{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T18:24:27Z","timestamp":1778869467672,"version":"3.51.4"},"reference-count":12,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,10,7]],"date-time":"2015-10-07T00:00:00Z","timestamp":1444176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:p>Lysine <jats:italic>\u025b<\/jats:italic>\u2010aminotransferase (<jats:styled-content style=\"fixed-case\">LAT<\/jats:styled-content>) is a protein involved in lysine catabolism, and it plays a significant role during the persistent\/latent phase of <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:styled-content style=\"fixed-case\">MTB<\/jats:styled-content>), as observed by its up\u2010regulation by ~40\u2010fold during this stage. We have used the crystal structure of <jats:styled-content style=\"fixed-case\">MTB LAT<\/jats:styled-content> in external aldimine form in complex with its substrate lysine as a template to design and identify seven lead compounds with <jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content><jats:sub>50<\/jats:sub> ranging from 18.06 to &gt; 90 <jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>. We have synthesized 21 compounds based on the identified lead, and compound <jats:bold>21<\/jats:bold> [2,2\u2032\u2010oxybis(<jats:italic>N<\/jats:italic>\u2032\u2010(4\u2010fluorobenzylidene)acetohydrazide)] was found to be the most active with <jats:styled-content style=\"fixed-case\">MTB LAT IC<\/jats:styled-content><jats:sub>50<\/jats:sub> of 0.81 \u00b1 0.03 <jats:italic>\u03bc<\/jats:italic><jats:sc>m<\/jats:sc>. Compound <jats:bold>21<\/jats:bold> also showed a 2.3 log reduction in the nutrient\u2010starved <jats:styled-content style=\"fixed-case\">MTB<\/jats:styled-content> model and was more potent than standard isoniazid and rifampicin at the same dose level of 10 <jats:italic>\u03bc<\/jats:italic>g\/mL.<\/jats:p>","DOI":"10.1111\/cbdd.12655","type":"journal-article","created":{"date-parts":[[2015,9,8]],"date-time":"2015-09-08T15:32:56Z","timestamp":1441726376000},"page":"265-274","source":"Crossref","is-referenced-by-count":9,"title":["Design and Development of <i>Mycobacterium tuberculosis<\/i> Lysine <i>\u025b<\/i>\u2010Aminotransferase Inhibitors for Latent Tuberculosis Infection"],"prefix":"10.1111","volume":"87","author":[{"given":"Brindha Devi","family":"Parthiban","sequence":"first","affiliation":[{"name":"Centre for Infectious Disease Research Department of Pharmacy Birla Institute of Technology &amp; Science\u2010Pilani Hyderabad Campus Hyderabad 500078 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shalini","family":"Saxena","sequence":"additional","affiliation":[{"name":"Centre for Infectious Disease Research Department of Pharmacy Birla Institute of Technology &amp; Science\u2010Pilani Hyderabad Campus Hyderabad 500078 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manoj","family":"Chandran","sequence":"additional","affiliation":[{"name":"Centre for Infectious Disease Research Department of Pharmacy Birla Institute of Technology &amp; Science\u2010Pilani Hyderabad Campus Hyderabad 500078 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Padma Sridevi","family":"Jonnalagadda","sequence":"additional","affiliation":[{"name":"Centre for Infectious Disease Research Department of Pharmacy Birla Institute of Technology &amp; Science\u2010Pilani Hyderabad Campus Hyderabad 500078 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renu","family":"Yadav","sequence":"additional","affiliation":[{"name":"Centre for Infectious Disease Research Department of Pharmacy Birla Institute of Technology &amp; Science\u2010Pilani Hyderabad Campus Hyderabad 500078 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudraraju Reshma","family":"Srilakshmi","sequence":"additional","affiliation":[{"name":"Centre for Infectious Disease Research Department of Pharmacy Birla Institute of Technology &amp; Science\u2010Pilani Hyderabad Campus Hyderabad 500078 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yogeeswari","family":"Perumal","sequence":"additional","affiliation":[{"name":"Centre for Infectious Disease Research Department of Pharmacy Birla Institute of Technology &amp; Science\u2010Pilani Hyderabad Campus Hyderabad 500078 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sriram","family":"Dharmarajan","sequence":"additional","affiliation":[{"name":"Centre for Infectious Disease Research Department of Pharmacy Birla Institute of Technology &amp; Science\u2010Pilani Hyderabad Campus Hyderabad 500078 India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,10,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.33073\/pjm-2012-001"},{"key":"e_1_2_6_3_1","first-page":"1374","article-title":"Age\u2010related risk of hepatotoxicity in the treatment of latent tuberculosis infection: a systematic review","volume":"14","author":"Kunst H.","year":"2010","journal-title":"Int J Tuberc Lung Dis"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152807780077282"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro749"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.2741\/1291"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.55.1.139"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.02779.x"},{"key":"e_1_2_6_9_1","first-page":"309","article-title":"Acid stress response of a mycobacterial proteome: insight from a gene ontology analysis","volume":"2","author":"Roxas B.A.","year":"2009","journal-title":"Int J Clin Exp Med"},{"key":"e_1_2_6_10_1","first-page":"105","article-title":"Mycobacterium tuberculosis response to stress from reactive oxygen and nitrogen species front","volume":"2","author":"Voskuil M.I.","year":"2011","journal-title":"Microbiology"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.08.019"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01880621"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.321"}],"container-title":["Chemical Biology &amp; 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