{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:04:28Z","timestamp":1760238268411,"version":"build-2065373602"},"reference-count":60,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T00:00:00Z","timestamp":1596067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Findlay","award":["ETS Grant"],"award-info":[{"award-number":["ETS Grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Prevalence studies revealed that one-third of the human population is chronically infected with Toxoplasma gondii. Presently, such infections are without medical treatment that effectively eradicates the parasite once it is in its latent form. Moreover, the therapeutics used to treat acute infections are poorly tolerated by patients and also cause the parasite to convert into long-lasting tissue cysts. Hence, there is a dire need for compounds with antiparasitic activity against all forms of T. gondii. This study examines the antiparasitic capacity of nine novel bisphenol Z (BPZ) derivatives to determine whether they possessed any activity that prevented T. gondii replication. To begin assessing the efficacy of the novel derivatives, parasites were treated with increasing concentrations of the compounds, then doubling assays and MitoTracker staining were performed. Three of the nine compounds demonstrated strong inhibitory activity, i.e., parasite replication significantly decreased with higher concentrations. Additionally, many of the treated parasites exhibited decreases in fluorescent signaling and disruption of mitochondrial morphology. These findings suggest that bisphenol Z compounds disrupt mitochondrial function to inhibit parasite replication and may provide a foundation for the development of new and effective treatment modalities against T. gondii.<\/jats:p>","DOI":"10.3390\/microorganisms8081159","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T04:15:31Z","timestamp":1596168931000},"page":"1159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Evaluating the Antiparasitic Activity of Novel BPZ Derivatives Against Toxoplasma gondii"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2351-5571","authenticated-orcid":false,"given":"Olivia","family":"Hatton","sequence":"first","affiliation":[{"name":"Department of Biology, University of Findlay, Findlay, OH 45840, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lea","family":"Stitzlein","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Findlay, Findlay, OH 45840, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard W.","family":"Dudley","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Findlay, Findlay, OH 45840, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0822-3511","authenticated-orcid":false,"given":"Robert A.","family":"Charvat","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Findlay, Findlay, OH 45840, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1128\/iai.61.4.1169-1172.1993","article-title":"Toxoplasma gondii: A protozoan for the nineties","volume":"61","author":"Joiner","year":"1993","journal-title":"Infect. Immun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.ijpara.2009.01.005","article-title":"History of the discovery of the life cycle of Toxoplasma gondii","volume":"39","author":"Dubey","year":"2009","journal-title":"Int. J. Parasitol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/j.ijpara.2009.04.003","article-title":"Toxoplasmosis snapshots: Global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis","volume":"39","author":"Pappas","year":"2009","journal-title":"Int. J. Parasitol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"315","DOI":"10.4269\/ajtmh.1988.38.315","article-title":"Toxoplasmosis in Panama: A 10-year study","volume":"38","author":"Sousa","year":"1988","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"794","DOI":"10.4269\/ajtmh.13-0722","article-title":"Neglected parasitic infections in the United States: Toxoplasmosis","volume":"90","author":"Jones","year":"2014","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1089\/fpd.2015.2070","article-title":"A Systematic Meta-Analysis of Toxoplasma gondii Prevalence in Food Animals in the United States","volume":"13","author":"Guo","year":"2016","journal-title":"Foodborne Pathog. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1126\/science.167.3919.892","article-title":"Toxoplasma gondii: The Oocyst, Sporozoite, and Infection of Cultured Cells","volume":"167","author":"Sheffield","year":"1970","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1084\/jem.132.4.636","article-title":"The Toxoplasma Gondii Oocyst from Cat Feces","volume":"132","author":"Dubey","year":"1970","journal-title":"J. Exp. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1136\/bmj.4.5686.806-b","article-title":"Life cycle of Toxoplasma gondii","volume":"4","author":"Hutchison","year":"1969","journal-title":"BMJ"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/S0020-7519(98)00023-X","article-title":"Advances in the life cycle of Toxoplasma gondii","volume":"28","author":"Dubey","year":"1998","journal-title":"Int. J. Parasitol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Djakovi\u0107, O.D. (2012). The Life Cycle of Toxoplasma gondii in the Natural Environment. Toxoplasmosis - Recent Advances, InTechOpen.","DOI":"10.5772\/2845"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1086\/590149","article-title":"Management of Toxoplasma gondii infection during pregnancy","volume":"47","author":"Montoya","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Krueger, W.S., Hilborn, E.D., Converse, R.R., and Wade, T.J. (2014). Drinking water source and human Toxoplasma gondii infection in the United States: A cross-sectional analysis of NHANES data. BMC Public Health, 14.","DOI":"10.1186\/1471-2458-14-711"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"22551","DOI":"10.1038\/srep22551","article-title":"Prevalence, incidence estimations, and risk factors of Toxoplasma gondii infection in Germany: A representative, cross-sectional, serological study","volume":"6","author":"Wilking","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3085","DOI":"10.1080\/10408398.2017.1352563","article-title":"Toxoplasma gondii infection and food consumption: A systematic review and meta-analysis of case-controlled studies","volume":"58","author":"Belluco","year":"2018","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"78","DOI":"10.6002\/ect.2012.0303","article-title":"A rare ocular complication after a heart transplant: Toxoplasma retinitis","volume":"12","author":"Kervan","year":"2014","journal-title":"Exp. Clin. Transplant."},{"key":"ref_17","first-page":"160","article-title":"Fatal acute respiratory distress by Toxoplasma gondii in a Toxoplasma seronegative liver transplant recipient","volume":"39","author":"Miltgen","year":"2016","journal-title":"New Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"46","DOI":"10.3389\/fcimb.2019.00046","article-title":"From Entry to Early Dissemination\u2014Toxoplasma gondii\u2019s Initial Encounter with Its Host","volume":"9","author":"Betancourt","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/0002-9343(79)90271-7","article-title":"Toxoplasmosis presenting as brain abscesses. Diagnosis by computerized tomography and cytology of aspirated purulent material","volume":"67","author":"McLeod","year":"1979","journal-title":"Am. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1093\/clinids\/15.2.211","article-title":"Toxoplasmic encephalitis in AIDS","volume":"15","author":"Luft","year":"1992","journal-title":"Clin. Infect. Dis."},{"key":"ref_21","first-page":"322","article-title":"Toxoplasmosis in the non-AIDS immunocompromised host","volume":"13","author":"Israelski","year":"1993","journal-title":"Curr. Clin. Top. Infect. Dis."},{"key":"ref_22","first-page":"549","article-title":"Toxoplasma gondii infection in marrow transplant recipients: A 20 year experience","volume":"13","author":"Slavin","year":"1994","journal-title":"Bone Marrow Transplant."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/BF01690095","article-title":"Toxoplasmosis in heart transplant recipients","volume":"15","author":"Gallino","year":"1996","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1093\/clinids\/18.6.853","article-title":"Toxoplasmosis in pregnancy","volume":"18","author":"Wong","year":"1994","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1159\/000180267","article-title":"Neuropsychiatric disease and Toxoplasma gondii infection","volume":"16","author":"Henriquez","year":"2009","journal-title":"Neuroimmunomodulation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1007\/s00436-018-6040-2","article-title":"Toxoplasma gondii infection and behavioral outcomes in humans: A systematic review","volume":"117","author":"Martinez","year":"2018","journal-title":"Parasitol. Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ortiz-Guerrero, G., Gonzalez-Reyes, R.E., de-la-Torre, A., Medina-Rinc\u00f3n, G., and Nava-Mesa, M.O. (2020). Pathophysiological Mechanisms of Cognitive Impairment and Neurodegeneration by Toxoplasma gondii Infection. Brain Sci., 10.","DOI":"10.3390\/brainsci10060369"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7161","DOI":"10.1128\/AAC.02009-15","article-title":"Clinically Available Medicines Demonstrating Anti-Toxoplasma Activity","volume":"59","author":"Neville","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e20163860","DOI":"10.1542\/peds.2016-3860","article-title":"Diagnosis, Treatment, and Prevention of Congenital Toxoplasmosis in the United States","volume":"139","author":"Maldonado","year":"2017","journal-title":"Pediatrics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1056\/NEJM199212033272306","article-title":"Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome","volume":"327","author":"Porter","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1097\/01.inf.0000202070.59190.9a","article-title":"Severe sulfadiazine hypersensitivity in a child with reactivated congenital toxoplasmic chorioretinitis","volume":"25","author":"McLeod","year":"2006","journal-title":"Pediatric Infect. Dis. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"273","DOI":"10.2147\/DDDT.S60973","article-title":"Drugs in development for toxoplasmosis: Advances, challenges, and current status","volume":"11","author":"Alday","year":"2017","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1051\/parasite\/2013020","article-title":"Sulfadiazine resistance in Toxoplasma gondii: No involvement of overexpression or polymorphisms in genes of therapeutic targets and ABC transporters","volume":"20","author":"Doliwa","year":"2013","journal-title":"Parasite"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.3389\/fmicb.2018.02587","article-title":"Drug Resistance in Toxoplasma gondii","volume":"9","author":"Montazeri","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1111\/cbdd.13531","article-title":"Design, synthesis, and biological evaluation of lipophilically modified bisphenol Z derivatives","volume":"94","author":"Stitzlein","year":"2019","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Salin, N.H., Noordin, R., Al-Najjar, B.O., Kamarulzaman, E.E., Yunus, M.H., Karim, I.Z.A., Nasim, N.N.M., Zakaria, I.I., and Wahab, H.A. (2020). Identification of potential dual -targets anti- Toxoplasma gondii compounds through structure-based virtual screening and in-vitro studies. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0225232"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"559","DOI":"10.2307\/3283383","article-title":"Mutants of Toxoplasma gondii Resistant to Atovaquone (566C80) or Decoquinate","volume":"79","author":"Pfefferkorn","year":"1993","journal-title":"J. Parasitol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e01031-17","DOI":"10.1128\/AAC.01031-17","article-title":"Characterization of the Activities of Dinuclear Thiolato-Bridged Arene Ruthenium Complexes against Toxoplasma gondii","volume":"61","author":"Basto","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1645\/GE-1608.1","article-title":"Inhibition of Toxoplasma gondii and Plasmodium falciparum infections in vitro by NSC3852, a redox active antiproliferative and tumor cell differentiation agent","volume":"95","author":"Strobl","year":"2009","journal-title":"J. Parasitol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e01233-18","DOI":"10.1128\/AAC.01233-18","article-title":"Direct and Indirect Inhibition Effects of Resveratrol against Toxoplasma gondii Tachyzoites In Vitro","volume":"63","author":"Chen","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1242\/jcs.021089","article-title":"Organellar dynamics during the cell cycle of Toxoplasma gondii","volume":"121","author":"Nishi","year":"2008","journal-title":"J. Cell Sci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Garbuz, T., and Arrizabalaga, G. (2017). Lack of mitochondrial MutS homolog 1 in Toxoplasma gondii disrupts maintenance and fidelity of mitochondrial DNA and reveals metabolic plasticity. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0188040"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1006\/jsbi.2000.4228","article-title":"The Single Mitochondrion of Tachyzoites of Toxoplasma gondii","volume":"130","author":"Melo","year":"2000","journal-title":"J. Struct. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"757","DOI":"10.2307\/3276198","article-title":"Ultrastructure of trypanosoma lewisi","volume":"50","author":"Judge","year":"1964","journal-title":"J. Parasitol."},{"key":"ref_46","first-page":"97","article-title":"Electron-microscope studies on malaria parasites","volume":"4","author":"Rudzinska","year":"1959","journal-title":"Triangle"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"22997","DOI":"10.1038\/srep22997","article-title":"Oxidative stress generated during monensin treatment contributes to altered Toxoplasma gondii mitochondrial function","volume":"6","author":"Charvat","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e00229-16","DOI":"10.1128\/mSphere.00229-16","article-title":"TgPRELID, a Mitochondrial Protein Linked to Multidrug Resistance in the Parasite","volume":"2","author":"Jeffers","year":"2017","journal-title":"mSphere"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lavine, M.D., and Arrizabalaga, G. (2012). Analysis of monensin sensitivity in Toxoplasma gondii reveals autophagy as a mechanism for drug induced death. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042107"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.3390\/md10081631","article-title":"Trypanocidal action of (-)-elatol involves an oxidative stress triggered by mitochondria dysfunction","volume":"10","author":"Desoti","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/j.1365-2958.2009.06655.x","article-title":"Disruption of a mitochondrial MutS DNA repair enzyme homologue confers drug resistance in the parasite Toxoplasma gondii","volume":"72","author":"Garrison","year":"2009","journal-title":"Mol. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0166-6851(00)00184-5","article-title":"Characterization of cytochrome b from Toxoplasma gondii and Q(o) domain mutations as a mechanism of atovaquone-resistance","volume":"108","author":"McFadden","year":"2000","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3961","DOI":"10.1074\/jbc.272.7.3961","article-title":"Atovaquone, a Broad Spectrum Antiparasitic Drug, Collapses Mitochondrial Membrane Potential in a Malarial Parasite","volume":"272","author":"Srivastava","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1007\/s00018-012-1066-6","article-title":"Regulation of mitochondrial dynamics: Convergences and divergences between yeast and vertebrates","volume":"70","author":"Zhao","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e02732-19","DOI":"10.1128\/mBio.02732-19","article-title":"Identification of Fis1 interactors in Toxoplasma gondii reveals a novel protein required for peripheral distribution of the mitochondrion","volume":"11","author":"Jacobs","year":"2020","journal-title":"Mbio"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/mmi.14138","article-title":"TgDrpC, an atypical dynamin-related protein in Toxoplasma gondii, is associated with vesicular transport factors and parasite division","volume":"111","author":"Varberg","year":"2019","journal-title":"Mol. Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Melatti, C., Pieperhoff, M., Lemgruber, L., Pohl, E., Sheiner, L., and Meissner, M. (2019). A unique dynamin-related protein is essential for mitochondrial fission in Toxoplasma gondii. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007512"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"42746","DOI":"10.1038\/srep42746","article-title":"Mitochondrial behaviour throughout the lytic cycle of Toxoplasma gondii","volume":"7","author":"Ovciarikova","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_59","first-page":"110","article-title":"Electron microscopic studies on the morphology and reproduction of Toxoplasma gondii. II. Observations on the reproduction of Toxoplasma gondii (endodyogeny)","volume":"201","year":"1966","journal-title":"Zentralbl. Bakteriol. Orig."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1128\/MMBR.64.3.607-623.2000","article-title":"Lytic cycle of Toxoplasma gondii","volume":"64","author":"Black","year":"2000","journal-title":"Microbiol. Mol. Biol. Rev."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/8\/8\/1159\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:53:01Z","timestamp":1760176381000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/8\/8\/1159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,30]]},"references-count":60,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["microorganisms8081159"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms8081159","relation":{},"ISSN":["2076-2607"],"issn-type":[{"type":"electronic","value":"2076-2607"}],"subject":[],"published":{"date-parts":[[2020,7,30]]}}}