{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:03:24Z","timestamp":1780470204908,"version":"3.54.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Type 2 diabetes has become one of the most common causes of human deaths. Key factors that contribute to the progression of this disease include a sedentary lifestyle, high-fat diet, and genetic abnormalities. Enzyme PTP1B is an important target for researchers as it plays a vital role in performing normal metabolic functions of the human body. Metabolic diseases such as obesity, type 2 diabetes, and cardiovascular complications are due to PTP1B imbalance. It is evident that the overproduction of PTP1B is a prominent factor contributing to the onset and progression of type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Multiple attempts have been made in recent years to synthesize PTP1B inhibitors but, in most cases, complications were associated with the selectivity and toxicity of the synthesized analogs, which resulted in the failure of their clinical trials. This study comprises a series of ondansetron derivatives, which were developed by employing a one-pot (reductive amination) reaction between ondansetron and substituted anilines to synthesize primary amines as final products. These final products (ondansetron derivatives) were analyzed as PTP1B inhibitors to study the role of enzyme PTP1B in lowering blood glucose levels in conditions such as type 2 diabetes. These novel compounds can provide valuable insights into the development of improved treatment options for diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The synthesized PTP1B inhibitors were subject to\n                      <jats:italic>in silico<\/jats:italic>\n                      ,\n                      <jats:italic>in vitro<\/jats:italic>\n                      , and\n                      <jats:italic>in vivo<\/jats:italic>\n                      analysis that revealed encouraging results. The computational data of the selected ligand FN-06 showed highest binding affinity, with the protein PTP1B (1T48) having a docking score of \u22127.317\u00a0kcal\/mol. The indicators of the simulation also reflected the stability of the said ligand. Similarly, the results of an\n                      <jats:italic>in vitro<\/jats:italic>\n                      inhibition assay further confirmed that the synthesized compound FN-10 showed direct inhibition of the enzyme PTP1B. Furthermore, animal studies demonstrate the hepatoprotective and anti-diabetic action of the selected compounds FN-06 and FN-10 along with the parent compound ondansetron.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The findings of this study suggest that compounds FN-06 and FN-10 may act as lead structures to design potent derivatives, which have antidiabetic activity with hepatoprotective effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1796359","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:06:36Z","timestamp":1780466796000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ondansetron derivatives as potential PTP1B inhibitors for treating type 2 diabetes mellitus: in silico, in vitro, and in vivo analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Fawad","family":"Naeem","sequence":"first","affiliation":[{"name":"Riphah Institute of Pharmaceutical Sciences, Riphah International University","place":["Islamabad, Pakistan"]},{"name":"Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University","place":["Islamabad, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Central Hospital of Dalian University of Technology","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafeez Mujtaba","family":"Babar","sequence":"additional","affiliation":[{"name":"Riphah Institute of Pharmaceutical Sciences, Riphah International University","place":["Islamabad, Pakistan"]},{"name":"Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University","place":["Islamabad, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Haroon","family":"Hussain","sequence":"additional","affiliation":[{"name":"Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University","place":["Islamabad, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaman","family":"Ashraf","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Rawalpindi Women University","place":["Rawalpindi, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Sun","sequence":"additional","affiliation":[{"name":"Central Hospital of Dalian University of Technology","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohaib","family":"Zafar","sequence":"additional","affiliation":[{"name":"Riphah Institute of Pharmaceutical Sciences, Riphah International University","place":["Islamabad, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Central Hospital of Dalian University of Technology","place":["Dalian, China"]},{"name":"Faculty of Medicine, Dalian University of Technology","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3849","DOI":"10.1021\/jo960057x","article-title":"Reductive amination of aldehydes and ketones with sodium triacetoxyborohydride. 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