{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T17:00:30Z","timestamp":1773075630368,"version":"3.50.1"},"reference-count":72,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    A series of pyrrolidine\u20102\u2010carbonitrile derivatives was designed, synthesized, and evaluated for their antidiabetic potential. The synthesized compounds exhibited notable inhibitory activity, with IC\u2085\u2080 values ranging from 9.36 to 21.54\u2009\u00b5g\/mL for\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010amylase, 13.32 to 46.14\u2009\u00b5g\/mL for\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010glucosidase, and 22.87 to 42.12\u2009\u00b5g\/mL for DPP\u2010IV. Among the evaluated derivatives, compounds bearing para\u2010methyl (\n                    <jats:bold>6b<\/jats:bold>\n                    ) and para\u2010chloro (\n                    <jats:bold>6c<\/jats:bold>\n                    ) substituents demonstrated the most potent inhibitory activity across all three enzymatic targets. To elucidate the underlying trends, a SAR analysis was conducted, revealing that both electronic properties and steric effects of the substituents significantly influenced enzyme inhibition potency. The molecular docking studies showed strong and specific interactions between the active compounds and key residues within the catalytic sites of the target enzymes. In addition, UV\u2010visible absorption and fluorescence spectroscopy studies demonstrated high binding affinities for both\n                    <jats:bold>6b<\/jats:bold>\n                    and\n                    <jats:bold>6c<\/jats:bold>\n                    with HSA, having binding constant (K\n                    <jats:sub>a<\/jats:sub>\n                    ) values of 7.31\u2009\u00d7\u200910\u2075\u2009M\u207b\u00b9 and 7.43\u2009\u00d7\u200910\u2075\u2009M\u207b\u00b9, respectively. Taken together, these findings highlight compounds 6b and 6c as promising lead candidates for the development of multitarget antidiabetic agents.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70170","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T09:15:09Z","timestamp":1758878109000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pyrrolidine\u20102\u2010carbonitrile Derivatives as Multifunctional Antidiabetic Agents: Inhibition of\n                    <i>\u03b1<\/i>\n                    \u2010Amylase,\n                    <i>\u03b1<\/i>\n                    \u2010Glucosidase, and DPP\u2010IV With Structure\u2010Activity Relationships, HSA Binding, and Molecular Docking Studies"],"prefix":"10.1002","volume":"86","author":[{"given":"Aeyaz Ahmad","family":"Bhat","sequence":"first","affiliation":[{"name":"Department of Chemistry, School of Chemical Engineering and Physical Sciences Lovely Professional University Phagwara India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2838-1741","authenticated-orcid":false,"given":"Iqubal","family":"Singh","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Lovely Professional University Phagwara India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389201017666160808160513"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28072979"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2023.124656"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-021-00597-z"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e39444"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202103757"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2011.07.005"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)91416-J"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rineng.2023.101335"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2018.02.023"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/07853899708999371"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13197-021-05231-0"},{"key":"e_1_2_9_14_1","first-page":"26","article-title":"\u03b1\u2010 Amylase Inhibition Activity of Some Plants Extract of Teucrium Species","volume":"7","author":"Dastjerdi Z. 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