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

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.

• Authors: Sara Cesarini, Andrea Spallarossa, Angelo Ranise, Silvia Schenone, Camillo Rosano, Paolo La Colla, Giuseppina Sanna, Bernardetta Busonera, Roberta Loddo
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 44 Issue 3 Pg. 1106-18 (Mar 2009) ISSN: 1768-3254 [Electronic] France
• PMID: 18667259 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Imidazolidines
• Pyrimidines

Topics

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