Synthesis of novel potential ROCK inhibitors and their antimigratory effects


Turanli S., Uslu A. G. , ÖZDEMİR A.

ORGANIC COMMUNICATIONS, vol.13, no.4, pp.165-174, 2020 (Journal Indexed in ESCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 13 Issue: 4
  • Publication Date: 2020
  • Doi Number: 10.25135/acg.oc.87.20.10.1846
  • Title of Journal : ORGANIC COMMUNICATIONS
  • Page Numbers: pp.165-174
  • Keywords: ROCK, migration, MCF-7, benzoxazolone, benzimidazole, urea, RHO-KINASE INHIBITORS, DESIGN, DISCOVERY, INVASION, OPTIMIZATION, DERIVATIVES, PATHWAY, PROTEIN

Abstract

Rho kinase (ROCK), an enzyme belonging to the serine-threonine kinase family, is involved in the regulation of basic cellular processes such as morphology, movement, division, differentiation and apoptosis. On the other hand, excessively activated ROCK can cause to cardiovascular and neurological disorders or cancer. In recent years, overactivation of Rho kinases has been associated with increased metastasis in various tumor types and has been explored as target for the development of new anticancer drugs. We report here the design and synthesis of five urea derivatives in search of novel inhibitors of cancer cell migration. Compounds evaluated for their cytotoxic activities against breast (MCF-7) cancer cell line. After determination of the ineffective concentrations of compounds on the proliferation of MCF-7 cells, wound healing experiments were conducted to investigate the antimigratory effects of compounds. While compounds 4 and 10 had no effect on cell migration, treatment of MCF-7 cells with compounds 5, 8 and 9 resulted in significant reduction in cell motility. Taken together our results suggest that the newly synthesized compounds 5, 8 and 9 had the potential antimigratory activity through possible ROCK inhibition in cancer cells. (C) 2020 ACG Publications. All rights reserved.