Anticancer profile of newly synthesized BRAF inhibitors possess 5-(pyrimidin-4-yl)imidazo[2,1-b]thiazole scaffold |
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| Authors: | Mohammed S Abdel-Maksoud Usama M Ammar Chang-Hyun Oh |
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| Institution: | 1. Medicinal & Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Dokki, Giza 12622, Egypt;2. Center for Biomaterials, Korea Institute of Science & Technology (KIST School), Seoul, Seongbuk-gu 02792, Republic of Korea;3. University of Science & Technology (UST), Daejeon, Yuseong-gu 34113, Republic of Korea;4. Department of Biomolecular Science, University of Science & Technology (UST), Daejeon, Yuseong-gu 34113, Republic of Korea;5. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ahram Canadian University, Giza 12566, Egypt |
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| Abstract: | In this work, a new series of imidazo2,1-b]thiazole was designed and synthesized. The new compounds are having 3-fluorophenyl at position 6 of imidazo2,1-b]thiazole and pyrimidine ring at position 5. The pyrimidine ring containing either amide or sulphonamide moiety attached to a linker (ethyl or propyl) at position 2 of the pyrimidine ring. The final compounds were selected by NCI for in vitro cytotoxicity screening. Most derivatives showed cytotoxic activity against colon cancer and melanoma cell lines. In addition, IC50s of the target compounds were determined over A375 and SK-MEL-28 cell lines using sorafenib as positive control. Compounds12b, 12c, 12e, 12f, 15a, 15d, 15f, 14g and 15h exhibited superior activity when compared to sorafenib. The most potent compounds were tested against wild type BRAF, v600e BRAF, and CRAF. Compound 15h exhibited a potential inhibitory effect againstV600EBRAF (IC50?=?9.3?nM). |
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| Keywords: | Anticancer Colon cancer Melanoma BAF inhibitors |
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