{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T06:10:15Z","timestamp":1792822215745,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007065","name":"Nvidia","doi-asserted-by":"publisher","award":["PG153\u2010B02"],"award-info":[{"award-number":["PG153\u2010B02"]}],"id":[{"id":"10.13039\/100007065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Flavokawain A, a naturally occurring chalcone derived from\n                    <jats:italic>Piper methysticum<\/jats:italic>\n                    , has been explored for its neurotherapeutic potential. This study investigates the inhibitory activity of flavokawain A against both MAO\u2010A and MAO\u2010B isoforms using a comprehensive approach that integrates in vitro enzyme assays with in silico modelling techniques. Flavokawain A exhibited potent and selective inhibition of MAO\u2010A, with an IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 0.077\u00a0\u00b5M and a moderate selectivity index of 4.84, as compared to the clinically used reversible MAO\u2010A inhibitor toloxatone. Blood\u2013brain barrier permeability, assessed via parallel artificial membrane permeability assay, confirmed flavokawain A's central nervous system (CNS) drug\u2010likeness. Molecular docking and dynamics simulations revealed strong and stable binding of flavokawain A within the MAO\u2010A active site, supported by key hydrogen bonds and hydrophobic interactions, particularly involving Tyr444 and Lys305. Post\u2010dynamic analyses, including principal component analysis (PCA), dynamic cross\u2010correlation matrix (DCCM), and free energy landscape (FEL) mapping, indicated greater conformational adaptability and domain cooperativity in MAO\u2010A compared to MAO\u2010B. Quantum chemical (density functional theory) analysis further validated the reactivity and binding potential of flavokawain A. Collectively, these findings position flavokawain A as a promising natural, CNS\u2010permeant lead compound with selective MAO\u2010A inhibitory activity, supporting its further development for the treatment of depression and related neuropsychiatric disorders.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202501920","type":"journal-article","created":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T23:50:51Z","timestamp":1764546651000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Flavokawain A: A Natural MAO\u2010A Inhibitor With Therapeutic Promise for Depression"],"prefix":"10.1002","volume":"23","author":[{"given":"Vaishnavi","family":"Pawa","sequence":"first","affiliation":[{"name":"R.C. Patel Institute of Pharmaceutical Education &amp; Research  Near Karwand Naka Shirpur, Dhule Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Shimpi","sequence":"additional","affiliation":[{"name":"R.C. Patel Institute of Pharmaceutical Education &amp; Research  Near Karwand Naka Shirpur, Dhule Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Min","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Research Institute of Life Pharmaceutical Sciences Sunchon National University  Suncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaibhav","family":"Kadam","sequence":"additional","affiliation":[{"name":"R.C. Patel Institute of Pharmaceutical Education &amp; Research  Near Karwand Naka Shirpur, Dhule Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhatu","family":"Patil","sequence":"additional","affiliation":[{"name":"R.C. Patel Institute of Pharmaceutical Education &amp; Research  Near Karwand Naka Shirpur, Dhule Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrakant","family":"Gawli","sequence":"additional","affiliation":[{"name":"R.C. Patel Institute of Pharmaceutical Education &amp; Research  Near Karwand Naka Shirpur, Dhule Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilas","family":"Jagtap","sequence":"additional","affiliation":[{"name":"R.C. Patel Institute of Pharmaceutical Education &amp; Research  Near Karwand Naka Shirpur, Dhule Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bijo","family":"Mathew","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Amrita School of Pharmacy Amrita Vishwa Vidyapeetham  Kochi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachithra","family":"Sudevan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Amrita School of Pharmacy Amrita Vishwa Vidyapeetham  Kochi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iqrar","family":"Ansari","sequence":"additional","affiliation":[{"name":"R.C. Patel Institute of Pharmaceutical Education &amp; Research  Near Karwand Naka Shirpur, Dhule Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Research Institute of Life Pharmaceutical Sciences Sunchon National University  Suncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0920-1266","authenticated-orcid":false,"given":"Harun M.","family":"Patel","sequence":"additional","affiliation":[{"name":"R.C. Patel Institute of Pharmaceutical Education &amp; Research  Near Karwand Naka Shirpur, Dhule Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,30]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"World Health Organization \u201cDepressive disorder (depression)\u201d(2015) https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/depression."},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20194827"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27134297"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024\u20103205(02)01555\u20102"},{"key":"e_1_2_10_6_1","article-title":"Biological Activity, Hepatotoxicity, and Structure\u2010Activity Relationship of Kavalactones and Flavokavins, the Two Main Bioactive Components in Kava (Piper methysticum), Evidence\u2010Based Complement","volume":"2021","author":"Wang 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