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The excessive PEP expression in brain results in neurodegenerative illnesses like dementia, Alzheimer\u2019s disease, and Parkinson's disease. Results of the prior studies on antioxidant activity, and the non-cytotoxic effect of bi-carbazole-linked triazoles, encouraged us to extend our studies towards its anti-diabetic potential. Hence, for this purpose all compounds <jats:bold>1<\/jats:bold>\u2013<jats:bold>9<\/jats:bold> were evaluated to reveal their anti-prolyl endo peptidase activity. Fortunately, seven compounds resulted into significant inhibitory capability ranging from 26 to 63\u00a0\u00b5M. Among them six compounds <jats:bold>4<\/jats:bold>\u2013<jats:bold>9<\/jats:bold> exhibited more potent inhibitory activity with IC<jats:sub>50<\/jats:sub> values 46.10\u2009\u00b1\u20091.16, 42.30\u2009\u00b1\u20091.18, 37.14\u2009\u00b1\u20091.21, 26.29\u2009\u00b1\u20090.76, 28.31\u2009\u00b1\u20090.64 and 31.11\u2009\u00b1\u20090.84\u00a0\u00b5M respectively, while compound <jats:bold>3<\/jats:bold> was the least active compound in the series with IC<jats:sub>50<\/jats:sub> value 63.10\u2009\u00b1\u20091.58\u00a0\u00b5M comparing with standard PEP inhibitor bacitracin (IC<jats:sub>50<\/jats:sub>\u2009=\u2009125\u2009\u00b1\u20091.50\u00a0\u00b5M). Moreover, mechanistic study was performed for the most active compounds <jats:bold>7<\/jats:bold> and <jats:bold>8<\/jats:bold> with <jats:italic>K<\/jats:italic><jats:sub><jats:italic>i<\/jats:italic><\/jats:sub> values 24.10\u2009\u00b1\u20090.0076 and 23.67\u2009\u00b1\u20090.0084\u00a0\u00b5M respectively. Further, the in silico studies suggested that the compounds exhibited potential interactions and significant molecular conformations, thereby elucidating the structural basis for their inhibitory effects.<\/jats:p>","DOI":"10.1038\/s41598-024-58428-6","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T14:01:54Z","timestamp":1711980114000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Exploring bi-carbazole-linked triazoles as inhibitors of prolyl endo peptidase via integrated in vitro and in silico study"],"prefix":"10.1038","volume":"14","author":[{"given":"Saeed","family":"Ullah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farheen","family":"Mansoor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salman Ali","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uzma","family":"Jabeen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amany I.","family":"Almars","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailah M.","family":"Almohaimeed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Basri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahad M.","family":"Alshabrmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,1]]},"reference":[{"key":"58428_CR1","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.bbapap.2011.05.011","volume":"1824","author":"VE Alvarez","year":"2012","unstructured":"Alvarez, V. 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