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

• New diarylureas and diarylamides with 1,3,4-triarylpyrazole scaffold were synthesized.
• Their in vitro antiproliferative activities against NCI-60 cancer cell line panel were tested.
• Compounds 10–13, 22, and 23 exerted lethal effect over NCI-60 panel with mean %inhibitions >100%.
• Most of the compounds showed sub-micromolar IC50 values.
• The IC50 value of compound 18 over MDA-MB-435 melanoma cell line was 27 nM.

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.

Design, synthesis, and in vitro antiproliferative activities of a new series of diarylureas and diarylamides possessing 1,3,4-triarylpyrazole scaffold are reported.Figure optionsDownload as PowerPoint slide