{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:08:46Z","timestamp":1788930526851,"version":"build-2803163510"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Lung cancer is one of the most prominent causes of cancer-related death worldwide, primarily driven by apoptosis resistance linked to the overexpression of antiapoptotic proteins. BCL-XL plays a regulatory function in cellular apoptosis, making it a critical therapeutic target in cancer treatment. In this study, we explored the potential therapeutic effects of phytocompounds isolated from leaves of Ailanthus excelsa to inhibit BCL-XL using an integrated approach combining in silico and in vitro methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Phytochemical analysis of the chloroform extract of A. excelsa leaves was performed via gas chromatography-mass spectrometry (GC-MS). Compounds were selected based on their favorable pharmacokinetic properties and subjected to molecular docking against BCL-XL, followed by molecular dynamics simulations over 100 ns, analysis of the simulation trajectory RMSF, principal component analysis, and free-energy landscape. In vitro cytotoxicity of the leaf extract was assessed by MTT assay on lung cancer cell lines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GC-MS identified 32 major bioactive compounds. Among these, decane,1,9-bis[(trimethylsilyl)oxy] and squalene were selected based on their favorable pharmacokinetic properties. Molecular docking studies revealed that both these compounds interact with the BH3-binding groove of BCL-XL through hydrophobic interactions. Further molecular dynamics simulations of decane,1,9-bis[(trimethylsilyl)oxy] and squalene over 100 ns confirmed the stability and compactness of the protein-ligand complex. The results of the simulation trajectory RMSF indicated stable structural conformations and minor fluctuations around the BH3 domain, suggesting effective binding. Principal component analysis and free-energy landscape exhibited that the binding of squalene promotes multiple conformational states, while decane,1,9-bis[(trimethylsilyl)oxy] limits flexibility in the protein conformations. In addition, the MTT assay conducted on lung cancer cell lines showed significant cytotoxicity of the A. excelsa leaf extract in a dose-dependent manner, highlighting its anticancer properties.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study emphasizes the therapeutic potential of phytocompounds as natural inhibitors of BCL-XL. The integration of GC-MS profiling, molecular docking, molecular dynamics simulations, and in vitro studies provides a comprehensive strategy for the identification of plant-derived lead molecules targeting critical cancer pathways. Further in vivo investigations and molecular validations would provide better insights into BCL-XL-targeted Phyto-therapeutics for lung cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1925157","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:42:35Z","timestamp":1788928955000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting BCL-XL-mediated apoptotic resistance in lung cancer: in silico and in vitro identification of bioactive inhibitors from Ailanthus excelsa chloroform extract"],"prefix":"10.3389","volume":"13","author":[{"given":"Abrar","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, College of Medicine, University of Ha'il","place":["Hail, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atul","family":"Kumar","sequence":"additional","affiliation":[{"name":"Medical Biotechnology Lab, Department of Biotechnology, Jamia Millia Islamia","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadaf","family":"Anwar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Medicine, University of Ha'il","place":["Hail, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halima","family":"Mustafa Elagib","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine, University of Ha\u2019il","place":["Hail, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farida","family":"Habib Khan","sequence":"additional","affiliation":[{"name":"Department of Community and Family Medicine, College of Medicine, University of Ha'il","place":["Hail, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona M.","family":"Shahien","sequence":"additional","affiliation":[{"name":"Department 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