{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T18:07:11Z","timestamp":1765994831343,"version":"build-2065373602"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100019382","name":"Fundacion Instituto De Inmunologia De Colombia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019382","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT 2015-0898"],"award-info":[{"award-number":["PICT 2015-0898"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005363","name":"Universidad de Buenos Aires","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochemical Pharmacology"],"published-print":{"date-parts":[[2021,6]]},"DOI":"10.1016\/j.bcp.2021.114524","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T17:44:32Z","timestamp":1616003072000},"page":"114524","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"special_numbering":"C","title":["Zoledronate repositioning as a potential trypanocidal drug. Trypanosoma cruzi HPRT an alternative target to be considered"],"prefix":"10.1016","volume":"188","author":[{"given":"W.M.","family":"Valsecchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.M.","family":"Delfino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1140-8234","authenticated-orcid":false,"given":"J.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.H.","family":"Fern\u00e1ndez Villamil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.bcp.2021.114524_b0005","first-page":"11","article-title":"Developments on treatment of Chagas disease \u2013 from discovery to current times","volume":"23","author":"Custodio-Leite","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"10.1016\/j.bcp.2021.114524_b0010","article-title":"Repositioning of leishmanicidal [1,2,3]Triazolo[1,5-a]pyridinium salts for Chagas disease treatment: Trypanosoma cruzi cell death involving mitochondrial membrane depolarisation and Fe-SOD inhibition","author":"Mart\u00edn-Escolano","year":"2020","journal-title":"Protozool. Res."},{"key":"10.1016\/j.bcp.2021.114524_b0015","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.actatropica.2009.10.023","article-title":"Specific chemotherapy of Chagas disease: relevance, current limitations and new approaches","volume":"115","author":"Urbina","year":"2010","journal-title":"Acta Trop."},{"key":"10.1016\/j.bcp.2021.114524_b0020","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."},{"issue":"1","key":"10.1016\/j.bcp.2021.114524_b0025","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1021\/acschembio.7b00916","article-title":"The design of Plasmodium vivax hypoxanthine-guanine phosphoribosyltransferase inhibitors as potential antimalarial therapeutics","volume":"13","author":"Keough","year":"2018","journal-title":"ACS Chem. Biol."},{"issue":"23","key":"10.1016\/j.bcp.2021.114524_b0030","doi-asserted-by":"crossref","first-page":"16084","DOI":"10.1074\/jbc.M600188200","article-title":"A conditional mutant deficient in hypoxanthine-guanine phosphoribosyltransferase and xanthine phosphoribosyltransferase validates the purine salvage pathway of Leishmania donovani","volume":"281","author":"Boitz","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bcp.2021.114524_b0035","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0166-6851(93)90039-Z","article-title":"Inhibition of Plasmodium falciparum hypoxanthine-guanine phosphoribosyltransferase mRNA by antisense oligodeoxynucleotide sequence","volume":"60","author":"Dawson","year":"1993","journal-title":"Mol. Biochem. Parasitol."},{"key":"10.1016\/j.bcp.2021.114524_b0040","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."},{"issue":"47","key":"10.1016\/j.bcp.2021.114524_b0045","doi-asserted-by":"crossref","first-page":"40706","DOI":"10.1074\/jbc.M111.291138","article-title":"Structural analyses of a purine biosynthetic enzyme from Mycobacterium tuberculosis Reveal a novel bound nucleotide","volume":"286","author":"Le Nours","year":"2011","journal-title":"J. Biol. Chem."},{"issue":"6","key":"10.1016\/j.bcp.2021.114524_b0050","first-page":"6","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":"10.1016\/j.bcp.2021.114524_b0055","first-page":"655","article-title":"The role of the C-terminal region on the oligomeric state and enzymatic activity of Trypanosoma cruzi hypoxanthine phosphoribosyl transferase","volume":"1864","author":"Valsecchi","year":"2016","journal-title":"BBA"},{"key":"10.1016\/j.bcp.2021.114524_b0060","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":"Fern\u00e1ndez","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bcp.2021.114524_b0065","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s00198-007-0540-8","article-title":"Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy","volume":"19","author":"Russell","year":"2008","journal-title":"Osteoporos. Int."},{"issue":"22","key":"10.1016\/j.bcp.2021.114524_b0070","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1056\/NEJM199511303332201","article-title":"Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group","volume":"333","author":"Liberman","year":"1995","journal-title":"New Engl. J. Med."},{"issue":"1","key":"10.1016\/j.bcp.2021.114524_b0075","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.amjmed.2012.06.023","article-title":"Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday","volume":"126","author":"McClung","year":"2013","journal-title":"Am. J. Med."},{"issue":"7","key":"10.1016\/j.bcp.2021.114524_b0080","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1093\/jnci\/djz215","article-title":"Phase III randomized trial of bisphosphonates as adjuvant therapy in breast cancer: S0307","volume":"112","author":"Gralow","year":"2020","journal-title":"J. Natl. Cancer Inst."},{"key":"10.1016\/j.bcp.2021.114524_b0085","first-page":"4","article-title":"Symptomatic hypocalcemia following a single dose of zoledronic acid in a patient with bone metastases secondary to breast cancer","author":"S\u00f6zel","year":"2020","journal-title":"J. Oncol.gy Pharmacy Practice"},{"key":"10.1016\/j.bcp.2021.114524_b0090","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s00167-019-05598-w","article-title":"Zoledronic acid is more efficient than ibandronic acid in the treatment of symptomatic bone marrow lesions of the knee","volume":"28","author":"M\u00fcller","year":"2020","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"issue":"15","key":"10.1016\/j.bcp.2021.114524_b0095","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1001\/jama.2020.2938","article-title":"Effect of intravenous zoledronic acid on tibiofemoral cartilage volume among patients with knee osteoarthritis with bone marrow lesions: a randomized clinical trial","volume":"323","author":"Cai","year":"2020","journal-title":"JAMA"},{"key":"10.1016\/j.bcp.2021.114524_b0100","first-page":"6","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":"Microbiology"},{"issue":"9","key":"10.1016\/j.bcp.2021.114524_b0105","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1371\/journal.pntd.0006764","article-title":"Anti-parasitic effect of vitamin C alone and in combination with benznidazole against Trypanosoma cruzi","volume":"12","author":"Puente","year":"2018","journal-title":"PLoS Negl. Trop. Dis."},{"key":"10.1016\/j.bcp.2021.114524_b0110","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.exppara.2012.09.002","article-title":"Functional characterization of TcCYC2 cyclin from Trypanosoma cruzi","volume":"132","author":"Potenza","year":"2012","journal-title":"Exp. Parasitol."},{"issue":"36","key":"10.1016\/j.bcp.2021.114524_b0115","first-page":"2","article-title":"Chagas disease treatment: from new therapeutic targets to drug discovery and repositioning","volume":"26","author":"Miranda","year":"2019","journal-title":"Edit. Curr. Med. Chem."},{"issue":"4","key":"10.1016\/j.bcp.2021.114524_b0120","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijantimicag.2020.105906","article-title":"Searching drugs for Chagas disease, leishmaniasis and schistosomiasis: a brief review","volume":"55","author":"Santos","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"10.1016\/j.bcp.2021.114524_b0125","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.ijantimicag.2003.07.020","article-title":"Selective in vitro effects of the farnesyl pyrophosphate synthase inhibitor risedronate on Trypanosoma cruzi","volume":"23","author":"Garzoni","year":"2004","journal-title":"Int. J. Antimicrob. Agents"},{"issue":"19","key":"10.1016\/j.bcp.2021.114524_b0130","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1016\/S0960-894X(03)00663-2","article-title":"Bisphosphonates derived from fatty acids are potent inhibitors of Trypanosoma cruzi farnesyl pyrophosphate synthase","volume":"13","author":"Szajnman","year":"2003","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bcp.2021.114524_b0135","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s00775-018-1535-y","article-title":"Ibandronate metal complexes: solution behavior and antiparasitic activity","volume":"23","author":"Demoro","year":"2018","journal-title":"J. Biol. Inorg. Chem."},{"key":"10.1016\/j.bcp.2021.114524_b0140","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1155\/2016\/9025627","article-title":"Studies of the effectiveness of bisphosphonate and vanadium-bisphosphonate compounds in vitro against axenic Leishmania tarentolae","volume":"2016","author":"Christensen","year":"2016","journal-title":"Oxid. Med. Cell. Longevity"},{"issue":"12","key":"10.1016\/j.bcp.2021.114524_b0145","doi-asserted-by":"crossref","first-page":"7530","DOI":"10.1128\/AAC.01873-15","article-title":"In vitro and in vivo investigation of the inhibition of Trypanosoma brucei cell growth by lipophilic bisphosphonates","volume":"59","author":"Yang","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.bcp.2021.114524_b0150","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1021\/jm030084x","article-title":"Effects of bisphosphonates on the growth of Entamoeba histolytica and Plasmodium species in vitro and in vivo","volume":"47","author":"Ghosh","year":"2004","journal-title":"J. Med. Chem."},{"issue":"11","key":"10.1016\/j.bcp.2021.114524_b0155","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1073\/pnas.1118215109","article-title":"Lipophilic analogs of zoledronate and risedronate inhibit Plasmodium geranylgeranyl diphosphate synthase (GGPPS) and exhibit potent antimalarial activity","volume":"109","author":"No","year":"2012","journal-title":"PNAS"},{"issue":"8","key":"10.1016\/j.bcp.2021.114524_b0160","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/AAC.02628-16","article-title":"Synergistic activity between statins and bisphosphonates against acute experimental toxoplasmosis","volume":"61","author":"Li","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"issue":"7","key":"10.1016\/j.bcp.2021.114524_b0165","first-page":"38","article-title":"Clinical evaluation of cost efficacy of drugs for treatment of osteoporosis: a meta-analysis","volume":"27","author":"Albert","year":"2017","journal-title":"Endrocrine Practice"},{"key":"10.1016\/j.bcp.2021.114524_b0170","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.semcancer.2019.12.001","article-title":"Repurposing amino-bisphosphonates by liposome formulation for a new role in cancer treatment","volume":"68","author":"La-Beck","year":"2021","journal-title":"Semin. Cancer Biol."},{"issue":"4","key":"10.1016\/j.bcp.2021.114524_b0175","first-page":"5","article-title":"Intravenous zoledronate for osteoporosis: less might be more","volume":"8","author":"Grey","year":"2016","journal-title":"Therap. Adv. Musculoskeletal Dis."},{"key":"10.1016\/j.bcp.2021.114524_b0180","first-page":"7","article-title":"Standardized Arrabidaea chica extract shows cytoprotective effects in zoledronic acid-treated fibroblasts and osteoblasts","volume":"12","author":"Wiziack-Zago","year":"2020","journal-title":"Clin., Cosm. Investig. Dent."},{"key":"10.1016\/j.bcp.2021.114524_b0185","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/jop.12181","article-title":"Zoledronic acid and geranylgeraniol regulate cellular behaviour and angiogenic gene expression in human gingival fibroblasts","volume":"43","author":"Zafar","year":"2014","journal-title":"J. Oral Pathol. Med."},{"key":"10.1016\/j.bcp.2021.114524_b0190","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1177\/0091270002239824","article-title":"The pharmacokinetics and pharmacodynamics of zoledronic acid in cancer patients with varying degrees of renal function","volume":"43","author":"Skerjanec","year":"2003","journal-title":"J. Clin. Pharmacol."},{"issue":"19","key":"10.1016\/j.bcp.2021.114524_b0195","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.bmc.2015.08.014","article-title":"Discovery of potent nitrotriazole-based antitrypanosomal agents: In vitro and in vivo evaluation","volume":"23","author":"Papadopoulou","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bcp.2021.114524_b0200","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2174\/0929867323999160625124424","article-title":"Challenges in chagas disease drug discovery: a review","volume":"23","author":"Paucar","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.bcp.2021.114524_b0205","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/nrd2144","article-title":"Innovative lead discovery strategies for tropical diseases","volume":"5","author":"Nwaka","year":"2006","journal-title":"Nat. Rev. Drug Discovery"},{"key":"10.1016\/j.bcp.2021.114524_b0210","first-page":"7","article-title":"Repurposing strategies for Chagas disease therapy: the effect of imatinib and derivatives against Trypanosoma cruzi","author":"Sim\u00f5es-Silva","year":"2019","journal-title":"Parasitolgy"},{"issue":"14","key":"10.1016\/j.bcp.2021.114524_b0215","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1021\/jm00066a014","article-title":"Toward a novel metal-based chemotherapy against tropical diseases. 1. Enhancement of the efficacy of clotrimazole against Trypanosoma cruzi by complexation to ruthenium in RuCl2(clotrimazole)","volume":"36","author":"S\u00e1nchez-Delgado","year":"1993","journal-title":"J. Med. Chem."},{"issue":"20","key":"10.1016\/j.bcp.2021.114524_b0220","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1056\/NEJMoa1313122","article-title":"Randomized trial of posaconazole and benznidazole for chronic Chagas\u2019 disease","volume":"370","author":"Molina","year":"2014","journal-title":"New England J. Med."},{"issue":"1","key":"10.1016\/j.bcp.2021.114524_b0225","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1371\/journal.pntd.0007481","article-title":"Crystal violet structural analogues identified by in silico drug repositioning present anti-Trypanosoma cruzi activity through inhibition of proline transporter TcAAAP069","volume":"14","author":"Say\u00e9","year":"2020","journal-title":"PLoS Negl. Trop. Dis."}],"container-title":["Biochemical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295221001209?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295221001209?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T15:08:33Z","timestamp":1762096113000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006295221001209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6]]},"references-count":45,"alternative-id":["S0006295221001209"],"URL":"https:\/\/doi.org\/10.1016\/j.bcp.2021.114524","relation":{},"ISSN":["0006-2952"],"issn-type":[{"type":"print","value":"0006-2952"}],"subject":[],"published":{"date-parts":[[2021,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Zoledronate repositioning as a potential trypanocidal drug. Trypanosoma cruzi HPRT an alternative target to be considered","name":"articletitle","label":"Article Title"},{"value":"Biochemical Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bcp.2021.114524","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"114524"}}