New triarylpyrazoles as broad-spectrum anticancer agents: design, synthesis, and biological evaluation.

Abstract

A new series of diarylureas and diarylamides possessing 1,3,4-triarylpyrazole scaffold was designed and synthesized. Their in vitro antiproliferative activities against NCI-60 cell line panel were tested. Most of the compounds showed strong and broad-spectrum antiproliferative activities. Compound 18 exerted sub-micromolar IC50 values over all the subpanels of nine different cancer types. Its IC50 value over MDA-MB-435 melanoma cell line was 27 nM. Compounds 10-13, 22, and 23 possessing urea spacer exerted lethal effect over the NCI-60 panel with mean %inhibitions more than 100% in single-dose testing. Compounds 13 and 23 with urea linker and 3',5'-bis(trifluoromethyl)phenyl terminal ring showed the highest mean %inhibition over the NCI-60 panel in single-dose testing, and showed high potencies and broad-spectrum anticancer activities in five-dose testing.

• Authors: Mohammed I El-Gamal, Yi Seul Park, Dae Yoon Chi, Kyung Ho Yoo, Chang-Hyun Oh
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 65 Pg. 315-22 (Jul 2013) ISSN: 1768-3254 [Electronic] France
• PMID: 23732996 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Pyrazoles

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Design
• Humans
• Molecular Structure
• Pyrazoles (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship