El-Damasy, Ashraf Kareem Cho, Nam-Chul Pae, Ae Nim Kim, Eunice Eunkyeong Keum, Gyochang 2024-01-20T04:00:28Z 2024-01-20T04:00:28Z 2021-09-04 2016-07-15 0960-894X https://pubs.kist.re.kr/handle/201004/123871 A series of new 2-anilinoquinolines possessing 3-(morpholino or 4-methylpiperazin-1-yl) propoxy moiety at C5 of quinoline has been designed and synthesized as potential anticancer agents. Their antiproliferative activities were evaluated against a panel of 60 cancer cell lines at NCI and compared with gefitinib as a reference compound. Most of the tested compounds displayed potent and broad spectrum antiproliferative activities. Compounds 7d, 7f and 7g showed strong inhibitory and lethal effects at 10 mu M concentration. Moreover, they manifested superior potencies and efficacies than gefitinib across the most tested cell lines. Compound 7d, with 4-chloro-3-trifluoromethylphenyl group, proved to be the most potent and efficacious derivative in this series, with mean GI(50) and TGI values of 1.62 mu M and 3.47 mu M, respectively. Kinase screening of 7d against a panel of 47 oncogenic kinases revealed its selective inhibitory effect (96% inhibition) towards TrkA kinase. Furthermore, the most potent compounds showed low cytotoxic effects against HFF-1 normal cell line. (C) 2016 Elsevier Ltd. All rights reserved. English Pergamon Press Ltd. NERVE GROWTH-FACTOR ANTICANCER AGENTS TYROSINE KINASES BREAST-CANCER IN-VITRO PAN-TRK INHIBITOR DISCOVERY EXPRESSION POTENT Novel 5-substituted-2-anilinoquinolines with 3-(morpholino or 4-methylpiperazin-1-yl)propoxy moiety as broad spectrum antiproliferative agents: Synthesis, cell based assays and kinase screening Article 10.1016/j.bmcl.2016.05.047 1 Bioorganic & Medicinal Chemistry Letters, v.26, no.14, pp.3307 - 3312 Bioorganic & Medicinal Chemistry Letters 26 14 3307 3312 scie scopus 000377471400021 2-s2.0-84969964186 Chemistry, Medicinal Chemistry, Organic Pharmacology & Pharmacy Chemistry Article NERVE GROWTH-FACTOR ANTICANCER AGENTS TYROSINE KINASES BREAST-CANCER IN-VITRO PAN-TRK INHIBITOR DISCOVERY EXPRESSION POTENT 2-Anilinoquinolines Antiproliferative activity 3-(Morpholino)propoxy 3-(4-Methylpiperazin-1-yl)propoxy TrkA kinase