Design and synthesis of pyrimidine molecules endowed with thiazolidin-4-one as new anticancer agents

Eur J Med Chem. 2014 Aug 18:83:630-45. doi: 10.1016/j.ejmech.2014.06.033. Epub 2014 Jun 17.

Abstract

Design and synthesis of new pyrimidine derivatives clubbed with thiazolidin-4-one from 4-(2-chlorophenyl)-6-(2,4-dichlorophenyl)pyrimidin-2-amine and their in vitro anticancer activities were screened at National Cancer Institute (NCI), USA against full NCI 60 cell lines. Compound 2 (NSC: 765735) exhibited remarkable growth inhibition at single dose (10 μM) and encourage chosen for broadcast at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 μM). The compound 2 was found better quality for Lung cancer cell line (HOP-92) by viewing growth inhibition (GI50 0.52) and no cytotoxicity seen (LC50 > 100). Molecular docking study was performed using Maestro 9.0 (Schrodinger Inc. USA) to provide binding mode into binding sites of CDK2. Compound 2 could be used as a lead compound for developing new potential anticancer agents.

Keywords: CDK 2 enzyme; In-vitro anticancer activity; NCI 60 cell line; Thiazolidin-4-one.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Chemistry Techniques, Synthetic
  • Cyclin-Dependent Kinase 2 / chemistry
  • Cyclin-Dependent Kinase 2 / metabolism
  • Drug Design*
  • Humans
  • Molecular Docking Simulation
  • Protein Conformation
  • Structure-Activity Relationship
  • Thiazolidines / chemical synthesis*
  • Thiazolidines / chemistry
  • Thiazolidines / metabolism
  • Thiazolidines / pharmacology*

Substances

  • Antineoplastic Agents
  • Thiazolidines
  • Cyclin-Dependent Kinase 2