{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T12:43:55Z","timestamp":1765889035729,"version":"build-2065373602"},"reference-count":54,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre, Poland","award":["2018\/31\/N\/NZ6\/03004","B1711000000263.01","DS15"],"award-info":[{"award-number":["2018\/31\/N\/NZ6\/03004","B1711000000263.01","DS15"]}]},{"name":"Faculty of Biology and Environmental Protection, University of Lodz","award":["2018\/31\/N\/NZ6\/03004","B1711000000263.01","DS15"],"award-info":[{"award-number":["2018\/31\/N\/NZ6\/03004","B1711000000263.01","DS15"]}]},{"name":"Medical University of Lublin","award":["2018\/31\/N\/NZ6\/03004","B1711000000263.01","DS15"],"award-info":[{"award-number":["2018\/31\/N\/NZ6\/03004","B1711000000263.01","DS15"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Two distinct intracellular pathogens, namely Mycobacterium tuberculosis (Mtb) and Toxoplasma gondii (Tg), cause major public health problems worldwide. In addition, serious and challenging health problems of co-infections of Tg with Mtb have been recorded, especially in developing countries. Due to this fact, as well as the frequent cases of resistance to the current drugs, novel anti-infectious therapeutics, especially those with dual (anti-Tg and anti-Mtb) modes of action, are needed. To address this issue, we explored the anti-Tg potential of thiazolidinedione-based (TZD-based) hybrid molecules with proven anti-Mtb potency. Several TZD hybrids with pyridine-4-carbohydrazone (PCH) or thiosemicarbazone (TSC) structural scaffolds were more effective and more selective than sulfadiazine (SDZ) and trimethoprim (TRI). Furthermore, all of these molecules were more selective than pyrimethamine (PYR). Further studies for the most potent TZD-TSC hybrids 7, 8 and 10 and TZD-PCH hybrid molecule 2 proved that these compounds are non-cytotoxic, non-genotoxic and non-hemolytic. Moreover, they could cross the blood\u2013brain barrier (BBB), which is a critical factor linked with ideal anti-Tg drug development. Finally, since a possible link between Tg infection and the risk of glioblastoma has recently been reported, the cytotoxic potential of TZD hybrids against human glioblastoma cells was also evaluated. TZD-PCH hybrid molecule 2 was found to be the most effective, with an IC50 of 19.36 \u00b1 1.13 \u00b5g\/mL against T98G cells.<\/jats:p>","DOI":"10.3390\/ijms24032069","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T06:52:41Z","timestamp":1674197561000},"page":"2069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["TZD-Based Hybrid Molecules Act as Dual Anti-Mycobacterium tuberculosis and Anti-Toxoplasma gondii Agents"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3265-0409","authenticated-orcid":false,"given":"Katarzyna","family":"Dzitko","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7520-3238","authenticated-orcid":false,"given":"Barbara","family":"Kapro\u0144","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Medical University of Lublin, 20-080 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8198-7702","authenticated-orcid":false,"given":"Agata","family":"Paneth","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4980-1074","authenticated-orcid":false,"given":"Adrian","family":"Bekier","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8162-8435","authenticated-orcid":false,"given":"Tomasz","family":"Plech","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical University of Lublin, 20-080 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3091-8387","authenticated-orcid":false,"given":"Piotr","family":"Paneth","sequence":"additional","affiliation":[{"name":"Institute of Applied Radiation Chemistry, Faculty of Chemistry, Lodz University of Technology, 90-924 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8817-7470","authenticated-orcid":false,"given":"Nazar","family":"Trotsko","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.3389\/fcimb.2017.00347","article-title":"Purinergic signaling: A common path in the macrophage response against Mycobacterium tuberculosis and Toxoplasma gondii","volume":"7","author":"Tailleux","year":"2017","journal-title":"Front. 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