{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T06:28:15Z","timestamp":1762064895911,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T00:00:00Z","timestamp":1661904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["270650915\/GRK 2158","K138672","FK134653"],"award-info":[{"award-number":["270650915\/GRK 2158","K138672","FK134653"]}]},{"name":"National Research, Development and Innovation Office","award":["270650915\/GRK 2158","K138672","FK134653"],"award-info":[{"award-number":["270650915\/GRK 2158","K138672","FK134653"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Toxoplasma gondii is an apicomplexan pathogen able to infect a wide range of warm-blooded animals, including humans, leading to toxoplasmosis. Current treatments for toxoplasmosis are associated with severe side-effects and a lack efficacy to eradicate chronic infection. Thus, there is an urgent need for developing novel, highly efficient agents against toxoplasmosis with low toxicity. For decades, natural products have been a useful source of novel bioactive compounds for the treatment of infectious pathogens. In the present study, we isolated eight natural products from the crude extract of the endophytic fungus Paraboeremia selaginellae obtained from the leaves of the plant Philodendron monstera. The natural products were tested for inhibiting Toxoplasma gondii proliferation, and their cytotoxicity was evaluated in different human cell lines. Six natural products showed antitoxoplasma activity with low or no cytotoxicity in human cell lines. Together, these findings indicate that biphenyl ethers, bioxanthracenes, and 5S,6S-phomalactone from P. selaginellae are potential candidates for novel anti-toxoplasma drugs.<\/jats:p>","DOI":"10.3390\/antibiotics11091176","type":"journal-article","created":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T23:53:21Z","timestamp":1661990001000},"page":"1176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["In Vitro Biological Activity of Natural Products from the Endophytic Fungus Paraboeremia selaginellae against Toxoplasma gondii"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1429-230X","authenticated-orcid":false,"given":"Flaminia","family":"Mazzone","sequence":"first","affiliation":[{"name":"Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University, 40225 Duesseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3267-0706","authenticated-orcid":false,"given":"Viktor E.","family":"Simons","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Biology and Biotechnology, Heinrich Heine University, 40225 Duesseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3879-4136","authenticated-orcid":false,"given":"Lasse","family":"van Geelen","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Biology and Biotechnology, Heinrich Heine University, 40225 Duesseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3190-9076","authenticated-orcid":false,"given":"Marian","family":"Frank","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Biology and Biotechnology, Heinrich Heine University, 40225 Duesseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7867-7084","authenticated-orcid":false,"given":"Attila","family":"M\u00e1ndi","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, University of Debrecen, 4002 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8831-8499","authenticated-orcid":false,"given":"Tibor","family":"Kurt\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, University of Debrecen, 4002 Debrecen, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5652-6330","authenticated-orcid":false,"given":"Klaus","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University, 40225 Duesseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3378-2067","authenticated-orcid":false,"given":"Rainer","family":"Kalscheuer","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Biology and Biotechnology, Heinrich Heine University, 40225 Duesseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"852591","DOI":"10.1155\/2012\/852591","article-title":"Comparison of protective immune responses to apicomplexan parasites","volume":"2012","author":"Frolich","year":"2012","journal-title":"J. Parasitol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.ijpara.2003.12.009","article-title":"Toxoplasma gondii: The model apicomplexan","volume":"34","author":"Kim","year":"2004","journal-title":"Int. J. Parasitol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"(2009). Toxoplasmosis of Animals and Man. By J.P. Dubey and C. P. Beattie. 220 pages. ISBN 0 8493 4618 5. CRC Press, Boca Raton, 1988. \u00a3108.00. Parasitology, 100, 500\u2013501.","DOI":"10.1017\/S0031182000078914"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Dubey, J.P. (2016). Toxoplasmosis of Animals and Humans, CRC Press.","DOI":"10.1201\/9781420092370"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"805","DOI":"10.3109\/00365548.2012.693197","article-title":"A review on human toxoplasmosis","volume":"44","author":"Saadatnia","year":"2012","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1186\/s13071-021-04769-4","article-title":"Outbreaks of clinical toxoplasmosis in humans: Five decades of personal experience, perspectives and lessons learned","volume":"14","author":"Dubey","year":"2021","journal-title":"Parasites Vectors"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"281","DOI":"10.4103\/0974-777X.83536","article-title":"Toxoplasmosis: A global threat","volume":"3","author":"Furtado","year":"2011","journal-title":"J. Glob. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/BF02306487","article-title":"Ocular toxoplasmosis; common and rare symptoms and signs","volume":"13","year":"1989","journal-title":"Int. Ophthalmol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1086\/595793","article-title":"Congenital toxoplasmosis and reinfection during pregnancy: Case report, strain characterization, experimental model of reinfection, and review","volume":"199","author":"Ajzenberg","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e00057-17","DOI":"10.1128\/CMR.00057-17","article-title":"Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice","volume":"31","author":"Dunay","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"303","DOI":"10.2174\/187152610791591593","article-title":"Comparative analysis of stage specific gene regulation of apicomplexan parasites: Plasmodium falciparum and Toxoplasma gondii","volume":"10","author":"Gopalakrishnan","year":"2010","journal-title":"Infect. Disord. Drug Targets"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural Products as Sources of New Drugs over the Nearly Four Decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s11686-020-00300-4","article-title":"The Experimental Role of Medicinal Plants in Treatment of Toxoplasma gondii Infection: A Systematic Review","volume":"66","author":"Cheraghipour","year":"2021","journal-title":"Acta Parasitol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5791","DOI":"10.1007\/s00253-018-9048-8","article-title":"Medicinal fungi: A source of antiparasitic secondary metabolites","volume":"102","author":"Lenzi","year":"2018","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/S0031-9422(97)01023-6","article-title":"Phytotoxicity of three lactones from Nigrospora sacchari","volume":"48","author":"Fukushima","year":"1998","journal-title":"Phytochemistry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1016\/S0040-4039(01)88013-8","article-title":"Two new metabolites from an unidentified nigrospora species","volume":"10","author":"Evans","year":"1969","journal-title":"Tetrahedron Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e2100493","DOI":"10.1002\/cbdv.202100493","article-title":"Computer-Guided Trypanocidal Activity of Natural Lactones Produced by Endophytic Fungus of Euphorbia umbellata","volume":"18","author":"Gusmao","year":"2021","journal-title":"Chem. Biodivers"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/S1995-7645(14)60119-X","article-title":"Antimicrobial chemical constituents from endophytic fungus Phoma sp.","volume":"7","author":"Hussain","year":"2014","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1002\/1526-4998(200012)56:12<1098::AID-PS244>3.0.CO;2-H","article-title":"A nematicidal metabolite from Verticillium chlamydosporium","volume":"56","author":"Khambay","year":"2000","journal-title":"Pest Manag. Sci. Former. Pestic. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1007\/s10886-015-0602-x","article-title":"Phomalactone from a Phytopathogenic Fungus Infecting ZINNIA elegans (ASTERACEAE) Leaves","volume":"41","author":"Meepagala","year":"2015","journal-title":"J. Chem. Ecol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.phytochem.2009.01.008","article-title":"Pyrone derivatives from the marine-derived fungus Nigrospora sp. PSU-F18","volume":"70","author":"Trisuwan","year":"2009","journal-title":"Phytochemistry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/cbdv.200700421","article-title":"Two new solanapyrone analogues from the endophytic fungus Nigrospora sp. YB-141 of Azadirachta indica","volume":"6","author":"Wu","year":"2009","journal-title":"Chem. Biodivers"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1039\/C9NP00002J","article-title":"Applications of OR\/ECD\/VCD to the structure elucidation of natural products","volume":"36","author":"Mandi","year":"2019","journal-title":"Nat. Prod. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Szabo, Z., Paczal, A., Kovacs, T., Mandi, A., Kotschy, A., and Kurtan, T. (2022). Synthesis and Vibrational Circular Dichroism Analysis of N-Heterocyclic Carbene Precursors Containing Remote Chirality Centers. Int. J. Mol. Sci, 23.","DOI":"10.3390\/ijms23073471"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","article-title":"Natural products in drug discovery: Advances and opportunities","volume":"20","author":"Atanasov","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9630","DOI":"10.1021\/acs.jafc.9b02173","article-title":"Synthesis and Biological Evaluation of (+)-Usnic Acid Derivatives as Potential Anti-Toxoplasma gondii Agents","volume":"67","author":"Guo","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1080\/13880200802215859","article-title":"Activity against Plasmodium falciparum of Lactones Isolated from the Endophytic Fungus Xylaria sp.","volume":"46","author":"Arnold","year":"2008","journal-title":"Pharm. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/28970","article-title":"Triclosan targets lipid synthesis","volume":"394","author":"McMurry","year":"1998","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0020-7519(01)00111-4","article-title":"Triclosan inhibits the growth of Plasmodium falciparum and Toxoplasma gondii by inhibition of apicomplexan Fab I","volume":"31","author":"McLeod","year":"2001","journal-title":"Int. J. Parasitol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6287","DOI":"10.1021\/jm9017724","article-title":"Identification and development of novel inhibitors of Toxoplasma gondii enoyl reductase","volume":"53","author":"Tipparaju","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.7164\/antibiotics.45.1047","article-title":"ES-242-2, -3, -4, -5, -6, -7, and -8, novel bioxanthracenes produced by Verticillium sp., which act on the N-methyl-D-aspartate receptor","volume":"45","author":"Toki","year":"1992","journal-title":"J. Antibiot."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"29","DOI":"10.7164\/antibiotics.54.29","article-title":"Bioxanthracenes from the insect pathogenic fungus. Cordyceps pseudomilitaris BCC 1620. I. Taxonomy, fermentation, isolation and antimalarial activity","volume":"54","author":"Jaturapat","year":"2001","journal-title":"J. Antibiot."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2520\/myco.53.11","article-title":"Antifungal activity of pyranone and furanone derivatives, isolated from Aspergillus sp. IFM51759, against Aspergillus fumigatus","volume":"53","author":"Komai","year":"2003","journal-title":"MYCOTOXINS-TOKYO-"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/BF02064437","article-title":"Identification of the antibiotic phomalactone from the entomopathogenic fungusHirsutella thompsonii var. synnematosa","volume":"20","author":"Krasnoff","year":"1994","journal-title":"J. Chem. Ecol."},{"key":"ref_35","first-page":"605","article-title":"6-Allyl-5, 6-dihydro-5-hydroxypyran-2-one, a lactone produced by a new Drechslera species: Specified 1H and 13C NMR assignments, mutagenic and immunomodulating testings","volume":"49","author":"Krivobok","year":"1994","journal-title":"Die Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kumarihamy, M., Ferreira, D., Croom, E.M., Sahu, R., Tekwani, B.L., Duke, S.O., Khan, S., Techen, N., and Nanayakkara, N.P.D. (2019). Antiplasmodial and Cytotoxic Cytochalasins from an Endophytic Fungus, Nemania sp. UM10M, Isolated from a Diseased Torreya taxifolia Leaf. Molecules, 24.","DOI":"10.3390\/molecules24040777"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"115151","DOI":"10.1016\/j.bmc.2019.115151","article-title":"The plant-derived chalcone Xanthoangelol targets the membrane of Gram-positive bacteria","volume":"27","author":"Meier","year":"2019","journal-title":"Bioorg Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/j.1550-7408.1977.tb04774.x","article-title":"Specific Labeling of Intracellular Toxoplasma gondii with Uracil","volume":"24","author":"Pfefferkorn","year":"1977","journal-title":"J. Protozool."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/0006-291X(86)90008-2","article-title":"Staurosporine, a potent inhibitor of phospholipid\/Ca++dependent protein kinase","volume":"135","author":"Tamaoki","year":"1986","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1021\/acsinfecdis.7b00055","article-title":"Chlorflavonin Targets Acetohydroxyacid Synthase Catalytic Subunit IlvB1 for Synergistic Killing of Mycobacterium tuberculosis","volume":"4","author":"Rehberg","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"ref_42","unstructured":"(2022, July 31). MacroModel; Schr\u00f6dinger LLC. Available online: http:\/\/www.schrodinger.com\/MacroModel."},{"key":"ref_43","unstructured":"Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, V., Barone, G., Mennucci, B., and Petersson, G.A. (2013). Gaussian 09 (Revision E.01), Gaussian, Inc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/chir.20733","article-title":"ECD cotton effect approximated by the Gaussian curve and other methods","volume":"22","author":"Stephens","year":"2009","journal-title":"Chirality"},{"key":"ref_45","unstructured":"Varetto, U. (2009). Molekel 5.4, Swiss National Supercomputing Centre."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/9\/1176\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:20:44Z","timestamp":1760142044000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/11\/9\/1176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,31]]},"references-count":45,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["antibiotics11091176"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics11091176","relation":{},"ISSN":["2079-6382"],"issn-type":[{"type":"electronic","value":"2079-6382"}],"subject":[],"published":{"date-parts":[[2022,8,31]]}}}