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From a library of compounds synthesized, 1\u2010(2\u2010(4\u2010(7\u2010Chloro\u20104\u2010quinolyl)piperazin\u20101\u2010yl)acetyl)pyrrolidine (<jats:bold>2g<\/jats:bold>) was identified as a potential <jats:styled-content style=\"fixed-case\">DPP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> inhibitor exhibiting better inhibitory activity than P32\/98, reference inhibitor. The <jats:italic>in vivo<\/jats:italic> studies carried out in <jats:styled-content style=\"fixed-case\">STZ<\/jats:styled-content> and <jats:italic>db\/db<\/jats:italic> mice models indicated that the compound <jats:bold>2g<\/jats:bold> showed moderate antihyperglycemic activity as compared to the marketed drug Sitagliptin. A two\u2010week repeated dose study in <jats:italic>db\/db<\/jats:italic> mice revealed that compound <jats:bold>2g<\/jats:bold> 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 <jats:bold>2g<\/jats:bold> at the <jats:styled-content style=\"fixed-case\">DPP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> active site and are in favor of the observed biological data. These data collectively suggest that compound <jats:bold>2g<\/jats:bold> is a good lead molecule for further optimization studies.<\/jats:p>","DOI":"10.1111\/cbdd.12426","type":"journal-article","created":{"date-parts":[[2014,9,12]],"date-time":"2014-09-12T11:24:51Z","timestamp":1410521091000},"page":"439-446","source":"Crossref","is-referenced-by-count":20,"title":["Design, Synthesis, Biological Screening, and Molecular Docking Studies of Piperazine\u2010Derived Constrained Inhibitors of DPP\u2010IV for the Treatment of Type 2 Diabetes"],"prefix":"10.1111","volume":"85","author":[{"given":"Ram N.","family":"Kushwaha","sequence":"first","affiliation":[{"name":"Medicinal and Process Chemistry Division CSIR\u2010Central Drug Research Institute Sector 10 Jankipuram Extension Lucknow 226031 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rohit","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Biochemistry Division CSIR\u2010Central Drug Research 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