{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T21:11:46Z","timestamp":1789074706885,"version":"build-2803163510"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"Suppl 1","license":[{"start":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T00:00:00Z","timestamp":1454284800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,10,12]],"date-time":"2016-10-12T00:00:00Z","timestamp":1476230400000},"content-version":"vor","delay-in-days":254,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:bold>Objective\/background:<\/jats:bold>\n                      \u201cThe captain of all these men of death\u201d, is the apt sobriquet for the age-old disease tuberculosis (TB). Despite the availability of many drugs, cases of increasing resistance in the forms of multi-drug and extensively drug-resistant TB and persistence [characteristic of\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      (MTB)] make the eradication of TB a nightmare. Approval of bedaquiline by the Food and Drug Administration focused attention on quinoline scaffolds for development of new anti-TB agents. Lysine [Latin Small Letter Open E]-aminotransferase (LAT) in MTB plays a pivotal role in regulating amino acid synthesis, which in turn affects mycobacterial persistence. Here, developed quinoline inhibitors that targeted LAT with an objective to eliminate dormant forms of mycobacterium.\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:bold>Methods:<\/jats:bold>\n                      Using e-pharmacophore approaches, quinolone (PBD: 2CJD) leads were found to inhibit lysine binding to LAT. To investigate structural activity relationships, 21 analogues were synthesized and characterized based on the identified lead molecules.\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:bold>Results:<\/jats:bold>\n                      Among the derivatives, N-(pyridin-2-yl methyl)-2-(4-(quinolin-4-yl) piperazin-1-yl) acetamide was identified as a potent molecule, with an IC50 for LAT of 1.04 \u03bcM. In nutrient-starved and zebra fish models, this molecule exhibited logarithmic reductions of 2.1- and 2.2-fold, respectively, at a concentration of 10 \u03bcg\/mL. The compound also exhibited good activity against persistent forms of mycobacteria (biofilm model), showing logarithmic reduction of 2.8-fold. Additionally, the hit molecule showed concentration-dependent kill kinetics against dormant forms of mycobacteria, and were devoid of cytotoxicity against RAW cell lines 264.7 at concentrations of 50 \u03bcM.\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:bold>Conclusion:<\/jats:bold>\n                      Our results indicated that the hit molecule showed activity against both active and persistent forms of infection, which is ideal for new anti-TB agents. This molecule requires further pharmacokinetic and dynamic screening for development as new drug candidate.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.ijmyco.2016.09.006","type":"journal-article","created":{"date-parts":[[2016,10,21]],"date-time":"2016-10-21T18:45:22Z","timestamp":1477075522000},"page":"S121-S122","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Design and development of novel inhibitors for the treatment of latent tuberculosis"],"prefix":"10.4103","volume":"5","author":[{"given":"Rudraraju Srilakshmi","family":"Reshma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perumal","family":"Yogeeswari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dharmarajan","family":"Sriram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","container-title":["The International Journal of Mycobacteriology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/api.elsevier.com\/content\/article\/PII:S2212553116300887?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/api.elsevier.com\/content\/article\/PII:S2212553116300887?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ovid.com\/01929415-201605001-00075","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T21:01:24Z","timestamp":1789074084000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/01929415-201605001-00075"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2]]},"references-count":0,"journal-issue":{"issue":"Suppl 1","published-print":{"date-parts":[[2016]]}},"URL":"https:\/\/doi.org\/10.1016\/j.ijmyco.2016.09.006","relation":{},"ISSN":["2212-5531","2212-554X"],"issn-type":[{"value":"2212-5531","type":"print"},{"value":"2212-554X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2]]}}}