Anbar, Hanan S. El-Gamal, Mohammed, I Tarazi, Hamadeh Lee, Bong S. Jeon, Hong R. Kwon, Dow Oh, Chang-Hyun 2024-01-19T18:30:52Z 2024-01-19T18:30:52Z 2021-09-05 2020-01-01 1475-6366 https://pubs.kist.re.kr/handle/201004/119104 A series of imidazothiazole derivatives possessing potential activity against melanoma cells were investigated for molecular mechanism of action. The target compounds were tested against V600E-B-RAF and RAF1 kinases. Compound1zbis the most potent against both kinases with IC(50)values 0.978 and 8.2 nM, respectively. It showed relative selectivity against V600E mutant B-RAF kinase. Compound1zbwas also tested against four melanoma cell lines and exerted superior potency (IC(50)0.18-0.59 mu M) compared to the reference standard drug, sorafenib (IC(50)1.95-5.45 mu M). Compound1zbdemonstrated also prominent selectivity towards melanoma cells than normal skin cells. It was further tested in whole-cell kinase assay and showed in-cell V600E-B-RAF kinase inhibition with IC(50)of 0.19 mu M. Compound1zbinduces apoptosis not necrosis in the most sensitive melanoma cell line, UACC-62. Furthermore, molecular dynamic and 3D-QSAR studies were done to investigate the binding mode and understand the pharmacophoric features of this series of compounds. English TAYLOR & FRANCIS LTD VITRO ANTICANCER EVALUATION ANTIPROLIFERATIVE ACTIVITY ANTITUMOR-ACTIVITY DERIVATIVES PERMEATION PATHWAY DESIGN SERIES VEGA Imidazothiazole-based potent inhibitors of V600E-B-RAF kinase with promising anti-melanoma activity: biological and computational studies Article 10.1080/14756366.2020.1819260 1 JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, v.35, no.1, pp.1712 - 1726 JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY 35 1 1712 1726 scie scopus 000571893800001 2-s2.0-85091553989 Biochemistry & Molecular Biology Chemistry, Medicinal Biochemistry & Molecular Biology Pharmacology & Pharmacy Article VITRO ANTICANCER EVALUATION ANTIPROLIFERATIVE ACTIVITY ANTITUMOR-ACTIVITY DERIVATIVES PERMEATION PATHWAY DESIGN SERIES VEGA Apoptosis imidazothiazole melanoma modelling V600E-B-RAF