Enzyme inhibition and antioxidant potential of new synthesized sulfonamides; synthesis, single crystal and molecular docking

This study describes the synthesis of four ( 1-4 ) new phenylalanine based sulfonamides from benzene sulfonyl chlorides. The progress of the reaction was monitored on TLC and after completion; the products were subjected to various analyses that indicated the synthesis of the targeted molecules. The structure of sulfonamide 1 was elucidated on the basis of Single Crystal X-Ray Diffraction technique. While other sulfonamides were characterized with FTIR spectroscopy. The sulfonamide ( 1-4 ) were subjected to Density Functional Theory for optimization of the structures and to calculate the bond angle and bond length of the crystalline molecule ( 1 ). The DFT and SCXRD results are in close agreement with each other. All compounds were subjected to radical scavenging and enzyme inhibition studies. The compound 1 exhibited moderate antioxidant activity (38.04 %). Enzyme inhibition potential was checked against three enzymes; trypsin, acetylcholine esterase and butyrylcholine esterase using in-vitro models. This study indicated that 2-(4-acetamidophenylsulfonamido)-3-phenylpropanoic acid ( 1 ) was found most active among all the synthetic molecules. It exhibited inhibition of 54.07%, 72.42and 57.18 % against AChE, BChE and trypsin respectively. Docking studies of the four sulfonamides were also done with Molecular Operating Environment, which depicted good docking scores. In-silico studies also suggested good enzyme inhibition potential of these understudied molecules. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

This study successfully synthesized four new phenylalanine-based sulfonamides and characterized and optimized them using FTIR spectroscopy, Density Functional Theory, and Single Crystal X-Ray Diffraction technique. Compound 1 exhibited high activity in antioxidant and enzyme inhibition, being the most active among all synthetic molecules.