Synthesis and broad-spectrum antiproliferative activity of diarylamides and diarylureas possessing 1,3,4-oxadiazole derivatives

A series of diarylamides and diarylureas possessing 1,3,4-oxadiazole scaffold was designed and synthesized. Their in vitro antiproliferative activities were tested against a panel of 58 cell lines of nine different cancer types at the NCI, and compared with Sorafenib as a reference compound. Most of the compounds showed strong and broad-spectrum antiproliferative activities. The diarylurea compound 2g possessing 4-chloro-3-(trifluoromethyl)phenyl terminal moiety showed the highest mean % inhibition value of about 100% over the 58-cell line panel at 10 μM concentration. Also compounds 2h, 2l, 2m exhibited mean % inhibition over 90% at 10 μM concentration. The IC50 value of compound 2b over SNB-75 CNS cancer cell line was 0.65 μM. Compound 2h also exerted submicromolar IC50 values of 0.67, 0.80, and 0.87 μM against PC-3 prostate cancer cell line, HCT-116 colon cancer cell line, and ACHN renal cancer cell line, respectively. Compound 2h showed comparable efficacy to Sorafenib.

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