2. Academic Validation
  3. Synthesis, modeling, and biological evaluation of anti-tubulin indole-substituted furanones

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

  • Bioorg Med Chem Lett. 2023 Jun 15;90:129347. doi: 10.1016/j.bmcl.2023.129347.
Brianna Hurysz 1,  Blake A Evans 2,  Reuben N Laryea 3,  Brooke E Boyer 2,  Taylor E Coburn 2,  Molly S Dexter 4,  Marissa A Edwards 2,  Grace V Faulkner 2,  Rebecca L Huss 2,  Megan M Lafferty 2,  Maegan Manning 1,  Matthew McNulty 1,  Sophia J Melvin 2,  Christina M Mitrow 2,  Roslyn R Patel 2,  Kelsey Pierce 1,  Jack Russo 2,  Allie M Seminer 2,  Kaitlynn A Sockett 2,  Nathan R Webster 2,  Kathryn E Cole 5,  Patricia Mowery 6,  Erin T Pelkey 7
Affiliations

Affiliations

  • 1 Department of Biology, Hobart and William Smith Colleges, Geneva, NY 14456, USA.
  • 2 Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA.
  • 3 Department of Molecular Biology and Chemistry, Christopher Newport University, Newport News, VA 23606, USA.
  • 4 Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA; Department of Biology, Hobart and William Smith Colleges, Geneva, NY 14456, USA.
  • 5 Department of Molecular Biology and Chemistry, Christopher Newport University, Newport News, VA 23606, USA. Electronic address: [email protected].
  • 6 Department of Biology, Hobart and William Smith Colleges, Geneva, NY 14456, USA. Electronic address: [email protected].
  • 7 Department of Chemistry, Hobart and William Smith Colleges, Geneva, NY 14456, USA. Electronic address: [email protected].
PMID: 37236376 DOI: 10.1016/j.bmcl.2023.129347
Abstract

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.

Keywords

Antiproliferative; Antitubulin; Heterocyclic; Indole.

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