Pyrrolo[3,2-c]pyridine derivatives with potential inhibitory effect against FMS kinase: in vitro biological studies |
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Authors: | Mohammed I El-Gamal |
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Institution: | 1. Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, United Arab Emirates;2. Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates;3. Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura, Egypt |
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Abstract: | A series of eighteen pyrrolo3,2-c]pyridine derivatives were tested for inhibitory effect against FMS kinase. Compounds 1e and 1r were the most potent among all the other tested analogues (IC50?=?60?nM and 30?nM, respectively). They were 1.6 and 3.2 times, respectively, more potent than our lead compound, KIST101029 (IC50?=?96?nM). Compound 1r was tested over a panel of 40 kinases including FMS, and exerted selectivity against FMS kinase. It was further tested against bone marrow-derived macrophages (BMDM) and its IC50 was 84?nM (2.32-fold more potent than KIST101029 (IC50?=?195?nM)). Compound 1r was also tested for antiproliferative activity against a panel of six ovarian, two prostate, and five breast cancer cell lines, and its IC50 values ranged from 0.15–1.78?µM. It possesses also the merit of selectivity towards cancer cells than normal fibroblasts. |
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Keywords: | CSF-1R FMS kinase inhibition pyrrolo[3 2-c]pyridine |
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