{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:54:33Z","timestamp":1791928473318,"version":"4.3.4"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T00:00:00Z","timestamp":1597708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["17\/08684-7"],"award-info":[{"award-number":["17\/08684-7"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E-26\/010.101106\/2018"],"award-info":[{"award-number":["E-26\/010.101106\/2018"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E-26\/203.191\/2017"],"award-info":[{"award-number":["E-26\/203.191\/2017"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["145654\/2019-2"],"award-info":[{"award-number":["145654\/2019-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The search for new compounds with antimalarial activity is urgent, as resistance to ones in the classical drug, has already been described in more than one continent. Compounds derived from 1,2,3-triazoles are effective against parasites and bacteria. Here, we evaluated the potential antimalarial activity against the human malaria parasite Plasmodium falciparum in a culture of fifty-four triazole compounds derived from 1H-and 2H-1,2,3-triazole. We identified thirty-one compounds with potential antimalarial activity at concentrations in the micromolar order (\u00b5M) and IC50 values ranging from 2.80 \u00b5M (9) to 29.27 \u00b5M (21). Then, we selected some of these compounds to perform the same tests on the PfSR25- strain (knockout for P. falciparum G-protein coupled receptor-like, SR25). Our experiences with the PfSR25- strain showed that both compounds with higher antimalarial activity for the 3D7 strain and those with less activity resulted in lower IC50 values for the knockout strain. The cytotoxicity of the compounds was evaluated in human renal embryonic cells (HEK 293), using MTT assays. This demonstrated that the compounds with the highest activity (9, 13, 19, 22, 24, 29), showed no toxicity at the tested concentrations.<\/jats:p>","DOI":"10.3390\/biom10081197","type":"journal-article","created":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T11:15:27Z","timestamp":1597749327000},"page":"1197","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Plasmodium falciparum Knockout for the GPCR-Like PfSR25 Receptor Displays Greater Susceptibility to 1,2,3-Triazole Compounds That Block Malaria Parasite Development"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2196-260X","authenticated-orcid":false,"given":"Benedito","family":"Santos","sequence":"first","affiliation":[{"name":"Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo-SP 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Gonzaga","sequence":"additional","affiliation":[{"name":"Funda\u00e7\u00e3o Centro Universit\u00e1rio Estadual da Zona Oeste, Unidade de Farm\u00e1cia, Rio de Janeiro-RJ 23070-200, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2042-3778","authenticated-orcid":false,"given":"Fernando","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Institute of Chemistry, Universidade Federal Fluminense, Niter\u00f3i-RJ 24220-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2166-766X","authenticated-orcid":false,"given":"Vitor","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Pharmacy School, Universidade Federal Fluminense, Niter\u00f3i-RJ 24220-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo-SP 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms1558","article-title":"Global kinomic and phospho-proteomic analyses of the human malaria parasite Plasmodium falciparum","volume":"2","author":"Solyakov","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_2","unstructured":"WHO (2020, April 13). Fact Sheet about Malaria. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/malaria."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/nm.3073","article-title":"Malaria biology and disease pathogenesis: Insights for new treatments","volume":"19","author":"Miller","year":"2013","journal-title":"Nat. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1093\/molbev\/msh205","article-title":"The malaria parasite\u2019s chloroquine resistance transporter is a member of the drug\/metabolite transporter superfamily","volume":"21","author":"Martin","year":"2004","journal-title":"Mol. Biol. Evol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1126\/science.1074045","article-title":"Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations","volume":"298","author":"Fidock","year":"2002","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1126\/science.1175667","article-title":"Chloroquine Transport via the Malaria Parasite\u2019s Chloroquine Resistance Transporter","volume":"325","author":"Martin","year":"2009","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"E1759","DOI":"10.1073\/pnas.1322965111","article-title":"Diverse mutational pathways converge on saturable chloroquine transport via the malaria parasite\u2019s chloroquine resistance transporter","volume":"111","author":"Summers","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3356","DOI":"10.1073\/pnas.1417102112","article-title":"Plasmodium falciparum chloroquine resistance transporter is a H +-coupled polyspecific nutrient and drug exporter","volume":"112","author":"Juge","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","unstructured":"World Health Organization (WHO) (2017). Artemisinin and Artemisinin-Based Combination Therapy Resistance: Status Report, World Health Organisation."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/ng.3189","article-title":"Genetic architecture of artemisinin-resistant Plasmodium falciparum","volume":"47","author":"Miotto","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Neher, R.A., and MalariaGEN Plasmodium falciparum Community Project (2016). Genomic epidemiology of artemisinin resistant malaria. Elife.","DOI":"10.7554\/eLife.08714.029"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1517\/13543776.11.2.185","article-title":"Quinoline antimalarials","volume":"11","author":"Egan","year":"2001","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"479","DOI":"10.2174\/156802606776743147","article-title":"A Medicinal Chemistry Perspective on 4-Aminoquinoline Antimalarial Drugs","volume":"6","author":"Bray","year":"2006","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep22093","article-title":"Biliverdin targets enolase and eukaryotic initiation factor 2 (eIF2\u03b1) to reduce the growth of intraerythrocytic development of the malaria parasite Plasmodium falciparum","volume":"6","author":"Alves","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"37793","DOI":"10.1074\/jbc.M112.414078","article-title":"Direct tests of enzymatic heme degradation by the malaria parasite Plasmodium falciparum","volume":"287","author":"Sigala","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1186\/1475-2875-12-234","article-title":"Biological evaluation of hydroxynaphthoquinones as anti-malarials","volume":"12","author":"Schuck","year":"2013","journal-title":"Malar. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.ejmech.2014.03.059","article-title":"2-Aryl-3H-indol-3-ones: Synthesis, electrochemical behaviour and antiplasmodial activities","volume":"78","author":"Najahi","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.ejmech.2014.03.055","article-title":"Synthetic indole and melatonin derivatives exhibit antimalarial activity on the cell cycle of the human malaria parasite Plasmodium falciparum","volume":"78","author":"Schuck","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1002\/jhet.3234","article-title":"Quinolone\u2013Triazole Hybrids and their Biological Activities","volume":"55","author":"Xu","year":"2018","journal-title":"J. Heterocycl. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1016\/j.drudis.2017.05.014","article-title":"The 1,2,3-triazole ring as a bioisostere in medicinal chemistry","volume":"22","author":"Bonandi","year":"2017","journal-title":"Drug Discov. Today"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S0168-6445(99)00039-X","article-title":"Molecular basis of antibiotic resistance and \u03b2-lactamase inhibition by mechanism-based inactivators: Perspectives and future directions","volume":"24","author":"Therrien","year":"2000","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1111\/cbdd.12321","article-title":"New compounds hybrids 1H-1,2,3-triazole-quinoline against plasmodium falciparum","volume":"84","author":"Boechat","year":"2014","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.bmc.2016.10.029","article-title":"Synthesis and evaluation of naphthyl bearing 1,2,3-triazole analogs as antiplasmodial agents, cytotoxicity and docking studies","volume":"25","author":"Saikrishn","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.3762\/bjoc.7.205","article-title":"Synthesis of 2-amino-3-arylpropan-1-ols and 1-(2,3-diaminopropyl)-1,2,3-triazoles and evaluation of their antimalarial activity","volume":"7","author":"Vandekerckhove","year":"2011","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.ejmech.2013.08.046","article-title":"In vitro antimalarial activity, \u03b2-haematin inhibition and structure\u2013activity relationships in a series of quinoline triazoles","volume":"69","author":"Joshi","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.ejmech.2017.12.051","article-title":"Antimalarial naphthoquinones. Synthesis via click chemistry, in vitro activity, docking to PfDHODH and SAR of lapachol-based compounds","volume":"145","author":"Missias","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Moraes, M.S., Budu, A., Singh, M.K., Borges-Pereira, L., Levano-Garcia, J., Curr\u00e0, C., Picci, L., Pace, T., Ponzi, M., and Pozzan, T. (2017). Plasmodium falciparum GPCR-like receptor SR25 mediates extracellular K+ sensing coupled to Ca2+ signaling and stress survival. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-09959-8"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5988","DOI":"10.1021\/jm2003624","article-title":"Novel 1,2,3-triazole derivatives for use against mycobacterium tuberculosis H37Rv (ATCC 27294) strain","volume":"54","author":"Boechat","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.ejmech.2013.12.039","article-title":"1-Phenyl-1H- and 2-phenyl-2H-1,2,3-triazol derivatives: Design, synthesis and inhibitory effect on alpha-glycosidases","volume":"74","author":"Gonzaga","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.ejmech.2017.08.034","article-title":"1-Aryl-1 H - and 2-aryl-2 H -1,2,3-triazole derivatives blockade P2X7 receptor in vitro and inflammatory response in vivo","volume":"139","author":"Gonzaga","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.1096\/fj.11-187401","article-title":"Identifying apicoplast-targeting antimalarials using high-throughput compatible approaches","volume":"25","author":"Ekland","year":"2011","journal-title":"FASEB J."},{"key":"ref_35","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_36","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1006\/jsbi.1997.3886","article-title":"Imaging Plasmodium falciparum-infected ghost and parasite by atomic force microscopy","volume":"119","author":"Garcia","year":"1997","journal-title":"J. Struct. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/S1473-3099(16)30415-7","article-title":"A surrogate marker of piperaquine-resistant Plasmodium falciparum malaria: A phenotype\u2013genotype association study","volume":"17","author":"Witkowski","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/35017112","article-title":"Calcium-dependent modulation by melatonin of the circadian rhythm in malarial parasites","volume":"2","author":"Hotta","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1590\/S0100-879X2003001100016","article-title":"Melatonin and N-acetyl-serotonin cross the red blood cell membrane and evoke calcium mobilization in malarial parasites","volume":"36","author":"Hotta","year":"2003","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.chom.2019.06.001","article-title":"Elucidating Mechanisms of Drug-Resistant Plasmodium falciparum","volume":"26","author":"Ross","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1093\/bfgp\/elz008","article-title":"The genomic architecture of antimalarial drug resistance","volume":"18","author":"Cowell","year":"2019","journal-title":"Brief. Funct. Genom."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1038\/sj.emboj.7600681","article-title":"A critical role for PfCRT K76T in Plasmodium falciparum verapamil-reversible chloroquine resistance","volume":"24","author":"Lakshmanan","year":"2005","journal-title":"EMBO J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1038\/s41467-018-05652-0","article-title":"Emerging Southeast Asian PfCRT mutations confer Plasmodium falciparum resistance to the first-line antimalarial piperaquine","volume":"9","author":"Ross","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/S1473-3099(16)30409-1","article-title":"Genetic markers associated with dihydroartemisinin\u2013piperaquine failure in Plasmodium falciparum malaria in Cambodia: A genotype\u2013phenotype association study","volume":"17","author":"Amato","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"326","DOI":"10.36468\/pharmaceutical-sciences.514","article-title":"In silico docking study of Limonoids from Azadirachta indica with pfpk5: A Novel Target for Plasmodium falciparum","volume":"81","author":"Khanal","year":"2019","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s42452-020-2955-1","article-title":"QSAR and molecular docking based design of some indolyl-3-ethanone-\u03b1-thioethers derivatives as Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors","volume":"2","author":"Ibrahim","year":"2020","journal-title":"SN Appl. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Iman, M., Davood, A., and Khamesipour, A. (2019). Design of antimalarial agents based on pyrimidine derivatives as methionine aminopeptidase 1b inhibitor: Molecular docking, quantitative structure activity relationships, and molecular dynamics simulation studies. J. Chin. Chem. Soc., 1\u201311.","DOI":"10.1002\/jccs.201900165"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Madeira, L., Galante, P.A.F., Budu, A., Azevedo, M.F., Malnic, B., and Garcia, C.R.S. (2008). Genome-wide detection of serpentine receptor-like proteins in malaria parasites. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001889"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/8\/1197\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:02:27Z","timestamp":1760176947000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/8\/1197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,18]]},"references-count":48,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["biom10081197"],"URL":"https:\/\/doi.org\/10.3390\/biom10081197","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,18]]}}}