Synthesis and evaluation of a series of benzothiophene acrylonitrile analogs as anticancer agents

Narsimha Reddy Penthala, Vijayakumar N. Sonar, Jamie Horn, Markos Leggas, Jai Shankar K.B. Yadlapalli, Peter A. Crooks

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


A new library of small molecules with structural features resembling combretastatin analogs was synthesized and evaluated for anticancer activity against a panel of 60 human cancer cell lines. Three novel acrylonitrile analogs (5, 6 and 13) caused a significant reduction in cell growth in almost all the cell lines examined, with GI50 values generally in the range 10-100 nM. Based on the structural characteristics of similar drugs, we hypothesized that the cytotoxic activity was likely due to interaction with tubulin. Furthermore, these compounds appeared to overcome cell-associated P-glycoprotein (P-gp)-mediated resistance, since they were equipotent in inhibiting OVCAR8 and NCI/ADR-RES cell growth. Given that antitubulin drugs are among the most effective agents for the treatment of advanced prostate cancer we sought to validate the results from the 60 cell panel by studying the representative analog 6 utilizing prostate cancer cell lines, as well as exploring the molecular mechanism of the cytotoxic action of this analog.

Original languageEnglish
Pages (from-to)1073-1078
Number of pages6
Issue number7
StatePublished - Jul 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry


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