Synthesis, In Vitro, and In Silico Approach to Quinoline-Arylsulfonate Derivatives as Antimicrobial Agents: DFT, Molecular Docking, and ADMET Studies

Abstract A series of novel 4-((7-chloroquinolin-4-yl)amino)phenyl arenesulfonates were synthesized via a two-step process and characterized by different spectroscopic technique for structural confirmation. The electronic structure of these derivatives was investigated by Density Functional Theory (DFT), a quantum mechanical method. All the derivatives were evaluated for their biological potency. The antibacterial activity was examined against a panel of bacteria, but they were found to be inactive. Antifungal examination demonstrated that these derivatives exhibited good to potent efficacy against fungal strain Candida albicans. Five derivatives had better MIC values between 125–250 μg/mL among all the synthesized compounds. These derivatives inhibited the formation and development of biofilms and other virulence factors of C. albicans such as adhesion and extracellular secreted proteinases and phospholipases. Furthermore, the result showed that these derivatives have low toxicity against human RBC cells. An in silico docking study showed a good binding energy with Als3 protein (PDB ID: 4LE8) and Sap2 protein (PDB ID: 1EAG) for 4-((7-chloroquinolin-4-yl)amino)phenyl 4-isopropylbenzenesulfonate and 4-((7-chloroquinolin-4-yl)amino)phenyl 4-methoxybenzenesulfonate. Considering the inhibitory effects of these derivatives against C. albicans, they can be used as potential candidates for antifungal development.