title: Synthesis and broad-spectrum antiproliferative activity of diarylamides and diarylureas possessing 1,3,4-oxadiazole derivatives.
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.
authors: Center 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.
authors: Mahmoud M
authors: MM
authors: Gamal El-Din
authors: Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
authors: Mohammed I
authors: MI
authors: El-Gamal
authors: Center 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.
authors: Mohammed S
authors: MS
authors: Abdel-Maksoud
authors: Chemical Kinomics Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea.
authors: Kyung Ho
authors: KH
authors: Yoo
authors: Center 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. Electronic address: choh@kist.re.kr.
authors: Chang-Hyun
authors: CH
authors: Oh
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D009536:Niacinamide / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D010069:Oxadiazoles / Q000737:chemistry*; D010671:Phenylurea Compounds / Q000737:chemistry / Q000494:pharmacology; D000077157:Sorafenib; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D010069:Oxadiazoles; D010671:Phenylurea Compounds; C583463:1,3,4-oxadiazole; D009536:Niacinamide; D014508:Urea; D000077157:Sorafenib
keywords: 1,3,4-Oxadiazole; Antiproliferative activity; Diarylamides; Diarylureas