Synthesis of Novel Hybrid Heterocycles Tethered 2,3‐Diphenoxyquinoxaline Moiety via Hantzsch, Michael, and Biginelli Reactions: Antimicrobial Activities and Molecular Docking Simulation
Hadeer M. Diab, Doaa Hassan Ali, Tayseer A. Abdallah, Mona M. Soliman, Ahmed H. M. Elwahy, Ismail A. Abdelhamid, Mostafa E. Salem, Ibrahim M. Z. Fares
Abstract
ABSTRACT In this study, we have developed new hybrid compounds by connecting bis‐heterocycles with a 2,3‐diphenoxyquinoxaline core. This is performed by combining 4,4′‐(quinoxaline‐2,3‐diylbis(oxy))dibenzaldehyde with the necessary reagents via Hantzsch and Biginelli reactions. The newly synthesized compounds' structures are determined by elemental analysis, 1 H NMR, 13 C NMR, IR, and MS spectra. The tested compound 18 has the strongest antibacterial activities against S. aureus and E. coli , with inhibition zones of 18 and 14.67 mm, respectively. The tested compound 5 exhibited the strongest antibacterial activities against S. aureus , with an inhibition zone of 17 mm. Molecular docking studies of the most efficient compounds were performed against two proteins, including ATP‐dependent Clp protease ATP‐binding subunit ClpA (UniProt ID: P0ABH9) and Glycerol dehydrogenase (GDH) (UniProt ID: P0A9S5). Compound 5 interacted with the ClpA active site, exhibiting a binding score of ∆G = −9.2 Kcal/mol, while 18 interacted with the GDH active site, exhibiting a binding score of ∆G = −11.4 Kcal/mol.