El-Gamal, Mohammed I. Khan, Mohammad Ashrafuddin Tarazi, Hamadeh Abdel-Maksoud, Mohammed S. El-Din, Mahmoud M. Gamal Yoo, Kyung Ho Oh, Chang-Hyun 2024-01-20T02:03:31Z 2024-01-20T02:03:31Z 2022-01-10 2017-02-15 0223-5234 https://pubs.kist.re.kr/handle/201004/123058 This article describes the design, synthesis, and biological screening of a new series of diarylurea derivatives possessing quinoline nucleus. Nine target compounds were selected by the National Cancer Institute (NCI, Bethesda, Maryland, USA) for in vitro antiproliferative screening against a panel of 58 cancer cell lines of nine cancer types. Following one-dose initial screening, compounds ld-g and 2b were selected for 5-dose screening in order to calculate their IC50 and total growth inhibition (TGI) values against the cell lines. Compounds le and lg were the most promising analogues. Both compounds showed strong potency and broad-spectrum antiproliferative activity against the different tested cancer types. Their IC50 and TGI values were less than those of the reference drug, sorafenib, against most of the tested cell lines of the nine different cancer types. Furthermore, the most potent compounds ld-g were tested against C-RAF kinase as a potential molecular target of this series of compounds. All of them showed high potency, and the most potent derivative was compound le (IC50 = 0.10 jiM). It was further tested against a panel of another twelve kinases, and it showed selectivity against C-RAF kinase. This could be, at least in part, the possible mechanism of antiproliferative action of this series of compounds at molecular level. The binding modes of compounds le and lg were studied by docking studies, which highlighted the importance of the urea linker compared with the amide linker. (C) 2017 Elsevier Masson SAS. All rights reserved. English ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER MELANOMA-CELL LINE PRELIMINARY CYTOTOXICITY EVALUATION SPECTRUM ANTICANCER AGENTS BIOLOGICAL EVALUATION 1,2,3-TRIAZOLE-4-CARBOXAMIDE MOIETY 1,3,4-TRIARYLPYRAZOLE SCAFFOLD PROSTATE-CANCER DIARYLAMIDES DISCOVERY EXPRESSION Design and synthesis of new RAF kinase-inhibiting antiproliferative quinoline derivatives. Part 2: Diarylurea derivatives Article 10.1016/j.ejmech.2017.01.006 1 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.127, pp.413 - 423 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 127 413 423 scie scopus 000397172800034 2-s2.0-85008889300 Chemistry, Medicinal Pharmacology & Pharmacy Article MELANOMA-CELL LINE PRELIMINARY CYTOTOXICITY EVALUATION SPECTRUM ANTICANCER AGENTS BIOLOGICAL EVALUATION 1,2,3-TRIAZOLE-4-CARBOXAMIDE MOIETY 1,3,4-TRIARYLPYRAZOLE SCAFFOLD PROSTATE-CANCER DIARYLAMIDES DISCOVERY EXPRESSION Antiproliferative activity C-RAF kinase Diarylurea Molecular docking Quinoline