Methyl 3-((6-methoxy-1,4-dihydroindeno[1,2-c]pyrazol-3-yl)amino)benzoate (GN39482) as a tubulin polymerization inhibitor identified by morphobase and chemproteobase profiling methods

Hidemitsu Minegishi, Yushi Futamura, Shinji Fukashiro, Makoto Muroi, Makoto Kawatani, Hiroyuki Osada, Hiroyuki Nakamura*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

A series of indenopyrazoles was synthesized from the corresponding indanones and phenyl isothiocyanates in two steps. Among the compounds synthesized, methyl 3-((6-methoxy-1,4-dihydroindeno[1,2-c]pyrazol-3-yl)amino)benzoate 6m (GN39482) was found to possess a promising antiproliferative activity toward human cancer cells without affecting any antimicrobial and antimalarial activities at 100 nM. Both a methoxy group at R1 position and a methoxycarbonyl group at R2 position of the anilinoquinazoline framework are essential for the high cell growth inhibition. Both MorphoBase and ChemProteoBase profiling analyses suggested that compound 6m was classified as a tubulin inhibitor. Indeed, compound 6m inhibited the acetylated tubulin accumulation and the microtubule formation and induced G2/M cell cycle arrest in HeLa cells, revealing that a promising antiproliferative activity of compound 6m toward human cancer cells is probably caused by the tubulin polymerization inhibition.

Original languageEnglish
Pages (from-to)4230-4241
Number of pages12
JournalJournal of Medicinal Chemistry
Volume58
Issue number10
DOIs
Publication statusPublished - 2015 May 28
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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