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Published on: June 23, 2019
Synthesis and broad-spectrum antiproliferative activity of diarylamides and diarylureas possessing 1,3,4-oxadiazole
Mahmoud M Gamal El-Din1, Mohammed I El-Gamal2, Mohammed S Abdel-Maksoud1
1Center for Biomaterials, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea; Department of Biomolecular Science, University of Science and Technology, 113 Gwahangno, Yuseong-gu, Daejeon 305-333, Republic of Korea; Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki-Giza 12622, Egypt.
Abstract:
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 10μM concentration. Also compounds 2h, 2l, 2m exhibited mean % inhibition over 90% at 10μM concentration. The IC50 value of compound 2b over SNB-75 CNS cancer cell line was 0.65μM. Compound 2h also exerted submicromolar IC50 values of 0.67, 0.80, and 0.87μM 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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