{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T05:39:41Z","timestamp":1775885981422,"version":"3.50.1"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T00:00:00Z","timestamp":1312156800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Drug resistance in\n            <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n            has become a serious global health threat, which is now complicated by the emergence of extensively drug-resistant strains. New drugs that are active against drug-resistant tuberculosis (TB) are needed. We chose to search for new inhibitors of the enoyl-acyl carrier protein (ACP) reductase InhA, the target of the first-line TB drug isoniazid (also known as isonicotinoic acid hydrazide [INH]). A subset of a chemical library, composed of 300 compounds inhibiting\n            <jats:italic>Plasmodium falciparum<\/jats:italic>\n            enoyl reductase, was tested against\n            <jats:italic>M. tuberculosis<\/jats:italic>\n            . Four compounds were found to inhibit\n            <jats:italic>M. tuberculosis<\/jats:italic>\n            growth with MICs ranging from 1 \u03bcM to 10 \u03bcM. Testing of these compounds against\n            <jats:italic>M. tuberculosis in vitro<\/jats:italic>\n            revealed that only two compounds (CD39 and CD117) were bactericidal against drug-susceptible and drug-resistant\n            <jats:italic>M. tuberculosis<\/jats:italic>\n            . These two compounds were also bactericidal against\n            <jats:italic>M. tuberculosis<\/jats:italic>\n            incubated under anaerobic conditions. Furthermore, CD39 and CD117 exhibited increased bactericidal activity when used in combination with INH or rifampin, but CD39 was shown to be toxic to eukaryotic cells. The compounds inhibit InhA as well the fatty acid synthase type I, and CD117 was found to also inhibit tuberculostearic acid synthesis. This study provides the TB drug development community with two chemical scaffolds that are suitable for structure-activity relationship study to improve on their cytotoxicities and bactericidal activities\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.00266-11","type":"journal-article","created":{"date-parts":[[2011,6,1]],"date-time":"2011-06-01T03:44:58Z","timestamp":1306899898000},"page":"3889-3898","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":61,"title":["Novel Inhibitors of InhA Efficiently Kill\n            <i>Mycobacterium tuberculosis<\/i>\n            under Aerobic and Anaerobic Conditions"],"prefix":"10.1128","volume":"55","author":[{"given":"Catherine","family":"Vilch\u00e8ze","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony D.","family":"Baughn","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JoAnn","family":"Tufariello","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence W.","family":"Leung","sequence":"additional","affiliation":[{"name":"Mount Sinai School of Medicine, Department of Microbiology, 1 Gustave L. Levy Place, New York, New York 10029"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mack","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Texas A&amp;M University, College Station, Texas 77843"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher F.","family":"Basler","sequence":"additional","affiliation":[{"name":"Mount Sinai School of Medicine, Department of Microbiology, 1 Gustave L. Levy Place, New York, New York 10029"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Alland","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine and the Ruy V. Louren\u00e7o Center for the Study of Emerging and Re-emerging Pathogens, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James C.","family":"Sacchettini","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Texas A&amp;M University, College Station, Texas 77843"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel S.","family":"Freundlich","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Texas A&amp;M University, College Station, Texas 77843"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"William R.","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1106753"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.2.183"},{"key":"e_1_3_2_4_2","first-page":"1766","article-title":"Utility of the enaminonitrile moiety in the synthesis of some biologically active thienopyrimidine derivatives. 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