{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:48:01Z","timestamp":1790214481413,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa no Estado do Rio de Janeiro (FAPERJ)","award":["001"],"award-info":[{"award-number":["001"]}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>Leishmaniasis, caused by protozoa of the genus Leishmania, encompasses a group of neglected diseases with diverse clinical and epidemiological manifestations that can be fatal if not adequately and promptly managed\/treated. The current chemotherapy options for this disease are expensive, require invasive administration and often lead to severe side effects. In this regard, our research group has previously reported the potent anti-Leishmania activity of two coordination compounds (complexes) derived from 1,10-phenanthroline-5,6-dione (phendione): [Cu(phendione)3].(ClO4)2.4H2O and [Ag(phendione)2].ClO4. The present study aimed to evaluate the effects of these complexes on leishmanolysin (gp63), a virulence factor produced by all Leishmania species that plays multiple functions and is recognized as a potential target for antiparasitic drugs. The results showed that both Ag-phendione (\u221274.82 kcal\/mol) and Cu-phendione (\u221268.16 kcal\/mol) were capable of interacting with the amino acids comprising the active site of the gp63 protein, exhibiting more favorable interaction energies compared to phendione alone (\u221239.75 kcal\/mol) or 1,10-phenanthroline (\u221245.83 kcal\/mol; a classical gp63 inhibitor) as judged by molecular docking assay. The analysis of kinetic parameters using the fluorogenic substrate Z-Phe-Arg-AMC indicated Vmax and apparent Km values of 0.064 \u00b5M\/s and 14.18 \u00b5M, respectively, for the released gp63. The effects of both complexes on gp63 proteolytic activity were consistent with the in silico assay, where Ag-phendione exhibited the highest gp63 inhibition capacity against gp63, with an IC50 value of 2.16 \u00b5M and the lowest inhibitory constant value (Ki = 5.13 \u00b5M), followed by Cu-phendione (IC50 = 163 \u00b5M and Ki = 27.05 \u00b5M). Notably, pretreatment of live L. amazonensis promastigotes with the complexes resulted in a significant reduction in the expression of gp63 protein, including the isoforms located on the parasite cell surface. Both complexes markedly decreased the in vitro association indexes between L. amazonensis promastigotes and THP-1 human macrophages; however, this effect was reversed by the addition of soluble gp63 molecules to the interaction medium. Collectively, our findings highlight the potential use of these potent complexes in antivirulence therapy against Leishmania, offering new insights for the development of effective treatments for leishmaniasis.<\/jats:p>","DOI":"10.3390\/tropicalmed8070348","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:49:27Z","timestamp":1688345367000},"page":"348","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Silver(I) and Copper(II) 1,10-Phenanthroline-5,6-dione Complexes as Promising Antivirulence Strategy against Leishmania: Focus on Gp63 (Leishmanolysin)"],"prefix":"10.3390","volume":"8","author":[{"given":"Simone S. C.","family":"Oliveira","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Estudos Avan\u00e7ados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de G\u00f3es (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudyane A.","family":"Correia","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Estudos Avan\u00e7ados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de G\u00f3es (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa S.","family":"Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Estudos Avan\u00e7ados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de G\u00f3es (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine F. F.","family":"da Cunha","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Modelagem Molecular, Departamento de Qu\u00edmica, Universidade Federal de Lavras, Lavras 37200-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre A.","family":"de Castro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Modelagem Molecular, Departamento de Qu\u00edmica, Universidade Federal de Lavras, Lavras 37200-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodorico C.","family":"Ramalho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Modelagem Molecular, Departamento de Qu\u00edmica, Universidade Federal de Lavras, Lavras 37200-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Devereux","sequence":"additional","affiliation":[{"name":"The Centre for Biomimetic & Therapeutic Research, Focas Research Institute, Technological University Dublin, D08 CKP1 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malachy","family":"McCann","sequence":"additional","affiliation":[{"name":"Chemistry Department, Maynooth University, W23 F2H6 Maynooth, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9752-8148","authenticated-orcid":false,"given":"Marta H.","family":"Branquinha","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Estudos Avan\u00e7ados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de G\u00f3es (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0821-8592","authenticated-orcid":false,"given":"Andr\u00e9 L. S.","family":"Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Estudos Avan\u00e7ados de Microrganismos Emergentes e Resistentes (LEAMER), Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de G\u00f3es (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-901, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Bioqu\u00edmica (PPGBq), Instituto de Qu\u00edmica (IQ), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-909, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","article-title":"Leishmaniasis","volume":"392","author":"Burza","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.pt.2021.07.003","article-title":"Leishmaniasis: The act of transmission","volume":"37","author":"Serafim","year":"2021","journal-title":"Trends Parasitol."},{"key":"ref_3","unstructured":"(2023, March 15). World Health Organization (WHO) March 2023. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/leishmaniasis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/qjmed\/hct116","article-title":"Leishmaniasis: Clinical syndromes and treatment","volume":"107","author":"McGwire","year":"2014","journal-title":"QJM"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"106018","DOI":"10.1016\/j.actatropica.2021.106018","article-title":"Phenotypical and genotypical differences among Leishmania (Leishmania) amazonensis isolates that caused different clinical frames in humans and dogs: A systematic review","volume":"221","author":"Silva","year":"2021","journal-title":"Acta Trop."},{"key":"ref_6","first-page":"e51","article-title":"Visceral leishmaniasis caused by Leishmania (Leishmania) amazonensis associated with Hodgkin\u2019s lymphoma","volume":"64","author":"Porto","year":"2022","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8965","DOI":"10.1007\/s00253-020-10856-w","article-title":"Recent advances and new strategies on leishmaniasis treatment","volume":"104","author":"Roatt","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"120761","DOI":"10.1016\/j.ijpharm.2021.120761","article-title":"Nanotechnology-aided diagnosis, treatment and prevention of leishmaniasis","volume":"10","author":"Kammona","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Singh, R., Kashif, M., Srivastava, P., and Manna, P.P. (2023). Recent advances in chemotherapeutics for leishmaniasis: Importance of the cellular biochemistry of the parasite and its molecular interaction with the host. Pathogens, 12.","DOI":"10.3390\/pathogens12050706"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"102490","DOI":"10.1016\/j.nano.2021.102490","article-title":"Surfactant free synthesis of cationic nano-vesicles: A safe triple drug loaded vehicle for the topical treatment of cutaneous leishmaniasis","volume":"40","author":"Khalid","year":"2022","journal-title":"Nanomedicine"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.2217\/nnm-2022-0077","article-title":"Triple-combination therapy for cutaneous leishmaniasis using detergent-free, hyaluronate-coated elastic nanovesicles","volume":"17","author":"Iqbal","year":"2022","journal-title":"Nanomedicine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1080\/17425247.2020.1700227","article-title":"Development and evaluation of novel miltefosine-polyphenol co-loaded second-generation nano-transfersomes for the topical treatment of cutaneous leishmaniasis","volume":"17","author":"Dar","year":"2020","journal-title":"Expert. Opin. Drug. Deliv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nrd.2017.23","article-title":"Different drugs for bad bugs: Antivirulence strategies in the age of antibiotic resistance","volume":"16","author":"Dickey","year":"2017","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.sbi.2018.08.010","article-title":"Enzyme targets for drug design of new anti-virulence therapeutics","volume":"53","author":"Kahler","year":"2018","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.2166\/wh.2009.036","article-title":"Virulence factors and their mechanisms of action: The view from a damage-response framework","volume":"1","author":"Casadevall","year":"2009","journal-title":"J. Water Health"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0166-6851(03)00211-1","article-title":"The major surface protease (MSP or GP63) of Leishmania sp. Biosynthesis, regulation of expression, and function","volume":"132","author":"Yao","year":"2003","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"72","DOI":"10.3389\/fcimb.2012.00072","article-title":"Impact of Leishmania metalloprotease GP63 on macrophage signaling","volume":"2","author":"Isnard","year":"2012","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Guay-Vincent, M.M., Matte, C., Berthiaume, A.M., Olivier, M., Jaramillo, M., and Descoteaux, A. (2022). Revisiting Leishmania GP63 host cell targets reveal a limited spectrum of substrates. PLoS Pathog., 18.","DOI":"10.1101\/2022.06.06.494968"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.cellimm.2016.07.013","article-title":"Leishmania exosomes and other virulence factors: Impact on innate immune response and macrophage functions","volume":"309","author":"Atayde","year":"2016","journal-title":"Cell Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"669079","DOI":"10.3389\/fcimb.2021.669079","article-title":"Comparative analysis of virulence mechanisms of trypanosomatids pathogenic to humans","volume":"11","author":"Mortara","year":"2021","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1080\/21505594.2022.2074130","article-title":"The pathogenicity and virulence of Leishmania\u2014Interplay of virulence factors with host defenses","volume":"13","author":"Gupta","year":"2022","journal-title":"Virulence"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1016\/j.micinf.2012.05.014","article-title":"Leishmania virulence factors: Focus on the metalloprotease GP63","volume":"14","author":"Olivier","year":"2012","journal-title":"Microbes Infect."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1017\/S0031182009990540","article-title":"Dissimilar peptidase production by avirulent and virulent promastigotes of Leishmania braziliensis: Inference on the parasite proliferation and interaction with macrophages","volume":"136","author":"Lima","year":"2009","journal-title":"Parasitology"},{"key":"ref_24","first-page":"100093","article-title":"Decoding the anti-Leishmania braziliensis activity of 1,10-phenanthroline-5,6-dione and its silver- and copper-based complexes: In vitro and in vivo approaches","volume":"6","author":"Santos","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Oliveira, S.S.C., Santos, V.S., Devereux, M., McCann, M., Santos, A.L.S., and Branquinha, M.H. (2023). The Anti-Leishmania amazonensis and anti-Leishmania chagasi action of copper(II) and silver(I) 1,10-phenanthroline-5,6-dione coordination compounds. Pathogens, 12.","DOI":"10.3390\/pathogens12010070"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.protis.2017.03.004","article-title":"In vitro inhibition of Leishmania attachment to sandfly midguts and LL-5 cells by divalent metal chelators, anti-gp63 and phosphoglycans","volume":"168","author":"Soares","year":"2017","journal-title":"Protist"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.2174\/092986712800609733","article-title":"Deciphering the antimicrobial activity of phenanthroline chelators","volume":"19","author":"McCann","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1039\/c2tx00010e","article-title":"In vitro and in vivo studies into the biological activities of 1,10-phenanthroline, 1,10-phenanthroline-5,6-dione and its copper(II) and silver(I) complexes","volume":"1","author":"McCann","year":"2012","journal-title":"Toxicology Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s10534-004-1229-5","article-title":"Synthesis and X-ray crystal structure of [Ag(phendio)2]ClO4 (phendio = 1,10-phenanthroline-5,6-dione) and its effects on fungal and mammalian cells","volume":"17","author":"McCann","year":"2004","journal-title":"Biometals"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1021\/jm051197e","article-title":"MolDock: A new technique for high-accuracy molecular docking","volume":"49","author":"Thomsen","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/S0969-2126(98)00104-X","article-title":"The crystal structure of the Leishmania major surface proteinase leishmanolysin (gp63)","volume":"6","author":"Schlagenhauf","year":"1998","journal-title":"Structure."},{"key":"ref_32","first-page":"699","article-title":"On the law of entropy increasing of a one-dimensional infinite system II","volume":"34","author":"Niwa","year":"1994","journal-title":"J. Math. Kyoto Univ."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"104662","DOI":"10.1016\/j.bioorg.2021.104662","article-title":"Cathepsin K inhibitors based on 2-amino-1,3,4-oxadiazole derivatives","volume":"109","author":"Gontijo","year":"2021","journal-title":"Bioorg. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.3389\/fmicb.2019.01701","article-title":"Disarming Pseudomonas aeruginosa virulence by the inhibitory action of 1,10-phenanthroline-5,6-dione-based compounds: Elastase B (Lasb) as a chemotherapeutic target","volume":"10","author":"Galdino","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/0003-2697(80)90338-3","article-title":"Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates","volume":"102","author":"Heussen","year":"1980","journal-title":"Anal. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"819133","DOI":"10.3389\/fcimb.2021.819133","article-title":"The enhanced expression of cruzipain-like molecules in the phytoflagellate Phytomonas serpens recovered from the invertebrate and plant hosts","volume":"11","author":"Oliveira","year":"2022","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"12150","DOI":"10.1016\/S0021-9258(19)50320-9","article-title":"Sodium dodecyl sulfate-induced dissociation of complexes between human tissue plasminogen activator and its specific inhibitor","volume":"268","author":"Gaussem","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/elps.1150170113","article-title":"Assessing the stability of cystatin\/cysteine proteinase complexes using mildly-denaturing gelatin-polyacrylamide gel electrophoresis","volume":"17","author":"Michaud","year":"1996","journal-title":"Electrophoresis"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1590\/S0001-37652006000400006","article-title":"The ubiquitous gp63-like metalloprotease from lower trypanosomatids: In the search for a function","volume":"78","author":"Santos","year":"2006","journal-title":"An. Acad. Bras. Cienc."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"K\u00fchne, V., Rezaei, Z., Pitzinger, P., and B\u00fcscher, P. (2019). Systematic review on antigens for serodiagnosis of visceral leishmaniasis, with a focus on East Africa. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0007658"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"152085","DOI":"10.1016\/j.imbio.2021.152085","article-title":"Development of dominant epitope-based vaccines encoding Gp63, Kmp-11 and Amastin against visceral leishmaniasis","volume":"226","author":"Zhang","year":"2021","journal-title":"Immunobiology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3273","DOI":"10.1007\/s00436-021-07265-x","article-title":"Anti-Leishmania braziliensis activity of 1,10-phenanthroline-5,6-dione and its Cu(II) and Ag(I) complexes","volume":"120","author":"Lima","year":"2021","journal-title":"Parasitol. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.2174\/092986712800609788","article-title":"Antimicrobial action of chelating agents: Repercussions on the microorganism development, virulence and pathogenesis","volume":"19","author":"Santos","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.cbi.2006.08.025","article-title":"In vitro anti-tumour effect of 1,10-phenanthroline-5,6-dione (phendione), [Cu(phendione)3](ClO4)2.4H2O and [Ag(phendione)2]ClO4 using human epithelial cell lines","volume":"164","author":"Deegan","year":"2006","journal-title":"Chem. Biol. Interact."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.1038\/s41598-020-60263-4","article-title":"Effects of SDS on the activity and conformation of protein tyrosine phosphatase from Thermus thermophilus HB27","volume":"21","author":"Hou","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"307","DOI":"10.2174\/1389203724666230306153001","article-title":"Metallopeptidases as key virulence attributes of clinically relevant protozoa: New discoveries, perspectives, and frontiers of knowledge","volume":"24","author":"Santos","year":"2023","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4477","DOI":"10.1128\/IAI.67.9.4477-4484.1999","article-title":"Interaction of Leishmania gp63 with cellular receptors for fibronectin","volume":"67","author":"Brittingham","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1017\/S0031182018000367","article-title":"The role of metalloproteases in Leishmania species infection in the New World: A systematic review","volume":"145","author":"Murase","year":"2018","journal-title":"Parasitology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6272","DOI":"10.1128\/IAI.00853-05","article-title":"Role of host protein tyrosine phosphatase SHP-1 in Leishmania donovani-induced inhibition of nitric oxide production","volume":"74","author":"Forget","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.chom.2011.03.008","article-title":"Leishmania repression of host translation through mTOR cleavage is required for parasite survival and infection","volume":"9","author":"Jaramillo","year":"2011","journal-title":"Cell Host Microbe."}],"container-title":["Tropical Medicine and Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2414-6366\/8\/7\/348\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:03:30Z","timestamp":1760126610000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2414-6366\/8\/7\/348"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,30]]},"references-count":52,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["tropicalmed8070348"],"URL":"https:\/\/doi.org\/10.3390\/tropicalmed8070348","relation":{},"ISSN":["2414-6366"],"issn-type":[{"value":"2414-6366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,30]]}}}