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MAP1 and MAP2 are peptides with antimicrobial activity. Aiming to increase selectivity, enhance antimicrobial activity, and reduce its cytotoxicity, two bioconjugates (GVL1-MAP2 and GVL1-MAP1) with the guanidine derivative group in the N-terminus position were synthesized. Methods: The peptides and bioconjugates were synthesized by SPPS. The biological activity and inhibition of the CPB enzyme were evaluated. Results: Antileishmanial activity was evaluated, and the bioconjugates exhibited higher activity in both the promastigote and amastigote forms than isolated GVL1 and peptides alone. Discussion: GVL1-MAP2 bioconjugate demonstrated not only the greatest activity against L. amazonensis in the promastigote (IC50 = 3.2 \u03bcM) and amastigote (IC50 = 0.6 \u03bcM) forms but also prevented the parasite from infecting new host cells, reducing the infection rate by 3-fold compared to the untreated control. Similar results were obtained in L. infantum, with IC50 = 2.5 and 1.0 \u03bcM for promastigote and amastigote forms, respectively. In active serum, GVL1-MAP2 continued to show high activity. GVL1-MAP2 also showed bactericidal activity against most strains tested. The bioconjugate GVL1-MAP2 showed lower cytotoxicity than GVL1-MAP1 and amphotericin B in macrophages. Permeabilization studies and enzyme inhibition revealed that the peptide acts via at least two distinct mechanisms, with the primary mechanism targeting the membrane and inner targets as an inhibitor of the CPB enzyme. Conclusions: These data demonstrated that the synthesis of bioconjugates can be a tool for the development of bactericidal and antileishmanial compounds with improved potency and selectivity.<\/jats:p>","DOI":"10.3390\/ph19060835","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T14:36:56Z","timestamp":1779892616000},"page":"835","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Antileishmanial and Antibacterial Activity of Bioconjugate Guanidine\u2013Temporin"],"prefix":"10.3390","volume":"19","author":[{"given":"Gabriel Antunes","family":"Santoro","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Organic Chemistry, Institute of Chemistry, S\u00e3o Paulo State University (UNESP), Araraquara 14800-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7250-4908","authenticated-orcid":false,"given":"Natalia Caroline Souza","family":"Costa","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1109-0868","authenticated-orcid":false,"given":"Sarah Tolentino Rocha","family":"Brand\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Organic Chemistry, Institute of Chemistry, S\u00e3o Paulo State University (UNESP), Araraquara 14800-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4709-5487","authenticated-orcid":false,"given":"Jhonatan Santos","family":"de Lima","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5655-5449","authenticated-orcid":false,"given":"Angela Maria Arenas","family":"Velasquez","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2487-6176","authenticated-orcid":false,"given":"Luana Ribeiro","family":"dos Anjos","sequence":"additional","affiliation":[{"name":"School of Sciences and Technology, S\u00e3o Paulo State University (UNESP), Presidente Prudente 19060-080, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7817-6338","authenticated-orcid":false,"given":"Cau\u00e3 Dias","family":"Abr\u00e3o","sequence":"additional","affiliation":[{"name":"School of Sciences and Technology, S\u00e3o Paulo State University (UNESP), Presidente Prudente 19060-080, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Victor Marcelino","family":"de Souza","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Organic Chemistry, Institute of Chemistry, S\u00e3o Paulo State University (UNESP), Araraquara 14800-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3309-6937","authenticated-orcid":false,"given":"Marcela Nunes","family":"Argentin","sequence":"additional","affiliation":[{"name":"Department of Physics and Interdisciplinary Science, S\u00e3o Carlos Institute of Physics, University of S\u00e3o Paulo (USP), S\u00e3o Carlos 13563-120, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4489-1215","authenticated-orcid":false,"given":"Ilana Lopes Baratella da Cunha","family":"Camargo","sequence":"additional","affiliation":[{"name":"Department of Physics and Interdisciplinary Science, S\u00e3o Carlos Institute of Physics, University of S\u00e3o Paulo (USP), S\u00e3o Carlos 13563-120, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7280-3775","authenticated-orcid":false,"given":"Marcia A. 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Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1017\/S003118201600216X","article-title":"Leishmaniasis and Various Immunotherapeutic Approaches","volume":"145","author":"Taslimi","year":"2018","journal-title":"Parasitology"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ponte-Sucre, A., Gamarro, F., Dujardin, J.C., Barrett, M.P., L\u00f3pez-V\u00e9lez, R., Garc\u00eda-Hern\u00e1ndez, R., Pountain, A.W., Mwenechanya, R., and Papadopoulou, B. (2017). Drug Resistance and Treatment Failure in Leishmaniasis: A 21st Century Challenge. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0006052"},{"key":"ref_4","unstructured":"World Health Organization (2019). 2019 Antibacterial Agents in Clinical Development: An Analysis of the Antibacterial Clinical Development Pipeline, World Health Organization. Available online: https:\/\/iris.who.int\/server\/api\/core\/bitstreams\/945de890-a22e-47ee-95ae-610c9dc0250a\/content."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e51034","DOI":"10.15252\/embr.202051034","article-title":"Antibiotic Resistance and Persistence\u2014Implications for Human Health and Treatment Perspectives","volume":"21","author":"Huemer","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4385","DOI":"10.2147\/IDR.S514825","article-title":"Antimicrobial Peptides: Mechanisms, Applications, and Therapeutic Potential","volume":"18","author":"Alzain","year":"2025","journal-title":"Infect. Drug Resist."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"de Souza, J.V.M., Costa, N.C.S., Brasil, M.C.O.A., dos Anjos, L.R., de Menezes, R.P.B., Zampieri, E.H., de Lima, J.S., Velasquez, A.M.A., Scotti, L., and Scotti, M.T. (2025). Guanidines Conjugated with Cell-Penetrating Peptides: A New Approach for the Development of Antileishmanial Molecules. Molecules, 30.","DOI":"10.3390\/molecules30020264"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"da Silva Sanches, P.R., Sanchez-Velazquez, R., Batista, M.N., Carneiro, B.M., Bittar, C., De Lorenzo, G., Rahal, P., Patel, A.H., and Cilli, E.M. (2023). Antiviral Evaluation of New Synthetic Bioconjugates Based on GA-Hecate: A New Class of Antivirals Targeting Different Steps of Zika Virus Replication. Molecules, 28.","DOI":"10.3390\/molecules28134884"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-0773.1955.tb02972.x","article-title":"Guanidines and Oxidative Phosphorylations","volume":"11","author":"Hollunger","year":"1955","journal-title":"Acta Pharmacol. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6794","DOI":"10.4049\/jimmunol.161.12.6794","article-title":"Leishmania Mexicana Cysteine Proteinase-Deficient Mutants Have Attenuated Virulence for Mice and Potentiate a Th1 Response1","volume":"161","author":"Alexander","year":"1998","journal-title":"J. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"34008","DOI":"10.1021\/acsomega.3c04878","article-title":"Development of New Leishmanicidal Compounds via Bioconjugation of Antimicrobial Peptides and Antileishmanial Guanidines","volume":"8","author":"Costa","year":"2023","journal-title":"ACS Omega"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/cbdd.14052","article-title":"Synthetic Peptides Bioinspired in Temporin-PTa with Antibacterial and Antibiofilm Activity","volume":"100","author":"Ferreira","year":"2022","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1021\/bi00897a032","article-title":"Solid Phase Peptide Synthesis. III. An Improved Synthesis of Bradykinin","volume":"3","author":"Merrifield","year":"1964","journal-title":"Biochemistry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1086\/381972","article-title":"Clinical Relevance of Bacteriostatic versus Bactericidal Mechanisms of Action in the Treatment of Gram-Positive Bacterial Infections","volume":"38","author":"Pankey","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1016\/j.bbamem.2012.02.009","article-title":"Determining the Mechanism of Membrane Permeabilizing Peptides: Identification of Potent, Equilibrium Pore-Formers","volume":"1818","author":"Krauson","year":"2012","journal-title":"Biochim. Et Biophys. Acta (BBA) Biomembr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8393","DOI":"10.1039\/C5OB00563A","article-title":"Leishmania Cell Wall as a Potent Target for Antiparasitic Drugs. A Focus on the Glycoconjugates","volume":"13","author":"Cabezas","year":"2015","journal-title":"Org. Biomol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"dos Santos, M.G., Muxel, S.M., Zampieri, R.A., Pomorski, T.G., and Floeter-Winter, L.M. (2013). Transbilayer Dynamics of Phospholipids in the Plasma Membrane of the Leishmania Genus. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055604"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.bbamem.2006.07.003","article-title":"Interaction of Sitamaquine with Membrane Lipids of Leishmania Donovani Promastigotes","volume":"1768","author":"Loiseau","year":"2007","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Baileyid, F., Mondragon-Shem, K., Haines, L.R., Olabi, A., Alorfi, A., Ruiz-Postigo, J.A., Alvar, J., Hotez, P., Adams, E.R., and V\u00e9lez, I.D. (2019). Cutaneous Leishmaniasis and Co-Morbid Major Depressive Disorder: A Systematic Review with Burden Estimates. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007092"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/nrd4683","article-title":"Hit and Lead Criteria in Drug Discovery for Infectious Diseases of the Developing World","volume":"14","author":"Katsuno","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10","DOI":"10.4161\/hv.7.0.14556","article-title":"Vaccines for Leishmaniasis: From Proteome to Vaccine Candidates","volume":"7","author":"Schroeder","year":"2011","journal-title":"Hum. Vaccin."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s12602-022-09915-7","article-title":"Serum Stable and Low Hemolytic Temporin-SHa Peptide Analogs Disrupt Cell Membrane of Methicillin-Resistant Staphylococcus Aureus (MRSA)","volume":"14","author":"Maharjan","year":"2022","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.3390\/molecules20022775","article-title":"The Role of Phosphoglycans in the Susceptibility of Leishmania Mexicana to the Temporin Family of Anti-Microbial Peptides","volume":"20","author":"Eggimann","year":"2015","journal-title":"Molecules"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Silva, P.S.e., Guindo, A.S., Oliveira, P.H.C., de Moraes, L.F.R.N., Boleti, A.P.d.A., Ferreira, M.A., de Oliveira, C.F.R., Macedo, M.L.R., Rossato, L., and Simionatto, S. (2023). Evaluation of the Synthetic Multifunctional Peptide Hp-MAP3 Derivative of Temporin-PTa. Toxins, 15.","DOI":"10.3390\/toxins15010042"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Raja, Z., Andr\u00e9, S., Abbassi, F., Humblot, V., Lequin, O., Bouceba, T., Correia, I., Casale, S., Foulon, T., and Sereno, D. (2017). Insight into the Mechanism of Action of Temporin-SHa, a New Broad-Spectrum Antiparasitic and Antibacterial Agent. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0174024"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27394","DOI":"10.1038\/srep27394","article-title":"Design of an \u03b1-Helical Antimicrobial Peptide with Improved Cell-Selective and Potent Anti-Biofilm Activity","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1146\/annurev.mi.46.100192.000433","article-title":"The Lipophosphogl Yean of Leislfmania Parasites","volume":"46","author":"Turco","year":"1992","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1042\/bj2940305","article-title":"The Structure, Biosynthesis and Function of Glycosylated Phosphatidylinositols in the Parasitic Protozoa and Higher Eukaryotes","volume":"294","author":"McConville","year":"1993","journal-title":"Biochem. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.molbiopara.2009.12.004","article-title":"Phospholipid and Sphingolipid Metabolism in Leishmania","volume":"170","author":"Zhang","year":"2010","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1071\/CH19449","article-title":"The Mechanism of Membrane Permeabilization by Peptides: Still an Enigma","volume":"73","author":"Wimley","year":"2020","journal-title":"Aust. J. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14329","DOI":"10.1038\/s41598-018-32176-w","article-title":"GA-Hecate Antiviral Properties on HCV Whole Cycle Represent a New Antiviral Class and Open the Door for the Development of Broad Spectrum Antivirals","volume":"8","author":"Batista","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Gagat, P., Ostr\u00f3wka, M., Duda-Madej, A., and Mackiewicz, P. (2024). Enhancing Antimicrobial Peptide Activity through Modifications of Charge, Hydrophobicity, and Structure. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251910821"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.2174\/138161210793292555","article-title":"Chemical Modifications Designed to Improve Peptide Stability: Incorporation of Non-Natural Amino Acids, Pseudo-Peptide Bonds, and Cyclization","volume":"16","author":"Gentilucci","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mahlapuu, M., H\u00e5kansson, J., Ringstad, L., and Bj\u00f6rn, C. (2016). Antimicrobial Peptides: An Emerging Category of Therapeutic Agents. Front. Cell. Infect. Microbiol., 6.","DOI":"10.3389\/fcimb.2016.00194"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9603","DOI":"10.1007\/s00210-024-03318-x","article-title":"The Challenge of Antimicrobial Resistance (AMR): Current Status and Future Prospects","volume":"397","author":"Ferrara","year":"2024","journal-title":"Naunyn. Schmiedebergs. Arch. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Salam, M.A., Al-Amin, M.Y., Salam, M.T., Pawar, J.S., Akhter, N., Rabaan, A.A., and Alqumber, M.A.A. (2023). Antimicrobial Resistance: A Growing Serious Threat for Global Public Health. Healthcare, 11.","DOI":"10.20944\/preprints202305.0555.v1"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3903","DOI":"10.2147\/IDR.S234610","article-title":"Antimicrobial Resistance: Implications and Costs","volume":"12","author":"Dadgostar","year":"2019","journal-title":"Infect. Drug Resist."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"199","DOI":"10.2217\/fmb-2021-0133","article-title":"Leishmania and Its Relationships with Bacteria","volume":"17","author":"Brocchi","year":"2022","journal-title":"Future Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"361058","DOI":"10.1155\/2014\/361058","article-title":"Bacterial Sepsis in Patients with Visceral Leishmaniasis in Northwest Ethiopia","volume":"2014","author":"Endris","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ejmech.2019.03.032","article-title":"N,N\u2032,N\u2033-Trisubstituted Guanidines: Synthesis, Characterization and Evaluation of Their Leishmanicidal Activity","volume":"171","author":"Passianoto","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.imlet.2019.10.004","article-title":"Site Specific Microbiome of Leishmania Parasite and Its Cross-Talk with Immune Milieu","volume":"216","author":"Misra","year":"2019","journal-title":"Immunol. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1111\/cbdd.13840","article-title":"Designing a Leucine-Rich Antibacterial Nonapeptide with Potent Activity against Mupirocin-Resistant MRSA via a Structure\u2013Activity Relationship Study","volume":"97","author":"Ang","year":"2021","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Raheem, N., and Straus, S.K. (2019). Mechanisms of Action for Antimicrobial Peptides With Antibacterial and Antibiofilm Functions. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.02866"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1186\/s40001-022-00804-x","article-title":"The Effect of Nisin on the Biofilm Production, Antimicrobial Susceptibility and Biofilm Formation of Staphylococcus Aureus and Pseudomonas Aeruginosa","volume":"27","author":"Ghapanvari","year":"2022","journal-title":"Eur. J. Med. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"173","DOI":"10.52601\/bpr.2021.200037","article-title":"Latest Developments on the Mechanism of Action of Membrane Disrupting Peptides","volume":"7","author":"Pandidan","year":"2021","journal-title":"Biophys. Rep."},{"key":"ref_46","first-page":"3919","article-title":"The Antimicrobial Peptides and Their Potential Clinical Applications","volume":"11","author":"Lei","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11856","DOI":"10.1021\/bi980539y","article-title":"Relationship of Membrane Curvature to the Formation of Pores by Magainin 2","volume":"37","author":"Matsuzaki","year":"1998","journal-title":"Biochemistry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.4049\/jimmunol.173.5.3297","article-title":"Inhibition of Lipopolysaccharide-Induced Macrophage IL-12 Production by Leishmania Mexicana Amastigotes: The Role of Cysteine Peptidases and the NF-\u039aB Signaling Pathway1","volume":"173","author":"Cameron","year":"2004","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.4049\/jimmunol.170.4.1746","article-title":"The Leishmania Mexicana Cysteine Protease, CPB2.8, Induces Potent Th2 Responses","volume":"170","author":"Pollock","year":"2003","journal-title":"J. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.mib.2004.06.010","article-title":"Cysteine Peptidases as Virulence Factors of Leishmania","volume":"7","author":"Mottram","year":"2004","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Moreira, D., Rodrigues, V., Abengozar, M., Rivas, L., Rial, E., Laforge, M., Li, X., Foretz, M., Viollet, B., and Estaquier, J. (2015). Leishmania Infantum Modulates Host Macrophage Mitochondrial Metabolism by Hijacking the SIRT1-AMPK Axis. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004684"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Moreira, V.P., da Silva Mela, M.F., dos Anjos, L.R., Saraiva, L.F., Arenas Vel\u00e1squez, A.M., Kalaba, P., Fabisikov\u00e1, A., Clementino, L.d.C., Aufy, M., and Studenik, C. (2022). Novel Selective and Low-Toxic Inhibitor of LmCPB2.8\u0394CTE (CPB) One Important Cysteine Protease for Leishmania Virulence. Biomolecules, 12.","DOI":"10.3390\/biom12121903"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1046\/j.1523-1747.2003.12132.x","article-title":"Antimicrobial and Protease Inhibitory Functions of the Human Cathelicidin (HCAP18\/LL-37) Prosequence","volume":"120","author":"Zaiou","year":"2003","journal-title":"J. Investig. Dermatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4035","DOI":"10.1242\/jcs.113.22.4035","article-title":"Processing and Trafficking of Cysteine Proteases in Leishmania Mexicana","volume":"113","author":"Brooks","year":"2000","journal-title":"J. Cell Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.exppara.2004.03.005","article-title":"Leishmania Tropica: Cysteine Proteases Are Essential for Growth and Pathogenicity","volume":"106","author":"McKerrow","year":"2004","journal-title":"Exp. Parasitol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"126784","DOI":"10.1016\/j.micres.2021.126784","article-title":"Cysteine Proteases: Battling Pathogenic Parasitic Protozoans with Omnipresent Enzymes","volume":"249","author":"Rawat","year":"2021","journal-title":"Microbiol. Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Carneiro, P.P., Concei\u00e7\u00e3o, J., Macedo, M., Magalh\u00e3es, V., Carvalho, E.M., and Bacellar, O. (2016). The Role of Nitric Oxide and Reactive Oxygen Species in the Killing of Leishmania Braziliensis by Monocytes from Patients with Cutaneous Leishmaniasis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148084"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3704","DOI":"10.1111\/j.1432-1033.2004.04311.x","article-title":"Differences in Substrate Specificities between Cysteine Protease CPB Isoforms of Leishmania Mexicana Are Mediated by a Few Amino Acid Changes","volume":"271","author":"Juliano","year":"2004","journal-title":"Eur. J. Biochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1248\/cpb.c25-00272","article-title":"Development of Cell-Penetrating Peptides and Their Application to DDS","volume":"73","author":"Oba","year":"2025","journal-title":"Chem. Pharm. Bull."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Almeida, F.S., Moreira, V.P., Silva, E.d.S., Cardoso, L.L., de Sousa Palmeira, P.H., Cavalcante-Silva, L.H.A., de Ara\u00fajo, D.A.M., do Amaral, I.P.G., Gonz\u00e1lez, E.R.P., and Keesen, T.S.L. (2023). Leishmanicidal Activity of Guanidine Derivatives against Leishmania Infantum. Trop. Med. Infect. Dis., 8.","DOI":"10.3390\/tropicalmed8030141"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s12639-013-0377-3","article-title":"In Vitro Antileishmanial Activity of Methanolic and Aqueous Extracts of Eucalyptus Camaldulensis against Leishmania Major","volume":"39","author":"Nosratabadi","year":"2015","journal-title":"J. Parasit. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e00688-17","DOI":"10.1128\/AAC.00688-17","article-title":"Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1B","volume":"61","author":"Venn","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_63","unstructured":"Clinical and Laboratory Standards Institute (2013). Performance Standards for Antimicrobial Susceptibility Testing; CLSI Document M100, CLSI."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1007\/s00726-014-1832-x","article-title":"Interaction between the Antimicrobial Peptide Aurein 1.2 Dimer and Mannans","volume":"46","author":"Piccoli","year":"2014","journal-title":"Amino Acids"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.biopha.2017.08.096","article-title":"In Vivo Antileishmanial Activity and Histopathological Evaluation in Leishmania Infantum Infected Hamsters after Treatment with a Furoxan Derivative","volume":"95","author":"Passalacqua","year":"2017","journal-title":"Biomed. Pharmacother."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/6\/835\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T14:43:37Z","timestamp":1779893017000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/6\/835"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,27]]},"references-count":65,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ph19060835"],"URL":"https:\/\/doi.org\/10.3390\/ph19060835","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,27]]}}}