{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T22:37:24Z","timestamp":1788561444279,"version":"build-2803163510"},"reference-count":63,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytochemical Analysis"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Visceral leishmaniasis (VL) is caused by <jats:italic>Leishmania donovani<\/jats:italic>. The purine and pyrimidine pathways are essential for <jats:styled-content style=\"fixed-case\"><jats:italic>L. donovani<\/jats:italic><\/jats:styled-content>. Simultaneously inhibiting multiple targets could be an effective strategy to eliminate the pathogen and treat VL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We aimed to target the essential enzymes of <jats:italic>L. donovani<\/jats:italic> and inhibit them using a multi\u2010target approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>A systematic analytical method was followed, in which first reported inhibitors of two essential enzymes (adenine phosphoribosyl\u2010transferase [APRT] and dihydroorotate dehydrogenase [DHODH]) were collected and then ADMET and PASS analyses were conducted using the Lipinski rule and Veber's rule. Additionally, molecular docking between screened ligands and proteins were performed. The stability of complexes was analyzed using molecular dynamics (MD) simulations and MMPBSA analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Initially, 6,220 unique molecules were collected from the PubChem database, and then the Lipinski rule and Veber's rule were used for screening. In total, 203 compounds passed the ADMET test; their antileishmanial properties were tested by PASS analysis. As a result, 15 ligands were identified. Molecular docking simulations between APRT or DHODH and these 15 ligands were performed. Four molecules were found to be plant\u2010derived compounds. Lig_2 and Lig_3 had good docking scores with both proteins. MD simulations were performed to determine the dynamic behavior and binding patterns of complexes. Both MD simulations and MMPBSA analysis showed Lig_3 is a promising antileishmanial inhibitor of both targets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Promising plant\u2010derived compounds that might be used to combat VL were obtained through a multi\u2010target approach.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pca.3213","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T01:13:34Z","timestamp":1675991614000},"page":"842-854","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Computational multi\u2010target approach to target essential enzymes of <i>Leishmania donovani<\/i> using comparative molecular dynamic simulations and MMPBSA analysis"],"prefix":"10.1002","volume":"34","author":[{"given":"Debanjan","family":"Saha","sequence":"first","affiliation":[{"name":"Computational Biophysics Laboratory, Department of Molecular Biology and Biotechnology Tezpur University  Tezpur Assam India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2304-2468","authenticated-orcid":false,"given":"Anupam","family":"Nath Jha","sequence":"additional","affiliation":[{"name":"Computational Biophysics Laboratory, Department of Molecular Biology and Biotechnology Tezpur University  Tezpur Assam India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"World Health Organization: Weekly Epidemiological Record (WER);2016."},{"key":"e_1_2_7_3_1","first-page":"401","article-title":"Global leishmaniasis surveillance: 2019\u20132020, a baseline for the 2030 roadmap","volume":"96","author":"Ruiz\u2010Postigo JA","year":"2021","journal-title":"Wkly Epidemiol Rec"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004349"},{"key":"e_1_2_7_5_1","unstructured":"WHO.Epidemiological situation. 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