{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T07:10:55Z","timestamp":1772521855482,"version":"3.50.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"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. Bioinform."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      The traditional medicinal plant\n                      <jats:italic>Barleria buxifolia L<\/jats:italic>\n                      is well-known for its pharmacological properties. This study aims to predict the binding affinity of bioactive compounds obtained from\n                      <jats:italic>B. buxifolia<\/jats:italic>\n                      towards significant molecular targets associated with diabetes mellitus. The polyol pathway enzyme aldose reductase is associated with diabetes, making it a possible therapeutic target.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>By redocking the co-crystallised ligand sulindac sulfone into the aldose reductase binding site, the researchers proved the docking approach\u2019s reliability with a 0.117 \u00c5 root mean square deviation (RMSD). Virtual screening showed that 9-Carbomethoxy-6,11-dichloroxy-5-oxoxantho [3,2-g] tetralin (9CDOT) as a promising inhibitor, surpassing sulindac sulfone, which had a glide score of \u22129.95 kcal\/mol and binding energy of \u221255.10 kcal\/mol.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The chosen molecule exhibited significant binding affinity through \u03c0\u2013\u03c0 interactions with Trp111 and Trp219, a stabilising hydrogen bond with Leu300, and hydrophobic contacts with Val297, Ala299, and Leu300. Halogen bonding connections were found with one chlorine facing Trp219, suggesting \u03c0-halogen interaction, and the other towards Leu300 and Leu301, indicating halogen-hydrophobic stabilisation. Synergistic interactions increase ligand target site affinity and specificity. The compound was non-hepatotoxic, non-neurotoxic, and non-cytotoxic, according to the toxicity prediction. Our investigation shows that 9CDOT, a phytocompound from\n                      <jats:italic>B. buxifolia<\/jats:italic>\n                      , strongly inhibits human aldose reductase.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      The molecule is considered to be one of\n                      <jats:italic>B. buxifolia\u2019s<\/jats:italic>\n                      active antidiabetic principles, making it a promising aldose reductase inhibitor lead candidate. Further verifying its potency, an AI-assisted PCA\u2013PLS QSAR model also showed high predictive performance (R2 = 0.692), with 9CDOT showing a projected pIC\n                      <jats:sub>50<\/jats:sub>\n                      of 7.52 (IC\n                      <jats:sub>50<\/jats:sub>\n                      = 30 nM). To determine its therapeutic efficacy and investigate its potential as a lead candidate for the management of diabetes complications, more experimental validation is required.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbinf.2026.1766339","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T06:49:50Z","timestamp":1772520590000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Machine learning-based QSAR and molecular modeling of phytocompounds in Barleria buxifolia L. as a potential aldose reductase inhibitor"],"prefix":"10.3389","volume":"6","author":[{"given":"Radul R.","family":"Dev","sequence":"first","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenapoya (Deemed to be University)","place":["Mangalore, India"]}]},{"given":"Anjana C.","family":"Lalu","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenapoya (Deemed to be University)","place":["Mangalore, India"]}]},{"given":"Sinana","family":"Zarin","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenapoya (Deemed to be University)","place":["Mangalore, India"]}]},{"given":"Bristow Ben","family":"Joseph","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenapoya (Deemed to be University)","place":["Mangalore, India"]}]},{"given":"Rajesh","family":"Raju","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenapoya (Deemed to be University)","place":["Mangalore, India"]}]},{"given":"Abhithaj","family":"Jayanandan","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenapoya (Deemed to be University)","place":["Mangalore, India"]}]},{"given":"Sangeeth","family":"Thekkan","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenapoya (Deemed to be University)","place":["Mangalore, India"]}]}],"member":"1965","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"13398","DOI":"10.1038\/s41598-023-40160-2","article-title":"Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in diseases management","volume":"13","author":"Agu","year":"2023","journal-title":"Sci. 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