El-Din, Mahmoud M. Gamal El-Gamal, Mohammed I. Abdel-Maksoud, Mohammed S. Yoo, Kyung Ho Baek, Daejin Choi, Jungseung Lee, Huiseong Oh, Chang-Hyun 2024-01-20T02:34:11Z 2024-01-20T02:34:11Z 2022-01-10 2016-12 1475-6366 https://pubs.kist.re.kr/handle/201004/123346 A novel series of substituted pyrimidine compounds bearing N-phenylpyrazole and terminating with aryl and cyclic sulfonamido moiety were designed, synthesized, and evaluated in vitro as antiproliferative agents against a panel of 53 cell lines of different tissues at the NCI. Among them, compound 1d with p-chlorobenzenesulfonamido terminal moiety, ethylene spacer, and 4-chloro-3-methoxyphenyl ring at position 3 of the pyrazole nucleus showed the highest mean percentage inhibition value over the whole cancer cell line panel at 10M concentration. It showed broad-spectrum antiproliferative activity over many cell lines of different cancer types. For instance, compound 1d inhibited the growth of HL-60 (TB), SR leukemia, and T-47D and MCF-7 breast cancer cell line by 135.92%, 119.44%, 95.32%, and 82.03% at 10M, respectively. And it inhibited the growth of COLO 205 colon, HT29 colon, BT-549 breast, and ACHN renal cancer cell lines by more than 80% at the same test concentration. However, testing compound 1d upon determining its IC50 against the most sensitive cell lines showed to good extent selectivity against HT29 colon cancer cell line than HL-60 leukemia and MRC-5 lung fibroblasts (normal cells). Compound 1d was further tested against 12 kinases of different kinase families, and the highest inhibitory effect was exerted against RAF1, V600E-B-RAF, and V600K-B-RAF kinases. English TAYLOR & FRANCIS LTD CANCER ANTICANCER DISCOVERY PATHWAY BEARING SERIES Design, synthesis, and in vitro antiproliferative and kinase inhibitory effects of pyrimidinylpyrazole derivatives terminating with arylsulfonamido or cyclic sulfamide substituents Article 10.1080/14756366.2016.1190715 1 JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, v.31, pp.111 - 122 JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY 31 111 122 scie scopus 000390410800014 2-s2.0-84976328244 Biochemistry & Molecular Biology Chemistry, Medicinal Biochemistry & Molecular Biology Pharmacology & Pharmacy Article CANCER ANTICANCER DISCOVERY PATHWAY BEARING SERIES Antiproliferative activity arylsulfonamide 1 3 4-triarylpyrazole RAF kinases