GREEN SYNTHESIS, COMPUTER-AIDED DRUG DESIGN, PHYSICOCHEMICAL, AND ADMET PROPERTIES OF NOVEL SULFONAMIDES AS POTENTIAL ANTIMICROBIAL DRUGS

For the first time, sulfonamides bearing thiomorpholine were synthesized by a facile single-step process in good to excellent yields (82-94%). All the compounds were screened for in vitro antimicrobial activities. Results demonstrated that 3a, 3c and 3d promising antimicrobial activities against the screened bacterial and fungal strains when compared with the standard drugs streptomycin and ketoconazole at 12.5, 25, 50 and 100 µg/mL concentrations. This synthetic protocol provides a simple work-up procedure, excellent yields, shorter reaction times, low cost of starting substrates, and pharmacologically important new antimicrobial drugs. These drugs might be a promising drug candidate for further investigation. In silico molecular screening of these compounds gave an insight of drug-receptor interaction of synthesized novel six sulfonamides bearing thiomorpholine. These derivatives were analyzed for antimicrobial activity via in silico and in vitro studies. Physicochemical studies and BOILED- egg model ((the Brain Or IntestinaL EstimateD permeation method) were evaluated. All derivatives fall under RO5 rule (Lipinski rule of five). They showed zero violations whereas, marketed drugs showed three violations (streptomycin) and one violation (ketoconazole). They all showed good oral drug bioavailability, good drug likeness and very low toxicity. Molecular docking results have been focused on high full fitness score, deltaG and binding energies against antimicrobial targets (PDB: 2VF5, 1KZN and 1JIJ) which gave an insight of drug-receptor interaction of synthesized novel six sulfonamide derivatives. They have been systematically docked with three antimicrobial protein targets (PDB: 2VF5, 1JIJ and 1KZN). As full fitness score, hydrogen binding interactions, binding energy modes and DeltaG value are the main parameters for evaluating the molecular docking studies and evaluation of drug target interactions. All screened derivatives exhibited strong interactions with the respective protein targets, they showed maximum full fitness score, binding energy modes and DeltaG values. The modified scaffolds exhibited higher efficacy over sulfonamides. These drugs might be a promising drug candidate for further investigation. Pour la première fois, des sulfonamides portant de la thiomorpholine ont été synthétisés à travers un procédé facile en une seule étape en rendements bons à excellents (82 à 94 %). Tous les composés ont été criblés pour des activités antimicrobiennes