New furochromone derivatives as promising in‐vitro anti‐proliferative agents toward HepG‐2 and MCF‐7 cell lines with molecular docking studies

• Published in: Journal of heterocyclic chemistry 2020-07, Vol.57 (7), p.2748-2761
• Main Authors: Fawzy, Nagwa M., Ahmed, Khadiga M., Abo‐Salem, Heba M., Aly, Magdy S.
• Format: Article
• Language: English
• Subjects: Ammonium acetate; Antiproliferatives; Benzoin; Biotechnology; Carbonyl compounds; Carbonyls; Derivatives; Doxorubicin; Growth factors; Imidazole; Kinases; Molecular docking
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.3984

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).