{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T03:47:35Z","timestamp":1768276055685,"version":"3.49.0"},"reference-count":53,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,2,26]],"date-time":"2022-02-26T00:00:00Z","timestamp":1645833600000},"content-version":"am","delay-in-days":347,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Several rationally designed isoniazid (INH), pyrazinamide (PZA) and ciprofloxacin (CPF) derivatives were conveniently synthesized and evaluated in vitro against H37Rv <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>M. tb<\/jats:italic>) strain. CPF derivative <jats:bold>16<\/jats:bold> displayed a modest activity (MIC\u00a0=\u00a016\u00a0\u00b5g\/ml) and was docked into the <jats:italic>M. tb<\/jats:italic> DNA gyrase. Isoniazid\u2010pyrazinoic acid (INH\u2010POA) hybrid <jats:bold>21a<\/jats:bold> showed the highest potency in our study (MIC\u00a0=\u00a02\u00a0\u00b5g\/ml). It also retained its high activity against the other tested <jats:italic>M. tb<\/jats:italic> drug\u2010sensitive strain (DS) V4207 (MIC\u00a0=\u00a04\u00a0\u00b5g\/ml) and demonstrated negligible cytotoxicity against Vero cells (IC<jats:sub>50<\/jats:sub>\u00a0\u2265\u00a064\u00a0\u00b5g\/ml). Four tested drug\u2010resistant (DR) <jats:italic>M. tb<\/jats:italic> strains were refractory to <jats:bold>21a<\/jats:bold>, similar to INH, whilst being sensitive to CPF. Compound <jats:bold>21a<\/jats:bold> was also inactive against two non\u2010tuberculous mycobacterial (NTM) strains, suggesting its selective activity against <jats:italic>M. tb<\/jats:italic>. The noteworthy activity of <jats:bold>21a<\/jats:bold> against DS strains and its low cytotoxicity highlight its potential to treat DS <jats:italic>M. tb<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/cbdd.13836","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T04:40:34Z","timestamp":1614400834000},"page":"1137-1150","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Facile synthesis and antimycobacterial activity of isoniazid, pyrazinamide and ciprofloxacin derivatives"],"prefix":"10.1111","volume":"97","author":[{"given":"Shahinda S. R.","family":"Alsayed","sequence":"first","affiliation":[{"name":"School of Pharmacy and Biomedical Sciences Faculty of Health Sciences Curtin University Perth WA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shichun","family":"Lun","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease Department of Medicine Center for Tuberculosis Research Johns Hopkins School of Medicine Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Payne","sequence":"additional","affiliation":[{"name":"School of Molecular and Life Sciences Curtin University Perth WA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William R.","family":"Bishai","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease Department of Medicine Center for Tuberculosis Research Johns Hopkins School of Medicine Baltimore MD USA"},{"name":"Howard Hughes Medical Institute Chevy Chase MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hendra","family":"Gunosewoyo","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomedical Sciences Faculty of Health Sciences Curtin University Perth WA Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,3,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525055113"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi500682e"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt124"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874467211666181025141114"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9RA10663D"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo501380y"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2011.05.115"},{"issue":"1","key":"e_1_2_8_9_1","first-page":"E9","article-title":"The history of tuberculosis: From the first historical records to the isolation of Koch's bacillus","volume":"58","author":"Barberis I.","year":"2017","journal-title":"Journal of Preventive Medicine and Hygiene"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525047113"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.12.14"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.5.1004"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(14)70031-1"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2019.04.012"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2019.10.005"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.34.3.496"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/ml400306r"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2017.03.028"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.04.002"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.2174\/157340613804488404"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/resp.13304"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2011.01.047"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3907"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01367"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr566"},{"issue":"2","key":"e_1_2_8_26_1","first-page":"155","article-title":"Pyrazinoic acid hydrazide derivatives: Synthesis and antimycobacterial activities","volume":"9","author":"Miniyar P.","year":"1999","journal-title":"Indian Journal of Heterocyclic Chemistry"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01819-14"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol402200x"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.advms.2015.09.007"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm4003878"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2016.03.062"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9RA03380G"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002464"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2015.52"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201000490"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201308-1446ED"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1134\/S107042801804019X"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a017863"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/2049-632X.12108"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2014.04.006"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b00415"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm301721e"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2016.10.026"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.7b00196"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2016.09.004"},{"issue":"4","key":"e_1_2_8_46_1","first-page":"307","article-title":"The totally drug resistant tuberculosis (TDR\u2010TB)","volume":"6","author":"Velayati A. A.","year":"2013","journal-title":"International Journal of Clinical and Experimental Medicine"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp4123425"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.02.016"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr100264t"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05894-11"},{"key":"e_1_2_8_51_1","volume-title":"World Health Organisation Global Tuberculosis Report, Geneva","author":"WHO","year":"2020"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1892"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1700062114"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-51-1-42"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.13836","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cbdd.13836","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/am-pdf\/10.1111\/cbdd.13836","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.13836","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T04:48:02Z","timestamp":1693543682000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.13836"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,16]]},"references-count":53,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1111\/cbdd.13836"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.13836","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,16]]},"assertion":[{"value":"2020-11-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}