10-Alkoxy-anthracenyl-isoxazole analogs have sub-micromolar activity against a Glioblastoma multiforme cell line

Bioorg Med Chem. 2022 Sep 1:69:116911. doi: 10.1016/j.bmc.2022.116911. Epub 2022 Jul 1.

Abstract

A series of 10-alkoxy-Anthryl-isoxazole-pyrrole-doubletails (RO-AIMs) were synthesized using a crown ether assisted nucleophilic aromatic substitution followed by a modified Schotten-Baumann reaction. The novel RO-AIMs described here exhibit robust growth inhibition for the human SNB19 CNS glioblastoma cell line, and biphenyl analog 8c had activity in the nanomolar regime, which represents the most efficacious compound in the AIM series to date. Computational modeling for RO-AIMs binding in a ternary complex with c-myc quadruplex DNA and its helicase DHX36 is presented which represents our current working hypothesis.

Keywords: Anti-tumor; Isoxazole; Pyrrole; Quadruplex DNA; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alcohols
  • Cell Line
  • Cell Line, Tumor
  • G-Quadruplexes*
  • Glioblastoma* / drug therapy
  • Humans
  • Isoxazoles

Substances

  • Alcohols
  • Isoxazoles
  • alkoxyl radical