One-pot synthesis of new bis(2,4′-bipyridine), bis(pyrrole), and bis(benzo (f)chromene) derivatives: Antimicrobial evaluation, molecular docking, DFT, and ADME profiling

Abstract

Given the reported biological activities of bis(heterocycles), some new bis(2,4′-bipyridine), bis(pyrrole), and bis (benzo[f]chromene) have been constructed using a one-pot synthetic method. Several spectral tools elucidated their chemical structures. Computational chemical analyses, including Fukui functions, frontier molecular orbitals (HOMO–LUMO), molecular electrostatic potential (MEP), and Mulliken charge distribution, were performed to evaluate the electronic structure and reactivity of synthesized compounds. Bis(benzo[f]chromene) 20 exhibited the lowest HOMO–LUMO energy gap (3.397 eV), highest softness (0.589 eV), and pronounced negative electrostatic regions around nitrogen atoms, suggesting enhanced reactivity and consistent with its high biological activity. In vitro antimicrobial properties of new compounds were also assessed, and the results indicated potent activity of compound 20 against Candida albicans and Staphylococcus aureus. This study also investigated the pharmacological potential of 20 through docking interactions with two critical protein targets - MurB (PDB ID: 1HSK) from Staphylococcus aureus and the 80S ribosome (PDB ID: 9G1Z) from Candida Albicans. Benchmark ligands FAD and YMZ (mefloquine) were used for comparative docking. Despite its limited oral absorption and solubility revealed by pharmacokinetic analysis, the compound demonstrated favorable drug-likeness, synthetic accessibility, and a lack of toxicity. These attributes support its consideration as a lead compound for further development and synthetic accessibility.