{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T07:59:10Z","timestamp":1781164750018,"version":"3.54.1"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":161,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Microbiology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aim<\/jats:title>\n                    <jats:p>\n                      Tuberculosis (TB) is caused by\n                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                      (\n                      <jats:italic>Mtb<\/jats:italic>\n                      ) and is the leading cause of death from a single bacterium. In addition, the increasing incidence of multidrug\u2010resistant tuberculosis (MDR\u2010TB) has led to the research of new compounds that are effective against Mtb. Therefore, in this study we evaluated the in vitro cytotoxicity and activity of two neolignans\u2014conocarpan (1) and eupomatenoid\u20106 (2)\u2014isolated from\n                      <jats:italic>Piper solmsianum<\/jats:italic>\n                      , against drug\u2010susceptible and multidrug\u2010resistant (MDR\u2010TB)\n                      <jats:italic>Mtb<\/jats:italic>\n                      isolates, as well as other bacteria.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Procedure<\/jats:title>\n                    <jats:p>\n                      Compounds were obtained through high\u2010performance liquid chromatography. The in vitro activities were determined by the resazurin microtiter assay, and their combinatory effect with anti\u2010TB and antiretroviral were determined by the resazurin drug combination microtiter assay against\n                      <jats:italic>Mtb<\/jats:italic>\n                      H37Rv and 14 clinical isolates (including 10 MDR\u2010TB). The cytotoxicity was evaluated in J774.A1, HeLa, VERO, and MRC\u20105 cells by MTT assay. The analysis of the absorption, distribution, metabolism, and excretion of neolignans was performed on Swiss ADME.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Compounds (1) and (2) showed activity against\n                      <jats:italic>Mtb<\/jats:italic>\n                      H37Rv, 14 Mtb clinical isolates,\n                      <jats:italic>Mycobacterium abscessus<\/jats:italic>\n                      , and\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      , with the minimum inhibitory concentrations ranging from 3.90 to 125\u2009\n                      <jats:italic>\u03bc<\/jats:italic>\n                      g\/mL. Only (1) exhibited synergism with rifampicin, and none of them presented an antagonistic effect. Both substances were more selective against bacteria, and (2) was the least cytotoxic. The (1) and (2) have high gastrointestinal permeability and do not violate the Lipinski rules.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>The synergistic interaction between conocarpan and rifampicin, coupled with the lack of antagonism with antiretroviral drugs, suggests that these neolignans are promising candidates for further development in the treatment of drug\u2010resistant TB and TB\/HIV coinfection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/ijm\/9147877","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T07:18:14Z","timestamp":1781162294000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Conocarpan and Eupomatenoid\u20106 as Natural Prototypes for Antituberculosis Compounds"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8445-0743","authenticated-orcid":false,"given":"Lincoln Lu\u00eds","family":"Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9863-018X","authenticated-orcid":false,"given":"Anderson Valdiney Gomes","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5824-8573","authenticated-orcid":false,"given":"Debora Cristina","family":"Baldoqui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathally Claudiane","family":"de Souza Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7973-4098","authenticated-orcid":false,"given":"Vera Lucia Dias","family":"Siqueira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0345-1600","authenticated-orcid":false,"given":"Katiany Rizzieri","family":"Caleffi-Ferracioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6228-4780","authenticated-orcid":false,"given":"Rosilene Fressatti","family":"Cardoso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6734-9520","authenticated-orcid":false,"given":"Rosi Zanoni","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9129-2445","authenticated-orcid":false,"given":"Regiane Bertin","family":"de Lima Scodro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"e_1_2_10_1_2","volume-title":"Global Tuberculosis Report 2023","author":"World Health Organization","year":"2023"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.01.026"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2016.11.015"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1026"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.04.002"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2019.112255"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24071364"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2013.10.011"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2013.01.005"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11418-010-0421-x"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.28.1527"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1515\/znc-2007-3-404"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0103-50532012005000077"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762003000800025"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2006.02.029"},{"key":"e_1_2_10_16_2","volume-title":"CLSI Standard M24-A2","author":"Woods G. 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