{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T15:35:56Z","timestamp":1785339356879,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Due to chronic venous insufficiency, venous leg ulcers (VLUs) develop as chronic wounds characterized by impaired healing, persistent inflammation, and endothelial dysfunction. Nitrosative stress, mitochondrial damage, and tissue apoptosis caused by excess nitric oxide (NO) produced by iNOS in macrophages and fibroblasts are contributing factors in the chronic wound environment; therefore, pharmacological modulation of iNOS presents an attractive mechanistic target in chronic wound pathophysiology. Methods: Herein, we present the use of a structure-based computational strategy to assess the inhibition of tavaborole, a boron-based antifungal agent, against iNOS using human iNOS crystal structure (PDB ID: iNOS) by molecular docking using AutoDock 4.2, 500 ns simulation of molecular dynamics (MD), with equilibration within ~50 ns and analyses over full trajectory and binding free energy calculations through the MM-PBSA approach. Results: Docking studies showed favorable binding of tavaborole (\u20136.1 kcal\/mol) in the catalytic domain, which stabilizes contacts with several key residues (CYS200, PRO350, PHE369, GLY371, TRP372, TYR373, and GLU377). MD trajectories for 1 ns showed stable structural configurations with negligible deviations (RMSD \u2248 0.44 \u00b1 0.10 nm) and hydrogen bonding, and MM-PBSA analysis confirmed energetically favorable complex formation (\u0394G_binding \u2248 18.38 \u00b1 63.24 kJ\/mol) similar to the control systems (L-arginine and 1400W). Conclusions: Taken together, these computational findings indicate that tavaborole can stably occupy the iNOS active site and interact with key catalytic residues, providing a mechanistic basis for further in vitro and ex vivo validation of its potential as an iNOS inhibitor to reduce nitrosative stress and restore endothelial homeostasis in venous leg ulcers, rather than direct therapeutic proof.<\/jats:p>","DOI":"10.3390\/ph19010137","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T15:52:57Z","timestamp":1768319577000},"page":"137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Decoding iNOS Inhibition: A Computational Voyage of Tavaborole Toward Restoring Endothelial Homeostasis in Venous Leg Ulcers"],"prefix":"10.3390","volume":"19","author":[{"given":"Naveen Kumar","family":"Velayutham","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, SRM College of Pharmacy, Kattankulathur, Chengalpattu 603 203, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chitra","family":"Vellapandian","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, SRM College of Pharmacy, Kattankulathur, Chengalpattu 603 203, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5438-9881","authenticated-orcid":false,"given":"Himanshu","family":"Paliwal","sequence":"additional","affiliation":[{"name":"Marwadi University Research Center, Faculty of Pharmacy, Marwadi University, Rajkot 360003, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5433-4562","authenticated-orcid":false,"given":"Suhaskumar","family":"Patel","sequence":"additional","affiliation":[{"name":"Formulation Research and Development, Amneal Pharmaceutical, Piscataway, NJ 08854, USA"},{"name":"Centre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhupendra G.","family":"Prajapati","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Parul Institute of Pharmacy, Faculty of Pharmacy, Parul University, Waghodia, Vadodara 391760, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3S","DOI":"10.1016\/j.jvs.2014.04.049","article-title":"Management of venous leg ulcers: Clinical practice guidelines of the Society for Vascular Surgery\u00ae and the American Venous Forum","volume":"60","author":"Passman","year":"2014","journal-title":"J. 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