N-acylated and N,N'-diacylated imidazolidine-2-thione derivatives and N,N'-diacylated tetrahydropyrimidine-2(1H)-thione analogues: synthesis and antiproliferative activity

Eur J Med Chem. 2009 Mar;44(3):1106-18. doi: 10.1016/j.ejmech.2008.06.010. Epub 2008 Jun 24.

Abstract

Fifty-one acylthioureas (ATUs) incorporating imidazolidine-2-thione or its upper cyclohomologue were prepared by parallel synthesis and evaluated against a high number of human cancer cell lines for antiproliferative activity. ATUs 1o (3,5-dichlorobenzoyl), 1s (2-furoyl), 3s (2-furoyl) and 1t (2-thenoyl) displayed activity against leukemia, melanoma LOX IMVI, non-small cell lung NCI-H522, renal 786-0, CAKI-1, SN12C, UO-31 and breast MCF7, MDA-MB-435, T-47D cancer cell lines in the 0.3-9.7 microM concentration range. Compound 14s exhibited selectivity for melanoma SK-MEL-5 (GI(50)<5 nM); 1s for leukemia MOLT-4 (GI(50): 300 nM); 1q, 3b and 3q for renal cancer UO-31 (GI(50): 70-200 nM); 8s, 9s for non-small cell lung cancer EKVX (GI(50): 300, 10 nM) and 3j for HOP-92 (GI(50): 700 nM) cell line.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Drug Screening Assays, Antitumor
  • Humans
  • Imidazolidines / chemical synthesis*
  • Imidazolidines / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / pharmacology*
  • Spectrophotometry, Infrared

Substances

  • Imidazolidines
  • Pyrimidines