{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:11:20Z","timestamp":1790856680486,"version":"4.1.0"},"reference-count":72,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Economy","award":["SAF2016-76080-R"],"award-info":[{"award-number":["SAF2016-76080-R"]}]},{"name":"Spanish Ministry of Science &amp; Innovation","award":["PID2019-110810RB-I00"],"award-info":[{"award-number":["PID2019-110810RB-I00"]}]},{"name":"Generalitat of Catalonia Universities and Research Department","award":["2017SGR00924"],"award-info":[{"award-number":["2017SGR00924"]}]},{"name":"Carlos III Health Institute (ISCIII) RICET Network for Cooperative Research in Tropical Diseases","award":["RD12\/0018\/0010 and FEDER"],"award-info":[{"award-number":["RD12\/0018\/0010 and FEDER"]}]},{"DOI":"10.13039\/501100004587","name":"ISCIII","doi-asserted-by":"publisher","award":["PI18\/01054"],"award-info":[{"award-number":["PI18\/01054"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Generalitat of Catalonia Department of Health","award":["PERIS 2016\u20132010 SLT008\/18\/00132"],"award-info":[{"award-number":["PERIS 2016\u20132010 SLT008\/18\/00132"]}]},{"name":"Spanish Ministry of Education, Culture and Sports","award":["FPU grant ref. 14\/00818"],"award-info":[{"award-number":["FPU grant ref. 14\/00818"]}]},{"name":"the Spanish Ministry of Science, Innovation and Universities","award":["\u201cCentro de Excelencia Severo Ochoa 2019\u20132023\u201d Program (CEX2018-000806-S)"],"award-info":[{"award-number":["\u201cCentro de Excelencia Severo Ochoa 2019\u20132023\u201d Program (CEX2018-000806-S)"]}]},{"name":"Generalitat of Catalonia","award":["\u201cCERCA Program\u201d"],"award-info":[{"award-number":["\u201cCERCA Program\u201d"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Malaria and Chagas disease, caused by Plasmodium spp. and Trypanosoma cruzi parasites, remain important global health problems. Available treatments for those diseases present several limitations, such as lack of efficacy, toxic side effects, and drug resistance. Thus, new drugs are urgently needed. The discovery of new drugs may be benefited by considering the significant biological differences between hosts and parasites. One of the most striking differences is found in the purine metabolism, because most of the parasites are incapable of de novo purine biosynthesis. Herein, we have analyzed the in vitro anti-P. falciparum and anti-T. cruzi activity of a collection of 81 purine derivatives and pyrimidine analogs. We firstly used a primary screening at three fixed concentrations (100, 10, and 1 \u00b5M) and progressed those compounds that kept the growth of the parasites &lt; 30% at 100 \u00b5M to dose\u2013response assays. Then, we performed two different cytotoxicity assays on Vero cells and human HepG2 cells. Finally, compounds specifically active against T. cruzi were tested against intracellular amastigote forms. Purines 33 (IC50 = 19.19 \u00b5M) and 76 (IC50 = 18.27 \u00b5M) were the most potent against P. falciparum. On the other hand, 6D (IC50 = 3.78 \u00b5M) and 34 (IC50 = 4.24 \u00b5M) were identified as hit purines against T. cruzi amastigotes. Moreover, an in silico docking study revealed that P. falciparum and T. cruzi hypoxanthine guanine phosphoribosyltransferase enzymes could be the potential targets of those compounds. Our study identified two novel, purine-based chemotypes that could be further optimized to generate potent and diversified anti-parasitic drugs against both parasites.<\/jats:p>","DOI":"10.3390\/ph14070638","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T05:00:10Z","timestamp":1625115610000},"page":"638","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Novel Purine Chemotypes with Activity against Plasmodium falciparum and Trypanosoma cruzi"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7107-5374","authenticated-orcid":false,"given":"Nieves","family":"Martinez-Peinado","sequence":"first","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), Hospital Cl\u00ednic\u2014University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9510-714X","authenticated-orcid":false,"given":"\u00c1lvaro","family":"Lorente-Mac\u00edas","sequence":"additional","affiliation":[{"name":"Department of Medicinal & Organic Chemistry and Excellence Research Unit of \u201cChemistry Applied to Biomedicine and the Environment\u201d, Faculty of Pharmacy, University of Granada, Campus de Cartuja s\/n, 18071 Granada, Spain"},{"name":"Institute of Biopathology and Regenerative Medicine, Centre for Biomedical Research, University of Granada, Avda. del Conocimiento s\/n, 18100 Granada, Spain"},{"name":"Cancer Research UK Edinburgh Centre, Institute of Genetics & Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Garc\u00eda-Salguero","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), Hospital Cl\u00ednic\u2014University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5396-3757","authenticated-orcid":false,"given":"Nuria","family":"Cortes-Serra","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), Hospital Cl\u00ednic\u2014University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel","family":"Fenollar-Collado","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), Hospital Cl\u00ednic\u2014University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1003-5376","authenticated-orcid":false,"given":"Albert","family":"Ros-Lucas","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), Hospital Cl\u00ednic\u2014University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquim","family":"Gascon","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), Hospital Cl\u00ednic\u2014University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4237-1075","authenticated-orcid":false,"given":"Maria-Jesus","family":"Pinazo","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), Hospital Cl\u00ednic\u2014University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio J.","family":"Molina","sequence":"additional","affiliation":[{"name":"Institute of Biopathology and Regenerative Medicine, Centre for Biomedical Research, University of Granada, Avda. del Conocimiento s\/n, 18100 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1029-2855","authenticated-orcid":false,"given":"Asier","family":"Unciti-Broceta","sequence":"additional","affiliation":[{"name":"Cancer Research UK Edinburgh Centre, Institute of Genetics & Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J.","family":"D\u00edaz-Moch\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Medicinal & Organic Chemistry and Excellence Research Unit of \u201cChemistry Applied to Biomedicine and the Environment\u201d, Faculty of Pharmacy, University of Granada, Campus de Cartuja s\/n, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0617-6408","authenticated-orcid":false,"given":"Mar\u00eda J.","family":"Pineda de las Infantas y Villatoro","sequence":"additional","affiliation":[{"name":"Department of Medicinal & Organic Chemistry and Excellence Research Unit of \u201cChemistry Applied to Biomedicine and the Environment\u201d, Faculty of Pharmacy, University of Granada, Campus de Cartuja s\/n, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3704-9874","authenticated-orcid":false,"given":"Luis","family":"Izquierdo","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), Hospital Cl\u00ednic\u2014University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4466-7969","authenticated-orcid":false,"given":"Julio","family":"Alonso-Padilla","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), Hospital Cl\u00ednic\u2014University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,1]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2021, March 10). World Malaria Report 2015. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789241565721."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.4269\/ajtmh.16-0141","article-title":"Global epidemiology of Plasmodium vivax","volume":"95","author":"Howes","year":"2016","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_3","unstructured":"(2015). Guidelines for the Treatment of Malaria, World Health Organization. [3rd ed.]."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/nm.4381","article-title":"Antimalarial drug resistance: Linking Plasmodium falciparum parasite biology to the clinic","volume":"23","author":"Blasco","year":"2017","journal-title":"Nat. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1056\/NEJMoa0808859","article-title":"Artemisinin resistance in Plasmodium falciparum malaria","volume":"361","author":"Dondorp","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1056\/NEJMoa1314981","article-title":"Spread of artemisinin resistance in Plasmodium falciparum malaria","volume":"371","author":"Ashley","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_7","unstructured":"World Health Organization (WHO) (2020, March 10). Chagas Disease (American Trypanosomiasis). Available online: https:\/\/www.who.int\/en\/news-room\/fact-sheets\/detail\/chagas-disease-(american-trypanosomiasis)."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.actatropica.2009.07.019","article-title":"Chagas disease in Spain, the United States and other non-endemic countries","volume":"115","author":"Gascon","year":"2010","journal-title":"Acta Trop."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1007\/s40264-018-0696-5","article-title":"Safety profile of benznidazole in the treatment of chronic Chagas disease: Experience of a referral centre and systematic literature review with meta-analysis","volume":"41","author":"Norman","year":"2018","journal-title":"Drug Saf."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1093\/cid\/ciw477","article-title":"Safety profile of nifurtimox for treatment of Chagas disease in the United States","volume":"63","author":"Forsyth","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","first-page":"947","article-title":"Emerging agents for the treatment of Chagas disease: What is in the preclinical and clinical development pipeline?","volume":"9","author":"Urbina","year":"2020","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.2174\/092986710791556023","article-title":"Inhibitors of the purine salvage pathway: A valuable approach for antiprotozoal chemotherapy?","volume":"17","author":"Berg","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"31221","DOI":"10.1074\/jbc.M404232200","article-title":"Purine salvage pathways in the apicomplexan parasite Toxoplasma gondii","volume":"279","author":"Chaudhary","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0166-6851(81)90049-9","article-title":"Purine metabolism in Trypanosoma cruzi","volume":"3","author":"Berens","year":"1981","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0163-7258(03)00071-8","article-title":"Potential chemotherapeutic targets in the purine metabolism of parasites","volume":"99","year":"2003","journal-title":"Pharmacol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1128\/EC.00159-08","article-title":"Purine salvage pathways in the intraerythrocytic malaria parasite Plasmodium falciparum","volume":"7","author":"Downie","year":"2008","journal-title":"Eukaryotic Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8365","DOI":"10.1021\/acs.jmedchem.9b00182","article-title":"Plasmodium purine metabolism and its inhibition by nucleoside and nucleotide analogues","volume":"62","author":"Cheviet","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/S1074-5521(00)00045-4","article-title":"Efficient identification of inhibitors targeting the closed active site conformation of the HPRT from Trypanosoma cruzi","volume":"7","author":"Freymann","year":"2000","journal-title":"Chem. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4501","DOI":"10.1016\/j.bmcl.2004.06.042","article-title":"The purine transferase from Trypanosoma cruzi as a potential target for bisphosphonate-based chemotherapeutic compounds","volume":"14","author":"Wenck","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.pt.2003.09.001","article-title":"Specific chemotherapy of Chagas disease: Controversies and advances","volume":"19","author":"Urbina","year":"2003","journal-title":"Trends Parasitol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1128\/AAC.41.8.1686","article-title":"Hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi as a target for structure-based inhibitor design: Crystallization and inhibition studies with purine analogs","volume":"41","author":"Eakin","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1517\/13543776.15.8.987","article-title":"Purine analogues as antiparasitic agents","volume":"15","author":"Lawton","year":"2005","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1039\/C8MD00098K","article-title":"Synthesis and antiplasmodial activity of purine-based C-nucleoside analogues","volume":"9","author":"Singh","year":"2018","journal-title":"Med. Chem. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9287","DOI":"10.1021\/acs.jmedchem.8b00999","article-title":"Discovery of novel 7-aryl 7-deazapurine 3\u2032-deoxy-ribofuranosyl nucleosides with potent activity against Trypanosoma cruzi","volume":"61","author":"Hulpia","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8069","DOI":"10.1021\/acs.jmedchem.0c00131","article-title":"\u03b2-Hydroxy- and \u03b2-aminophosphonate acyclonucleosides as potent inhibitors of Plasmodium falciparum growth","volume":"63","author":"Cheviet","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1016\/j.bmc.2017.02.016","article-title":"Synthesis and activity of nucleoside-based antiprotozoan compounds","volume":"25","author":"Tran","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"58","DOI":"10.4269\/ajtmh.2007.76.58","article-title":"Specific treatment for Trypanosoma cruzi: Lack of efficacy of allopurinol in the human chronic phase of Chagas disease","volume":"76","author":"Rassi","year":"2007","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9139","DOI":"10.1038\/srep09139","article-title":"Amide-controlled, one-pot synthesis of tri-substituted purines generates structural diversity and analogues with trypanocidal activity","volume":"5","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lorente-Mac\u00edas, \u00c1., D\u00edaz-Moch\u00f3n, J.J., Pineda de las Infantas y Villatoro, M.J., and Unciti-Broceta, A. (2021). Design and synthesis of 9-dialkylamino-6-[(1H-1,2,3-triazol-4-yl)methoxy]-9H-purines. ChemRxiv, preprint.","DOI":"10.26434\/chemrxiv.13664516.v1"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1002\/mrc.4743","article-title":"1 H and 13 C assignments of 6-, 8-, 9- substituted purines","volume":"56","author":"Molina","year":"2018","journal-title":"Magn. Reson. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1186\/s13071-020-04171-6","article-title":"Amaryllidaceae alkaloids with anti-Trypanosoma cruzi activity","volume":"13","author":"Pinazo","year":"2020","journal-title":"Parasit. Vectors"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Bettiol, E., Samanovic, M., Murkin, A.S., Raper, J., Buckner, F., and Rodriguez, A. (2009). Identification of three classes of heteroaromatic compounds with activity against intracellular Trypanosoma cruzi by chemical library screening. PLoS Negl. Trop. Dis., 3.","DOI":"10.1371\/journal.pntd.0000384"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8771","DOI":"10.1038\/srep08771","article-title":"New compound sets identified from high throughput phenotypic screening against three kinetoplastid parasites: An open resource","volume":"5","author":"Cantizani","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1007\/s12272-014-0502-6","article-title":"HepG2 cells as an in vitro model for evaluation of cytochrome P450 induction by xenobiotics","volume":"38","author":"Choi","year":"2015","journal-title":"Arch Pharm Res"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0022-1759(93)90011-U","article-title":"The use of ATP bioluminescence as a measure of cell proliferation and cytotoxicity","volume":"160","author":"Crouch","year":"1993","journal-title":"J. Immunol. Methods"},{"key":"ref_36","unstructured":"Lorente-Mac\u00edas, \u00c1. (2019). Design, Synthesis and Biological Evaluation of 6-Alkoxypurine Derivatives as Kinase Inhibitors. [Ph.D. Thesis, University of Granada]."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S0006-2952(01)00644-X","article-title":"Structure-activity relationships and inhibitory effects of various purine derivatives on the in vitro growth of Plasmodium falciparum","volume":"62","author":"Harmse","year":"2001","journal-title":"Biochem. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.ejmech.2019.01.047","article-title":"Triazole derivatives and their antiplasmodial and antimalarial activities","volume":"166","author":"Chu","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1111\/cbdd.13333","article-title":"New 1,2,3-triazole-based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations","volume":"92","author":"Leite","year":"2018","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s10863-018-9746-z","article-title":"Searching for new drugs for Chagas diseases: Triazole analogs display high in vitro activity against Trypanosoma cruzi and low toxicity toward mammalian cells","volume":"50","author":"Faria","year":"2018","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"17120","DOI":"10.1021\/bi9821465","article-title":"Approaching the transition state in the crystal structure of a phosphoribosyltransferase","volume":"37","author":"Focia","year":"1998","journal-title":"Biochemistry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1039\/C7MD00381A","article-title":"A systematic analysis of atomic protein-ligand interactions in the PDB","volume":"8","author":"Schapira","year":"2017","journal-title":"Med. Chem. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/9367","article-title":"Transition-state analogs as inhibitors of human and malarial hypoxanthine-guanine phosphoribosyltransferases","volume":"6","author":"Li","year":"1999","journal-title":"Nat. Struct. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1021\/acsinfecdis.7b00172","article-title":"Immucillins in infectious diseases","volume":"4","author":"Evans","year":"2018","journal-title":"AC Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Cassera, M.B., Hazleton, K.Z., Merino, E.F., Obaldia, N., Ho, M.C., Murkin, A.S., DePinto, R., Gutierrez, J.A., Almo, S.C., and Evans, G.B. (2011). Plasmodium falciparum parasites are killed by a transition state analogue of purine nucleoside phosphorylase in a primate animal model. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026916"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1016\/j.bmc.2011.12.034","article-title":"Synthesis of purine N 9-[2-hydroxy-3-O-(phosphonomethoxy)propyl] derivatives and their side-chain modified analogs as potential antimalarial agents","volume":"20","author":"Keough","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/0092-8674(94)90301-8","article-title":"The crystal structure of human hypoxanthine-guanine phosphoribosyltransferase with bound GMP","volume":"78","author":"Eads","year":"1994","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5224","DOI":"10.1039\/C5OB00230C","article-title":"Synthesis of 6,8,9 poly-substituted purine analogue libraries as pro-apoptotic inducers of human leukemic lymphocytes and dapk-1 inhibitors","volume":"13","author":"Gallo","year":"2015","journal-title":"Org. Biomol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lorente-Mac\u00edas, \u00c1., Ia\u00f1ez, I., Jim\u00e9nez-L\u00f3pez, M.C., Ben\u00edtez-Quesada, M., Torres-Rusillo, S., D\u00edaz-Moch\u00f3n, J.J., Molina, I.J., and Pineda de las Infantas, M.J. (2021). Synthesis and screening of 6-alkoxy purine analogs as cell type-selective apoptotic inducers in Jurkat cells. Arch. Pharm., e2100095.","DOI":"10.1002\/ardp.202100095"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1126\/science.781840","article-title":"Human malaria parasites in continuous culture","volume":"193","author":"Trager","year":"1976","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"418","DOI":"10.2307\/3280287","article-title":"Synchronization of Plasmodium falciparum erythrocytic stages in culture","volume":"65","author":"Lambros","year":"1979","journal-title":"J. Parasitol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1128\/AAC.40.11.2592","article-title":"Efficient technique for screening drugs for activity against Trypanosoma cruzi using parasites expressing \u03b2-galactosidase","volume":"40","author":"Buckner","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1177\/108705719900400206","article-title":"A simple statistical parameter for use in evaluation and validation of high throughput screening assays","volume":"4","author":"Zhang","year":"1999","journal-title":"J. Biomol. Screen."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ijpddr.2020.07.002","article-title":"Repurposing bioenergetic modulators against protozoan parasites responsible for tropical diseases","volume":"14","author":"Galizzi","year":"2020","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Martinez-Peinado, N., Martori, C., Cortes-Serra, N., Sherman, J., Rodriguez, A., Gascon, J., Alberola, J., Pinazo, M.J., Rodriguez-Cortes, A., and Alonso-Padilla, J. (2021). Anti-Trypanosoma cruzi activity of metabolism modifier compounds. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020688"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/978-1-4939-7737-6_5","article-title":"EuPathDB: The Eukaryotic Pathogen Genomics Database Resource","volume":"1757","author":"Warrenfeltz","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"D539","DOI":"10.1093\/nar\/gkn814","article-title":"PlasmoDB: A functional genomic database for malaria parasites","volume":"37","author":"Aurrecoechea","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"D457","DOI":"10.1093\/nar\/gkp851","article-title":"TriTrypDB: A functional genomic resource for the Trypanosomatidae","volume":"38","author":"Aslett","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"NCBI Resource Coordinators (2018). Database resources of the National Center for Biotechnology Information. Nucleic Acids Res., 46, D8\u2013D13.","DOI":"10.1093\/nar\/gkx1095"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Camacho, C., Coulouris, G., Avagyan, V., Ma, N., Papadopoulos, J., Bealer, K., and Madden, T.L. (2009). BLAST+: Architecture and applications. BMC Bioinform., 10.","DOI":"10.1186\/1471-2105-10-421"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1006\/jmbi.1993.1626","article-title":"Comparative protein modelling by satisfaction of spatial restraints","volume":"234","author":"Blundell","year":"1993","journal-title":"J. Mol. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S0076-6879(03)74020-8","article-title":"MODELLER: Generation and refinement of homology-based protein structure models","volume":"374","author":"Fiser","year":"2003","journal-title":"Methods Enzymol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3982","DOI":"10.1093\/nar\/gkg460","article-title":"Comparative protein structure modeling by iterative alignment, model building and model assessment","volume":"31","author":"John","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1110\/ps.062416606","article-title":"Statistical potential for assessment and prediction of protein structures","volume":"15","author":"Shen","year":"2006","journal-title":"Protein Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"D1388","DOI":"10.1093\/nar\/gkaa971","article-title":"PubChem in 2021: New data content and improved web interfaces","volume":"49","author":"Kim","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1093\/protein\/8.2.127","article-title":"LIGPLOT: A program to generate schematic diagrams of protein-ligand interactions","volume":"8","author":"Wallace","year":"1995","journal-title":"Prot. Eng."},{"key":"ref_70","unstructured":"DeLano, W.L. (2002). The PyMOL Molecular Graphics System, DeLano Scientific LLC. Available online: www.pymol.org\/."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0022-2836(82)90515-0","article-title":"A simple method for displaying the hydropathic character of a protein","volume":"157","author":"Kyte","year":"1982","journal-title":"J. Mol. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/pro.3280","article-title":"Improvements to the APBS biomolecular solvation software suite","volume":"27","author":"Jurrus","year":"2018","journal-title":"Protein Sci."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/7\/638\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:24:34Z","timestamp":1760163874000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/7\/638"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,1]]},"references-count":72,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["ph14070638"],"URL":"https:\/\/doi.org\/10.3390\/ph14070638","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,1]]}}}