In-silico design and synthesis of N9-substituted β-Carbolines as PLK-1 inhibitors and their in-vitro/in-vivo tumor suppressing evaluation

Gomathi Priya Jeyapal, Rajendiran Krishnasamy, Carolyn K. Suzuki, Sundararajan Venkatesh, M. J.N. Chandrasekar

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

A new series of β-Carboline/Schiff bases was designed, synthesized, characterised and biologically evaluated as inhibitors of PLK-1. The synthesized compounds exhibited strong to moderate cytotoxic activities against NCI-60 panel cell assay. Compound SB-2 was the most potent, particularly against colon with GI 50 of 3–45 µM on NCI-60 panel cell lines. SB-2 selectively inhibited PLK-1 at 15 µM on KinomeScan screening. It also showed a dose-dependent cell cycle arrest at S/G2 phase on HCT-116 and induced apoptosis by the activation of procaspase-3 and cleaved PARP. Further, the antitumor studies on DLA and EAC model revealed that SB-2, at 100 mg/kg/bd.wt significantly increased their average lifespan. Further, a decrease in the body weight of the tumor-bearing mice was also observed when compared to the tumor controlled mice. SB-2 thus shows good potential as antitumor agent.

Original languageEnglish (US)
Article number102913
JournalBioorganic Chemistry
Volume88
DOIs
StatePublished - Jul 2019

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

Keywords

  • Anticancer
  • Apoptosis
  • Cell cycle
  • Cytotoxicity
  • PLK-1
  • β-Carboline

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