Synthesis, modeling, and biological evaluation of anti-tubulin indole-substituted furanones.

Autor: Hurysz B; Department of Biology, Hobart and William Smith Colleges, Geneva, NY 14456, USA., Evans BA; Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA., Laryea RN; Department of Molecular Biology and Chemistry, Christopher Newport University, Newport News, VA 23606, USA., Boyer BE; Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA., Coburn TE; Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA., Dexter MS; Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA; Department of Biology, Hobart and William Smith Colleges, Geneva, NY 14456, USA., Edwards MA; Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA., Faulkner GV; Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA., Huss RL; Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA., Lafferty MM; Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA., Manning M; Department of Biology, Hobart and William Smith Colleges, Geneva, NY 14456, USA., McNulty M; Department of Biology, Hobart and William Smith Colleges, Geneva, NY 14456, USA., Melvin SJ; Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA., Mitrow CM; Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA., Patel RR; Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA., Pierce K; Department of Biology, Hobart and William Smith Colleges, Geneva, NY 14456, USA., Russo J; Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA., Seminer AM; Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA., Sockett KA; Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA., Webster NR; Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA., Cole KE; Department of Molecular Biology and Chemistry, Christopher Newport University, Newport News, VA 23606, USA. Electronic address: kathryn.cole@cnu.edu., Mowery P; Department of Biology, Hobart and William Smith Colleges, Geneva, NY 14456, USA. Electronic address: mowery@hws.edu., Pelkey ET; Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA. Electronic address: pelkey@hws.edu.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2023 Jun 15; Vol. 90, pp. 129347. Date of Electronic Publication: 2023 May 24.
DOI: 10.1016/j.bmcl.2023.129347
Abstrakt: Due to the central role of tubulin in various cellular functions, it is a validated target for anti-cancer therapeutics. However, many of the current tubulin inhibitors are derived from complex natural products and suffer from multidrug resistance, low solubility, toxicity issues, and/or the lack of multi-cancer efficacy. As such, there is a continued need for the discovery and development of new anti-tubulin drugs to enter the pipeline. Herein we report on a group of indole-substituted furanones that were prepared and tested for anti-cancer activity. Molecular docking studies showed positive correlations between favorable binding in the colchicine binding site (CBS) of tubulin and anti-proliferative activity, and the most potent compound was found to inhibit tubulin polymerization. These compounds represent a promising new structural motif in the search for small heterocyclic CBS cancer inhibitors.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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