Synthesis of sustainable heterocyclic aryl sulfonamide derivatives: computational studies, molecular docking, and antibacterial assessment

The treatment of infectious diseases is impacted by the emergence of multidrug-resistant microbiological infections. Due to the long-term usage of antibacterial clinical drugs, microbes develop resistance to clinical drugs. To take advantage of the potential of these families of chemicals, several derivatives of thiophene containing p-toluene sulfonamide (TPS) were prepared using an eco-friendly method with high yields. These synthetic derivatives had a wide range of structural diversity to demonstrate a structure–activity link. In multi-component reaction (MCR), the versatile reactants (1 mmol) react for up to 6–8 h at pH 7.2 ± 0.2 and temperature 70 ± 1 °C. The reaction involved the reusable organic catalyst l-Proline (1 mol%), and the mechanisms through a Knoevenagel condensation pathway, which has the advantage of effectively producing the described thiophene derivatives (TD). Then, further TD reacts with p-toluene sulfonamide (Tosyl-Cl) at 0 °C within 10–12 h to provide the final product TPS. The present investigation provides an inexpensive and eco-friendly method of TPS derivatives. A perusal of the tables indicates that TPS derivatives exhibited promising activity against S. typhimurium as compared to E. coli and S. aureus. The compounds having good activity contained electron-withdrawing as well as electron-donating substituent groups on the benzaldehyde benzene ring of the amino part of the amide.

Graphical abstract

Green sustainable development of multi component heterocyclic aryl sulfonamide reaction