Pro-Gly based dipeptide containing sulphonamide functionality, their antidiabetic, antioxidant, and anti-inflammatory activities. Synthesis, characterization and computational studies

The increasing resistance to antidiabetic, antioxidant, and anti-inflammatory drugs are complex and severe health issues these days, as many drugs available on the market are no more effective. The choice for the synthesis of novel dipeptides-sulphonamide hybrid is based on their wide biological properties such as antidiabetic, antioxidant, antimalarial, etc. The base promoted reactions of the L-proline with substituted benzenesulphonyl chloride gave benzenesulphonamides an excellent yield. The condensation reaction of benzenesulphonamides with the carboxamide derivatives using peptide coupling reagents gave targeted products (8a-j). The ten novel compounds were characterized using 1HNMR, 13CNMR, FTIR, and MS spectroscopic techniques. The DFT and in-silico antidiabetic, antioxidant and anti-inflammatory studies showed good interactions of the compounds with target protein residues and a higher dock score in comparison with standard drugs. In vivo antidiabetic, anti-inflammatory and in vitro antioxidant activities were also studied. Estimation of glucose, cholesterol and triacylglycerol levels was carried out and it was observed that compound 8a exhibited significant antidiabetic activity. Compounds 8b, 8c, and 8d also possessed moderate antidiabetic activity. In the in vivo anti-inflammatory studies, compounds 8a inhibited carrageenan-induced rat-paw edema at 94.67 and 91.88% at 0.5 h, and 1 h administration respectively. Compound 8a had excellent antioxidant activity. Compound 8a with IC50 of 0.992 μg/ml is comparable with that of ascorbic acid at 0.993 μg/ml. This implies that compound 8a can serve as an antioxidant agent compared with ascorbic acid. Calculated DFT parameters agreed significantly with the antidiabetic and anti-inflammatory studies