{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T22:22:36Z","timestamp":1778019756171,"version":"3.51.4"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["406804\/2022\u20102"],"award-info":[{"award-number":["406804\/2022\u20102"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["404236\/2021\u20109"],"award-info":[{"award-number":["404236\/2021\u20109"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["421703\/2017\u20102"],"award-info":[{"award-number":["421703\/2017\u20102"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["311949\/2019\u20103"],"award-info":[{"award-number":["311949\/2019\u20103"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["303499\/2021\u20104"],"award-info":[{"award-number":["303499\/2021\u20104"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["310888\/2022\u20100"],"award-info":[{"award-number":["310888\/2022\u20100"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005669","name":"Funda\u00e7\u00e3o de Apoio \u00e0 Pesquisa do Estado da Para\u00edba","doi-asserted-by":"publisher","award":["030\/2023"],"award-info":[{"award-number":["030\/2023"]}],"id":[{"id":"10.13039\/501100005669","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005669","name":"Funda\u00e7\u00e3o de Apoio \u00e0 Pesquisa do Estado da Para\u00edba","doi-asserted-by":"publisher","award":["300989\/2022\u20109"],"award-info":[{"award-number":["300989\/2022\u20109"]}],"id":[{"id":"10.13039\/501100005669","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017654","name":"Banco Nacional de Desenvolvimento Econ\u00f4mico e Social","doi-asserted-by":"publisher","award":["14.2.0914.1"],"award-info":[{"award-number":["14.2.0914.1"]}],"id":[{"id":"10.13039\/501100017654","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004263","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio Grande do Sul","doi-asserted-by":"publisher","award":["17\/1265\u20108"],"award-info":[{"award-number":["17\/1265\u20108"]}],"id":[{"id":"10.13039\/501100004263","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":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Tuberculosis (TB) remains a major global health threat, exacerbated by multidrug\u2010resistant\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    <\/jats:styled-content>\n                    (MTB) strains. The development of new anti\u2010TB agents is crucial. In this study, 17 isatin derivatives synthesized by our research group were evaluated for their in\u00a0vitro activity against MTB strains and the two most potent compounds were assessed for cytotoxicity. Additionally, molecular docking was performed against 22 MTB protein targets to explore possible mechanisms of action, and ADMET predictions were used to determine pharmacokinetic and pharmacodynamic suitability. Also, we investigated the activity of A15, A16, and A17 against two genetically characterized multidrug\u2010resistant clinical isolates (PT\u201012 and PT\u201020). As a result, the compounds A16 and A17 exhibited the highest anti\u2010TB activity (MIC\u2009=\u200910\u2009\u03bcM for both). Inverse molecular docking indicated the enzyme enoyl\u2010[acyl\u2010carrier\u2010protein] reductase as a potential biological target. Cytotoxicity assays confirmed that A16 and A17 were non\u2010toxic, and ADMET predictions indicated suitable drug\u2010like properties for anti\u2010TB therapy. Notably, A16 and A17 showed inhibitory effects against drug\u2010resistant MTB isolates, with minimum inhibitory concentrations (MICs) ranging from 10 to 20\u2009\u03bcM, suggesting their potential to overcome resistance mechanisms linked to mutations in katG and rpoB. These findings highlight A16 and A17 as promising candidates for anti\u2010TB agents, particularly against multidrug\u2010resistant strains.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70152","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T13:28:12Z","timestamp":1751376492000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["In Vitro and\n                    <i>In Silico<\/i>\n                    Evaluation of Isatin\u2010Derived Spirooxindoles as Antituberculosis Drug Candidates"],"prefix":"10.1111","volume":"106","author":[{"given":"Fernanda Rodrigues","family":"de Lima","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Qu\u00edmica Universidade Federal da Para\u00edba (UFPB)  Jo\u00e3o Pessoa Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6027-1759","authenticated-orcid":false,"given":"J\u00e9ssika","family":"de Oliveira Viana","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Qu\u00edmica Universidade Federal da Para\u00edba (UFPB)  Jo\u00e3o Pessoa Brazil"},{"name":"National Institute of Science and Technology on Molecular Sciences\u2010INCT\u2010CiMol  Jo\u00e3o Pessoa Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleff Cruz","family":"de Castro","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Qu\u00edmica Universidade Federal da Para\u00edba (UFPB)  Jo\u00e3o Pessoa Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo","family":"Cristiano","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Qu\u00edmica Universidade Federal da Para\u00edba (UFPB)  Jo\u00e3o Pessoa Brazil"},{"name":"National Institute of Science and Technology on Molecular Sciences\u2010INCT\u2010CiMol  Jo\u00e3o Pessoa Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcia Alberton","family":"Perell\u00f3","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Instituto Nacional de Ci\u00eancia e Tecnologia em Tuberculose (INCT\u2010TB) Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul (PUCRS)  Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexia de Matos","family":"Czeczot","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Instituto Nacional de Ci\u00eancia e Tecnologia em Tuberculose (INCT\u2010TB) Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul (PUCRS)  Porto Alegre Brazil"},{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Biologia Celular e Molecular, Escola de Ci\u00eancias da Sa\u00fade e da Vida, PUCRS  Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiano Valim","family":"Bizarro","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Instituto Nacional de Ci\u00eancia e Tecnologia em Tuberculose (INCT\u2010TB) Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul (PUCRS)  Porto Alegre Brazil"},{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Biologia Celular e Molecular, Escola de Ci\u00eancias da Sa\u00fade e da Vida, PUCRS  Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Machado","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Instituto Nacional de Ci\u00eancia e Tecnologia em Tuberculose (INCT\u2010TB) Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul (PUCRS)  Porto Alegre Brazil"},{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Biologia Celular e Molecular, Escola de Ci\u00eancias da Sa\u00fade e da Vida, PUCRS  Porto Alegre Brazil"},{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Medicina e Ci\u00eancias da Sa\u00fade, PUCRS  Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiz Augusto","family":"Basso","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF), Instituto Nacional de Ci\u00eancia e Tecnologia em Tuberculose (INCT\u2010TB) Pontif\u00edcia Universidade Cat\u00f3lica do Rio Grande do Sul (PUCRS)  Porto Alegre Brazil"},{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Biologia Celular e Molecular, Escola de Ci\u00eancias da Sa\u00fade e da Vida, PUCRS  Porto Alegre Brazil"},{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Medicina e Ci\u00eancias da Sa\u00fade, PUCRS  Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio Gabriel","family":"Lima\u2010Junior","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Qu\u00edmica Universidade Federal da Para\u00edba (UFPB)  Jo\u00e3o Pessoa Brazil"},{"name":"National Institute of Science and Technology on Molecular Sciences\u2010INCT\u2010CiMol  Jo\u00e3o Pessoa Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valn\u00eas da Silva","family":"Rodrigues\u2010Junior","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Produtos Naturais e Sint\u00e9ticos Bioativos Universidade Federal da Para\u00edba (UFPB)  Jo\u00e3o\u00a0Pessoa Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4823-5290","authenticated-orcid":false,"given":"Karen Cacilda","family":"Weber","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Qu\u00edmica Universidade Federal da Para\u00edba (UFPB)  Jo\u00e3o Pessoa Brazil"},{"name":"National Institute of Science and Technology on Molecular Sciences\u2010INCT\u2010CiMol  Jo\u00e3o Pessoa Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.4094"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.5b00044"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2012\u20100044"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.4591"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15030272"},{"key":"e_1_2_8_8_1","unstructured":"ChemAxon.2023.\u201cChemAxon Marvin 23.10.\u201dhttps:\/\/www.chemaxon.com."},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909042073"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2006.07.034"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.4213"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr374"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010024\u201000504\u20102"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26175124"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2009.129"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr777"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12635"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756\u20100500\u20107\u201015"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.3189"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1996.0897"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2013.02.006"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/minf.202000211"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201008\u20101860"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci100050v"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/10406638.2022.2138927"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2020.128900"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758\u20102946\u20103\u201033"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102164\u201015\u2010991"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20084"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00213"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon.14.290"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2021.105242"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1402584"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.21577\/1984-6835.20220075"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450118666170711150034"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr300135y"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1134\/S106816202404023X"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001721"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm049092j"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.14.4059\u20104067.2000"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci0100567"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky427"},{"key":"e_1_2_8_44_1","unstructured":"World Health Organization.2024.\u201cGlobal Tuberculosis Report 2024.\u201dhttps:\/\/www.who.int\/publications\/i\/item\/9789240101531."},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.2471\/B09403"},{"key":"e_1_2_8_46_1","first-page":"67","volume-title":"Antibi\u00f3ticos. M\u00e9todos em Biologia Molecular","author":"Yu W.","year":"2017"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201208749"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.70152","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cbdd.70152","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.70152","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T11:44:29Z","timestamp":1775994269000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.70152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1111\/cbdd.70152"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.70152","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"2025-03-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70152"}}