{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T06:52:19Z","timestamp":1776927139454,"version":"3.51.2"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>This study aims to identify potential azole\u2010derived inhibitors targeting the PI3K\/AKT\/mTOR signaling pathway involved in autophagy regulation and cancer progression. A structure\u2010based virtual screening approach was employed using molecular docking, molecular dynamics (MD) simulations, and free energy calculations (MMGBSA and MMPBSA). The pharmacokinetic profiles and toxicity of lead compounds were assessed using ADMET analysis. In vitro validation was performed using MTT and MDC staining assays on MDA\u2010MB\u2010231 breast cancer cells.Among the screened compounds, KR4 demonstrated strong binding affinity towards all three kinases (\u22128.289, \u22125.222, and \u22126.331 kcal\/mol) respectively with favorable pharmacokinetic properties. MD simulation confirmed the stability of the KR4\u2010protein complexes, while post\u2010MD MMPBSA analysis validated the binding energetics. In vitro studies revealed dose\u2010dependent cytotoxicity of KR4 (IC\u2085\u2080 \u2248 39 \u00b5M) and induction of autophagy in treated cells. The integration of in silico and in vitro approaches highlights KR4 as a promising multi\u2010target inhibitor of the PI3K\/AKT\/mTOR pathway with potential anti\u2010cancer properties. These findings support further exploration of KR4 for therapeutic development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbt.70859","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T06:18:59Z","timestamp":1776925139000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational Analysis of Azole Derivatives Targeting the PI3K\/AKT\/mTOR Pathway With In Vitro Cytotoxicity and Autophagy Evaluation"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0785-7632","authenticated-orcid":false,"given":"Rathika","family":"Regurajan","sequence":"first","affiliation":[{"name":"Immuno\u2212Pharmacology Laboratory, Center for Marine Science and Technology Manonmaniam Sundaranar University Kanyakumari Dist. Tamilnadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5446-735X","authenticated-orcid":false,"given":"Merlin Sobia","family":"Poomani","sequence":"additional","affiliation":[{"name":"Genetic Engineering and Regenerative biology Lab, Department of Biotechnology Manonmaniam Sundaranar University Tirunelveli Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6811-8185","authenticated-orcid":false,"given":"Iyyadurai","family":"Mariappan","sequence":"additional","affiliation":[{"name":"Genetic Engineering and Regenerative biology Lab, Department of Biotechnology Manonmaniam Sundaranar University Tirunelveli Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4083-4467","authenticated-orcid":false,"given":"Venkatesh","family":"Subramanian","sequence":"additional","affiliation":[{"name":"Genetic Engineering and Regenerative biology Lab, Department of Biotechnology Manonmaniam Sundaranar University Tirunelveli Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0806-3271","authenticated-orcid":false,"given":"Muthumanickam","family":"Sankar","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics Alagappa University Karaikudi Tamilnadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0472-137X","authenticated-orcid":false,"given":"Boomi","family":"Pandi","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics Alagappa University Karaikudi Tamilnadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1233-6682","authenticated-orcid":false,"given":"Krishnaveni","family":"Muthan","sequence":"additional","affiliation":[{"name":"Immuno\u2212Pharmacology Laboratory, Center for Marine Science and Technology Manonmaniam Sundaranar University Kanyakumari Dist. 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