New furochromone derivatives as promising in-vitro anti-proliferative agents toward HepG-2 and MCF-7 cell lines with molecular docking studies |
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Authors: | Nagwa M Fawzy Khadiga M Ahmed Heba M Abo-Salem Magdy S Aly |
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Institution: | 1. Chemistry of Natural and Microbial Products Department, National Research Center, Giza, Egypt;2. Chemistry of Natural Compounds Department, National Research Centre, Giza, Egypt;3. Genetics Branch, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt |
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Abstract: | Based on the considerable features of the multicomponent reactions (MCRs) in the field of organic and medicinal chemistry, the present work was designed to synthesize a new series of imidazole, pyridine, and pyrimidine derivatives using MCRs to obtain new anti-proliferative agent beside exploration of their interaction mechanism by molecular docking technique. MCRs of furochromone carbaldehyde 1 , benzoin, and ammonium acetate afforded the corresponding 2,4,5-trisubstituted imidazole 2 . However, MCRs of 1 with benzoin, amine derivatives, and ammonium acetate yielded the corresponding 1,2,4,5-tetrasubstituted imidazole 3a,b . In addition, pyridine 4a,b-5a,b and pyrimidine derivatives 6a,d were synthesized via condensation of 1 with different carbonyl compounds and ammonium acetate or benzyl urea, respectively. The in-vitro anti-Proliferative activities of the new furochromone derivatives were screened toward MCF-7 and HepG-2 cancer cell lines as well as the normal cell line (human normal melanocyte, HFB4) in comparison to the known anticancer drugs: 5-fluorouracil and doxorubicin using MTT assay. Compounds 5a and 5b revealed effective anti-proliferative activity against MCF-7 cell lines with IC 50 18 and 22 μg/mL, respectively, compared to 5-fluorouracil (IC 50 of 13 μg/mL). However, compounds 6a-d exhibited potent activity against HepG-2 cancer cell lines of IC 50 ranging from 18 to 20 μg/mL compared to doxorubicin (IC 50 of 14 μg/mL). Moreover, the binding mode of the most active furochromones 5a,b and 6a-d inside the active site of the epidermal growth factor receptor (EGFR) kinase enzyme (PDB ID: 5CAV) were studied using molecular docking technique. Compounds 6b,c showed excellent docking results compared to the known EGFR inhibitors ( 4ZQ ). |
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