{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T07:35:38Z","timestamp":1774942538232,"version":"3.50.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"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                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                      remains a major global health threat due to the rising prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, which limit the effectiveness of current therapies. The \u00df-keto-acyl carrier protein synthase (KasA), a key enzyme in the FAS-II pathway for mycolic acid biosynthesis, is a promising target for new anti-tuberculosis agents.\n                      <jats:italic>Chromolaena odorata<\/jats:italic>\n                      , a medicinal plant with reported antimicrobial and antituberculosis activity, is a rich source of bioactive flavonoids, including Isosakuranetin, which shows moderate anti-tuberculosis activity. Modifications in pharmacophores\u2014such as functional groups, structural features, bond angles, and bond distances\u2014can enhance the activity of these phytochemicals and improve their potential as drug leads.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>A structure-based computational workflow was employed, including molecular docking, MM-GBSA binding energy calculations, ADMET evaluation, and 250 ns molecular dynamics simulations to investigate the binding affinity, stability, and pharmacokinetic profiles of Isosakuranetin and its derivatives against KasA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The analysis revealed differential binding affinities and dynamic stabilities of Isosakuranetin derivatives. Isn_96 exhibited the strongest binding affinity (\u22127.921 kcal\/mol), with favorable electrostatic and hydrophobic interactions involving residues HIS311, HIS345, and ASP273. Post-MDS MM-GBSA analysis confirmed its enhanced stability, displaying the highest binding free energy (\u221256.20 \u00b1 6.90 kcal\/mol). Pharmacokinetic predictions also indicated acceptable absorption and safety profiles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings suggest that Isosakuranetin derivatives, particularly Isn_96, are promising scaffolds for the design of novel KasA inhibitors. Their strong binding affinity, dynamic stability, and favorable ADMET properties highlight potential efficacy against drug-resistant M. tuberculosis. The results emphasize the potential of plant-derived flavonoids as lead compounds and underscore the value of structure-based computational approaches in guiding anti-tuberculosis drug development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbinf.2026.1777858","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T06:06:19Z","timestamp":1774937179000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting KasA: isosakuranetin derivatives as promising scaffolds for novel anti-tuberculosis agents against drug-resistant Mycobacterium tuberculosis"],"prefix":"10.3389","volume":"6","author":[{"given":"B.","family":"Angitha","sequence":"first","affiliation":[{"name":"Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University)","place":["Mangalore, Karnataka, India"]}]},{"given":"T.","family":"Amritha","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University)","place":["Mangalore, Karnataka, India"]}]},{"given":"Radul R.","family":"Dev","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University)","place":["Mangalore, Karnataka, India"]}]},{"given":"Rajesh","family":"Raju","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science, Yenepoya (Deemed to be University)","place":["Mangalore, Karnataka, India"]}]},{"given":"C. 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