Discovery of 5-sulfonyltetrazoles as neuroblastoma differentiation agents

Bioorg Med Chem Lett. 2023 Oct 1:94:129455. doi: 10.1016/j.bmcl.2023.129455. Epub 2023 Aug 18.

Abstract

Previously, we developed an innovative high-content screening (HCS) approach to quantify neuroblastoma cell differentiation based on neurite outgrowth, a morphological differentiation marker of neuroblastoma cells. Here, we report the utilization of this platform to identify 1-methyl-5-(ethylsulfonyl)-1H-tetrazole (3a) as a new neuroblastoma differentiation agent using the ChemBridge DiversetTM commercial synthetic small molecule compound library. We show that this activity can be extended to a group of analogues, which can be accessed via a short two-step synthetic sequence. A new analogue, 5-(allylsulfonyl)-1-methyl-1H-tetrazole (3c) was identified in this synthetic effort as a compound that has even more pronounced differentiation and cytotoxic activities than the original hit compound 3a.

Keywords: Differentiation; Heterocycle; High throughput screening; Library; Neuroblastoma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Cell Differentiation
  • Gene Library
  • Humans
  • Neuroblastoma* / drug therapy
  • Neuronal Outgrowth

Substances

  • Antineoplastic Agents