Novel piperazine-derived conformationally constrained compounds were designed, synthesized, and evaluated for in vitro Dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. From a library of compounds synthesized, 1-(2-(4-(7-Chloro-4-quinolyl)piperazin-1-yl)acetyl)pyrrolidine (2g) was identified as a potential DPP-IV inhibitor exhibiting better inhibitory activity than P32/98, reference inhibitor. The in vivo studies carried out in STZ and db/db mice models indicated that the compound 2g showed moderate antihyperglycemic activity as compared to the marketed drug Sitagliptin. A two-week repeated dose study in db/db mice revealed that compound 2g significantly declined blood glucose levels with no evidence of hypoglycemia risk. Furthermore, it showed improvement in insulin resistance reversal and antidyslipidemic properties. Molecular docking studies established good binding affinity of compound 2g at the DPP-IV active site and are in favor of the observed biological data. These data collectively suggest that compound 2g is a good lead molecule for further optimization studies.

Antimicrobial activities of (-)-catechin derivatives were assayed for their antibacterial and antifungal activities against gram positive, gram negative bacteria, and fungi. Most of the compounds significantly active among which Compounds 1a, 1b, and 1c showed excellent antibacterial for both gram negative and gram positive bacteria, these compounds also exhibited excellent antifungal activity more than the standard drug. Molecular docking studies of Compounds 1a and 1b established good binding affinity with ATP-binding pocket of DNA gyrase and are in favor of the observed biological activity. These data collectively suggest that Compounds 1a and 1b could serve as a novel antimicrobial agent.