited in 4 papers

Communications

Molecular design and synthesis of new heterobivalent compounds based on chlorambucil and colchicine

E. V. Nurieva^a, N. A. Zefirov^ab, N. Fritsch^c, 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: Two new heterobivalent molecules were designed by linking a DNA-alkylating agent chlorambucil with tubulin-targeting compound colchicine or its adamantyl containing C(7)-derivative. Target compounds were synthesized via acid coupling with N-deacetylcolchicine. According to preliminary biotests, both conjugates caused microtubule depolymerization and strong tubulin clustering, and colchicine–chlorambucil conjugate was found to be one order of magnitude more potent and to exhibit some selectivity to A549 carcinoma cells.

Keywords: heterobivalent compounds, dual target profile, twin drugs, chlorambucil, colchicine, adamantane, tubulin, lung carcinoma A549.

Language: English

DOI: 10.1016/j.mencom.2020.11.005

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