{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T13:50:50Z","timestamp":1768744250150,"version":"3.49.0"},"reference-count":113,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["CIRCNA\/BRB\/0281\/2019"],"award-info":[{"award-number":["CIRCNA\/BRB\/0281\/2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Peptide-based drugs are an attractive class of therapeutic agents, recently recognized by the pharmaceutical industry. These molecules are currently being used in the development of innovative therapies for diverse health conditions, including tropical diseases such as leishmaniasis. Despite its socioeconomic influence on public health, leishmaniasis remains long-neglected and categorized as a poverty-related disease, with limited treatment options. Peptides with antileishmanial effects encountered to date are a structurally heterogeneous group, which can be found in different natural sources\u2014amphibians, reptiles, insects, bacteria, marine organisms, mammals, plants, and others\u2014or inspired by natural toxins or proteins. This review details the biochemical and structural characteristics of over one hundred peptides and their potential use as molecular frameworks for the design of antileishmanial drug leads. Additionally, we detail the main chemical modifications or substitutions of amino acid residues carried out in the peptide sequence, and their implications in the development of antileishmanial candidates for clinical trials. Our bibliographic research highlights that the action of leishmanicidal peptides has been evaluated mainly using in vitro assays, with a special emphasis on the promastigote stage. In light of these findings, and considering the advances in the successful application of peptides in leishmaniasis chemotherapy, possible approaches and future directions are discussed here.<\/jats:p>","DOI":"10.3390\/ijms22094400","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T13:59:14Z","timestamp":1619099954000},"page":"4400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Peptides to Tackle Leishmaniasis: Current Status and Future Directions"],"prefix":"10.3390","volume":"22","author":[{"given":"Alberto A.","family":"Robles-Loaiza","sequence":"first","affiliation":[{"name":"Biomolecules Discovery Group, Universidad Regional Amaz\u00f3nica Ikiam, Tena 150150, Ecuador"}]},{"given":"Edgar A.","family":"Pinos-Tamayo","sequence":"additional","affiliation":[{"name":"Biomolecules Discovery Group, Universidad Regional Amaz\u00f3nica Ikiam, Tena 150150, Ecuador"}]},{"given":"Bruno","family":"Mendes","sequence":"additional","affiliation":[{"name":"Departamento de Biologia Animal, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-862, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9506-3781","authenticated-orcid":false,"given":"C\u00e1tia","family":"Teixeira","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5996-2621","authenticated-orcid":false,"given":"Cl\u00e1udia","family":"Alves","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6018-4724","authenticated-orcid":false,"given":"Paula","family":"Gomes","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4637-4468","authenticated-orcid":false,"given":"Jos\u00e9 R.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Biomolecules Discovery Group, Universidad Regional Amaz\u00f3nica Ikiam, Tena 150150, Ecuador"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,22]]},"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","unstructured":"Matlashewski, G., Pandey, R., Das, V., and Das, P. (2013). One more death from visceral leishmaniasis has gone by unnoticed. What can be done?. PLoS Negl. Trop. Dis., 7.","DOI":"10.1371\/journal.pntd.0002082"},{"key":"ref_3","unstructured":"WHO (2021, January 28). Leishmaniasis. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/leishmaniasis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hewawasam, C., Weerakoon, H.S., Thilakan, V., Lelwala, T., Prasanka, K., Rathnayaka, A.S., Gamage, S., and Agampodi, S. (2020). Is leishmaniasis adequately notified in Sri Lanka? A survey among doctors from an endemic district, Sri Lanka. BMC Public Health, 20.","DOI":"10.1186\/s12889-020-09066-w"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13071-017-2028-5","article-title":"The history of leishmaniasis","volume":"10","author":"Steverding","year":"2017","journal-title":"Parasites Vectors"},{"key":"ref_6","unstructured":"Melby, P., Travi, B., and Osorio, E.Y. (2019). Leishmania.. Encyclopedia of Microbiology, Elsevier."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.mib.2010.05.008","article-title":"Flagellum assembly and function during the Leishmania life cycle","volume":"13","author":"Gluenz","year":"2010","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1136\/pgmj.2006.047340corr1","article-title":"Leishmaniasis","volume":"83","author":"Piscopo","year":"2007","journal-title":"Postgrad. Med. J."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Alvar, J., and Arana, B.I. (2017). Appraisal of Leishmaniasis Chemotherapy, Current Status and Pipeline StrategiesChapter 1 Leishmaniasis, Impact and Therapeutic Needs. Drug Discovery for Leishmaniasis.","DOI":"10.1039\/9781788010177-00001"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"32376","DOI":"10.1039\/C5RA02669E","article-title":"Antileishmanial drug discovery: Comprehensive review of the last 10 years","volume":"5","author":"Sangshetti","year":"2015","journal-title":"Rsc. Adv."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez, O.L., Diaz-Toro, Y., Ovalle, C., Valderrama, L., Muvdi, S., Rodr\u00edguez, I., Gomez, M.A., and Saravia, N.G. (2014). Miltefosine and antimonial drug susceptibility of Leishmania Viannia species and populations in regions of high transmission in Colombia. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0002871"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10369","DOI":"10.1021\/cr400552x","article-title":"Fruitful decade for antileishmanial compounds from 2002 to late 2011","volume":"114","author":"Hussain","year":"2014","journal-title":"Chem. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/21678707.2019.1552853","article-title":"Leishmaniasis: Treatment, drug resistance and emerging therapies","volume":"7","author":"Sundar","year":"2019","journal-title":"Expert Opin. Orphan Drugs"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1080\/14787210.2018.1483720","article-title":"Prospects for antimicrobial peptide-based immunotherapy approaches in Leishmania control","volume":"16","author":"Zahedifard","year":"2018","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4231","DOI":"10.2174\/0929867323666160909155222","article-title":"Peptide therapeutics and the pharmaceutical industry: Barriers encountered translating from the laboratory to patients","volume":"23","author":"Rafferty","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s12929-017-0328-x","article-title":"Evaluation of the use of therapeutic peptides for cancer treatment","volume":"24","author":"Marqus","year":"2017","journal-title":"J. Biomed. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/978-981-13-3588-4_15","article-title":"Clinical application of AMPs","volume":"1117","author":"Costa","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.ejmech.2018.02.055","article-title":"A novel synthetic peptide inspired on Lys49 phospholipase A2 from Crotalus oreganus abyssus snake venom active against multidrug-resistant clinical isolates","volume":"149","author":"Almeida","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_19","first-page":"868","article-title":"Antimicrobial peptides for leishmaniasis","volume":"11","author":"Cobb","year":"2010","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"ref_20","first-page":"5","article-title":"Peptides with dual antimicrobial and anticancer activities","volume":"5","author":"Silva","year":"2017","journal-title":"Front. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"294","DOI":"10.3389\/fmicb.2013.00294","article-title":"From antimicrobial to anticancer peptides. A review","volume":"4","author":"Gaspar","year":"2013","journal-title":"Front. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3389\/fcimb.2020.00105","article-title":"Antifungal Peptides as Therapeutic Agents","volume":"10","author":"Arbulu","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1002\/ddr.21456","article-title":"Harnessing snake venom phospholipases A2 to novel approaches for overcoming antibiotic resistance","volume":"80","author":"Almeida","year":"2019","journal-title":"Drug Dev. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"194","DOI":"10.3389\/fcimb.2016.00194","article-title":"Antimicrobial peptides: An emerging category of therapeutic agents","volume":"6","author":"Mahlapuu","year":"2016","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.2174\/138945012802002393","article-title":"Antimicrobial peptide action on parasites","volume":"13","author":"Torrent","year":"2012","journal-title":"Curr. Drug Targets"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1128\/AAC.02328-15","article-title":"Identification of synthetic and natural host defense peptides with leishmanicidal activity","volume":"60","author":"Marr","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Luque-Ortega, J.R., and Rivas, L. (2010). Characterization of the leishmanicidal activity of antimicrobial peptides. Antimicrobial Peptides, Springer.","DOI":"10.1007\/978-1-60761-594-1_25"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Torres-Guerrero, E., Quintanilla-Cedillo, M.R., Ruiz-Esmenjaud, J., and Arenas, R. (2017). Leishmaniasis: A review. F1000Research, 6.","DOI":"10.12688\/f1000research.11120.1"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Mehta, D., Anand, P., Kumar, V., Joshi, A., Mathur, D., Singh, S., Tuknait, A., Chaudhary, K., Gautam, S.K., and Gautam, A. (2014). ParaPep: A web resource for experimentally validated antiparasitic peptide sequences and their structures. Database.","DOI":"10.1093\/database\/bau051"},{"key":"ref_30","first-page":"414","article-title":"Functional and structural damage in Leishmania mexicana exposed to the cationic peptide dermaseptin","volume":"59","author":"Hernandez","year":"1992","journal-title":"Eur. J. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.resmic.2011.02.005","article-title":"Natural roles of antimicrobial peptides in microbes, plants and animals","volume":"162","author":"Kereszt","year":"2011","journal-title":"Res. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4610","DOI":"10.2174\/0929867323666160825162435","article-title":"Towards the development of synthetic antibiotics: Designs inspired by natural antimicrobial peptides","volume":"23","author":"Azmi","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/psc.2947","article-title":"Computational resources and tools for antimicrobial peptides","volume":"23","author":"Liu","year":"2017","journal-title":"J. Pept. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Haney, E.F., Mansour, S.C., and Hancock, R.E. (2017). Antimicrobial peptides: An introduction. Antimicrobial Peptides, Springer.","DOI":"10.1007\/978-1-4939-6737-7_1"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.2174\/138920111796117436","article-title":"Advances in methods for therapeutic peptide discovery, design and development","volume":"12","author":"Pirogova","year":"2011","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1074\/jbc.M410795200","article-title":"Temporins, small antimicrobial peptides with leishmanicidal activity","volume":"280","author":"Mangoni","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"8205","DOI":"10.1016\/j.bmc.2008.07.032","article-title":"Synthesis and antimicrobial activity of dermaseptin S1 analogues","volume":"16","author":"Savoia","year":"2008","journal-title":"Bioorgan. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1042\/bj3300453","article-title":"The plasma membrane of Leishmania donovani promastigotes is the main target for CA (1\u20138) M (1\u201318), a synthetic cecropin A\u2013melittin hybrid peptide","volume":"330","author":"Ubach","year":"1998","journal-title":"Biochem. J."},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1128\/AAC.45.9.2441-2449.2001","article-title":"N-terminal fatty acid substitution increases the leishmanicidal activity of CA (1\u20137) M (2\u20139), a cecropin-melittin hybrid peptide","volume":"45","author":"Chicharro","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1128\/AAC.48.8.2980-2986.2004","article-title":"Role of positional hydrophobicity in the leishmanicidal activity of magainin 2","volume":"48","author":"Guerrero","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"108612","DOI":"10.1016\/j.cbpc.2019.108612","article-title":"Potential use of 13-mer peptides based on phospholipase and oligoarginine as leishmanicidal agents","volume":"226","author":"Mendes","year":"2019","journal-title":"Comp. Biochem. Physiol. Part C Toxicol. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"718","DOI":"10.2174\/0929866527666200129152954","article-title":"Effect of isolated proteins from Crotalus durissus terrificus venom on Leishmania (Leishmania) amazonensis-infected macrophages","volume":"27","author":"Katz","year":"2020","journal-title":"Protein Pept. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.peptides.2010.10.009","article-title":"Evidence for convergent evolution in the antimicrobial peptide system in anuran amphibians","volume":"32","year":"2011","journal-title":"Peptides"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1016\/j.bbamem.2009.03.008","article-title":"The role of amphibian antimicrobial peptides in protection of amphibians from pathogens linked to global amphibian declines","volume":"1788","year":"2009","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"ftaa053","DOI":"10.1093\/femspd\/ftaa053","article-title":"Cruzioseptins, antibacterial peptides from Cruziohyla calcarifer skin, as promising leishmanicidal agents","volume":"78","author":"Mendes","year":"2020","journal-title":"Pathog. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Proa\u00f1o-Bola\u00f1os, C., Blasco-Z\u00fa\u00f1iga, A., Almeida, J.R., Wang, L., Llumiquinga, M.A., Rivera, M., Zhou, M., Chen, T., and Shaw, C. (2019). Unravelling the skin secretion peptides of the gliding leaf frog, Agalychnis spurrelli (Hylidae). Biomolecules, 9.","DOI":"10.3390\/biom9110667"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/0014-5793(96)00050-6","article-title":"Broad spectrum antibiotic activity of skin-PYY","volume":"380","author":"Vouldoukis","year":"1996","journal-title":"FEBS Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1002\/bip.22925","article-title":"Ocellatin-PT antimicrobial peptides: High-resolution microscopy studies in antileishmania models and interactions with mimetic membrane systems","volume":"105","author":"Oliveira","year":"2016","journal-title":"Biopolymers"},{"key":"ref_50","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_51","doi-asserted-by":"crossref","first-page":"881","DOI":"10.4269\/ajtmh.2008.79.881","article-title":"Identification of aerobic gut bacteria from the kala azar vector, Phlebotomus argentipes: A platform for potential paratransgenic manipulation of sand flies","volume":"79","author":"Hillesland","year":"2008","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"349","DOI":"10.35248\/2155-9597.1000349","article-title":"Dynamics and fitness cost of genetically engineered Entrobacter cloacae expressing defensin for paratransgenesis in Phlebotomus papatasi","volume":"10","author":"Abassi","year":"2019","journal-title":"J. Bacteriol. Parasitol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e02851","DOI":"10.7554\/eLife.02851","article-title":"Global distribution maps of the leishmaniases","volume":"3","author":"Pigott","year":"2014","journal-title":"Elife"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.biochi.2012.10.015","article-title":"Antibacterial and leishmanicidal activities of temporin-SHd, a 17-residue long membrane-damaging peptide","volume":"95","author":"Abbassi","year":"2013","journal-title":"Biochimie"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1093\/abbs\/gmz128","article-title":"In vitro leishmanicidal activity of antimicrobial peptide KDEL against Leishmania tarentolae","volume":"51","author":"Cao","year":"2019","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0166-6851(02)00300-6","article-title":"Induction of autophagic cell death in Leishmania donovani by antimicrobial peptides","volume":"127","author":"Bera","year":"2003","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Ron\u010devi\u0107, T., Puizina, J., and Tossi, A. (2019). Antimicrobial peptides as anti-infective agents in pre-post-antibiotic era?. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225713"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Browne, K., Chakraborty, S., Chen, R., Willcox, M.D., Black, D.S., Walsh, W.R., and Kumar, N. (2020). A new era of antibiotics: The clinical potential of antimicrobial peptides. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197047"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"aau5480","DOI":"10.1126\/science.aau5480","article-title":"Antimicrobial peptides: Application informed by evolution","volume":"368","author":"Lazzaro","year":"2020","journal-title":"Science"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Lynn, M.A., Kindrachuk, J., Marr, A.K., Jenssen, H., Pant\u00e9, N., Elliott, M.R., Napper, S., Hancock, R.E., and McMaster, W.R. (2011). Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: Role of leishmanolysin in parasite survival. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001141"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.peptides.2011.01.011","article-title":"Leishmanicidal activity of synthetic antimicrobial peptides in an infection model with human dendritic cells","volume":"32","author":"Lozano","year":"2011","journal-title":"Peptides"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1128\/AAC.48.2.641-643.2004","article-title":"Safety and efficacy of antimicrobial peptides against naturally acquired leishmaniasis","volume":"48","author":"Alberola","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1128\/AAC.01555-06","article-title":"Immunomodulatory peptide from cystatin, a natural cysteine protease inhibitor, against leishmaniasis as a model macrophage disease","volume":"51","author":"Mukherjee","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1128\/AAC.05349-11","article-title":"Efficacy of synthetic peptides RP-1 and AA-RP-1 against Leishmania species in vitro and in vivo","volume":"56","author":"Erfe","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6040","DOI":"10.4049\/jimmunol.1301921","article-title":"Protective role of the neuropeptide urocortin II against experimental sepsis and leishmaniasis by direct killing of pathogens","volume":"191","author":"Caro","year":"2013","journal-title":"J. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"14583","DOI":"10.1074\/jbc.M114.560573","article-title":"Therapeutic efficacy of stable analogues of vasoactive intestinal peptide against pathogens","volume":"289","author":"Cavazzuti","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Abdossamadi, Z., Seyed, N., Zahedifard, F., Taheri, T., Taslimi, Y., Montakhab-Yeganeh, H., Badirzadeh, A., Vasei, M., Gharibzadeh, S., and Rafati, S. (2017). Human Neutrophil Peptide 1 as immunotherapeutic agent against Leishmania infected BALB\/c mice. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0006123"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.2217\/fmb.12.85","article-title":"Modes of action of Leishmanicidal antimicrobial peptides","volume":"7","author":"Marr","year":"2012","journal-title":"Future Microbiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.2217\/imt-2017-0076","article-title":"Live Leishmania tarentolae secreting HNP1 as an immunotherapeutic tool against Leishmania infection in BALB\/c mice","volume":"9","author":"Abdossamadi","year":"2017","journal-title":"Immunotherapy"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.jconrel.2012.05.023","article-title":"Defeating Leishmania resistance to miltefosine (hexadecylphosphocholine) by peptide-mediated drug smuggling: A proof of mechanism for trypanosomatid chemotherapy","volume":"161","author":"Beatriz","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4213037","DOI":"10.1155\/2017\/4213037","article-title":"A synthetic strategy for conjugation of paromomycin to cell-penetrating TAT (48-60) for delivery and visualization into Leishmania parasites","volume":"2017","author":"Defaus","year":"2017","journal-title":"Int. J. Pept."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"D1087","DOI":"10.1093\/nar\/gkv1278","article-title":"APD3: The antimicrobial peptide database as a tool for research and education","volume":"44","author":"Wang","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Usmani, S.S., Bedi, G., Samuel, J.S., Singh, S., Kalra, S., Kumar, P., Ahuja, A.A., Sharma, M., Gautam, A., and Raghava, G.P. (2017). THPdb: Database of FDA-approved peptide and protein therapeutics. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181748"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"722","DOI":"10.2174\/0929866523666160530185137","article-title":"The amazing world of peptide engineering: The example of antimicrobial peptides from frogs and their analogues","volume":"23","author":"Guimaraes","year":"2016","journal-title":"Protein Pept. Lett."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.exppara.2018.11.006","article-title":"Investigation of the antimicrobial activity of a short cationic peptide against promastigote and amastigote forms of Leishmania major (MHRO\/IR\/75\/ER): An in vitro study","volume":"196","author":"Ebrahimzade","year":"2019","journal-title":"Exp. Parasitol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"107823","DOI":"10.1016\/j.exppara.2019.107823","article-title":"Comparative study of different forms of Jellein antimicrobial peptide on Leishmania parasite","volume":"209","author":"Zahedifard","year":"2020","journal-title":"Exp. Parasitol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1021\/mp8001039","article-title":"Kahalalide F, an antitumor depsipeptide in clinical trials, and its analogues as effective antileishmanial agents","volume":"6","author":"Cruz","year":"2009","journal-title":"Mol. Pharm."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"305","DOI":"10.2174\/1573407212666161014131415","article-title":"Antileishmanial and immunomodulatory effects of Dermaseptin-01, a promising peptide against Leishmania amazonensis","volume":"13","author":"Chaves","year":"2017","journal-title":"Curr. Bioact. Compd."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Haines, L.R., Thomas, J.M., Jackson, A.M., Eyford, B.A., Razavi, M., Watson, C.N., Gowen, B., Hancock, R.E., and Pearson, T.W. (2009). Killing of trypanosomatid parasites by a modified bovine host defense peptide, BMAP-18. PLoS Negl. Trop. Dis., 3.","DOI":"10.1371\/journal.pntd.0000373"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.exppara.2013.09.016","article-title":"Antimicrobial peptides isolated from Phyllomedusa nordestina (Amphibia) alter the permeability of plasma membrane of Leishmania and Trypanosoma cruzi","volume":"135","author":"Pinto","year":"2013","journal-title":"Exp. Parasitol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.exppara.2013.10.011","article-title":"Spinigerin induces apoptotic like cell death in a caspase independent manner in Leishmania donovani","volume":"135","author":"Sardar","year":"2013","journal-title":"Exp. Parasitol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.tibtech.2003.10.005","article-title":"Therapeutic peptides","volume":"21","author":"Lien","year":"2003","journal-title":"Trends Biotechnol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.exppara.2007.07.011","article-title":"Trypanocidal and leishmanicidal activities of different antimicrobial peptides (AMPs) isolated from aquatic animals","volume":"118","author":"Miletti","year":"2008","journal-title":"Exp. Parasitol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.exppara.2010.02.006","article-title":"Interactions of antimicrobial peptides with Leishmania and trypanosomes and their functional role in host parasitism","volume":"126","author":"McGwire","year":"2010","journal-title":"Exp. Parasitol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1099\/jmm.0.000258","article-title":"Comparative functional properties of engineered cationic antimicrobial peptides consisting exclusively of tryptophan and either lysine or arginine","volume":"65","author":"Deslouches","year":"2016","journal-title":"J. Med. Microbiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e23025","DOI":"10.1002\/bip.23025","article-title":"Lysine to arginine mutagenesis of chlorotoxin enhances its cellular uptake","volume":"108","author":"Ojeda","year":"2017","journal-title":"Pept. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1128\/AAC.00925-06","article-title":"Role of peptide hydrophobicity in the mechanism of action of \u03b1-helical antimicrobial peptides","volume":"51","author":"Chen","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Sabi\u00e1 J\u00fanior, E.F., Menezes, L.F.S., de Ara\u00fajo, I.F.S., and Schwartz, E.F. (2019). Natural occurrence in venomous arthropods of antimicrobial peptides active against protozoan parasites. Toxins, 11.","DOI":"10.3390\/toxins11100563"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1016\/j.peptides.2007.09.017","article-title":"Decoralin, a novel linear cationic \u03b1-helical peptide from the venom of the solitary eumenine wasp Oreumenes decoratus","volume":"28","author":"Konno","year":"2007","journal-title":"Peptides"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"55042","DOI":"10.1074\/jbc.M408881200","article-title":"Dissection of antibacterial and toxic activity of Melittin a leucine zipper motif plays a crucial role in determining its hemolytic activity but not antibacterial activity","volume":"279","author":"Asthana","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"10905","DOI":"10.1021\/bi9009874","article-title":"Design of nontoxic analogues of cathelicidin-derived bovine antimicrobial peptide BMAP-27: The role of leucine as well as phenylalanine zipper sequences in determining its toxicity","volume":"48","author":"Ahmad","year":"2009","journal-title":"Biochemistry"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/1097-0282(2000)55:1<4::AID-BIP30>3.0.CO;2-M","article-title":"Amphipathic, \u03b1-helical antimicrobial peptides","volume":"55","author":"Tossi","year":"2000","journal-title":"Pept. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.3390\/ph6121543","article-title":"Antimicrobial peptides","volume":"6","author":"Bahar","year":"2013","journal-title":"Pharmaceuticals"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1128\/AAC.49.6.2412-2420.2005","article-title":"Effects of acyl versus aminoacyl conjugation on the properties of antimicrobial peptides","volume":"49","author":"Radzishevsky","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1111\/j.1420-9101.2005.00925.x","article-title":"Molecular evolution of animal antimicrobial peptides: Widespread moderate positive selection","volume":"18","author":"Tennessen","year":"2005","journal-title":"J. Evol. Biol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Osorio, D., Rond\u00f3n-Villarrea, P., and Torres, R. (2015). Peptides: A package for data mining of antimicrobial peptides. R J., 7.","DOI":"10.32614\/RJ-2015-001"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Lee, H.-T., Lee, C.-C., Yang, J.-R., Lai, J.Z., and Chang, K.Y. (2015). A large-scale structural classification of antimicrobial peptides. Biomed. Res. Int.","DOI":"10.1155\/2015\/475062"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"D1094","DOI":"10.1093\/nar\/gkv1051","article-title":"CAMPR3: A database on sequences, structures and signatures of antimicrobial peptides","volume":"44","author":"Waghu","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Wang, C.-K., Shih, L.-Y., and Chang, K.Y. (2017). Large-scale analysis of antimicrobial activities in relation to amphipathicity and charge reveals novel characterization of antimicrobial peptides. Molecules, 22.","DOI":"10.3390\/molecules22112037"},{"key":"ref_100","unstructured":"PAHO (2021, January 28). Leishmaniasis. Available online: https:\/\/www.paho.org\/es\/temas\/leishmaniasis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3389\/fpubh.2020.00011","article-title":"The geographical distribution of cutaneous leishmaniasis causative agents in Iran and its neighboring countries, a review","volume":"8","author":"Ghatee","year":"2020","journal-title":"Front. Public Health"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1093\/intimm\/dxx075","article-title":"How to master the host immune system? Leishmania parasites have the solutions!","volume":"30","author":"Rossi","year":"2018","journal-title":"Int. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Boussoffara, T., Boubaker, M.S., Ahmed, M.B., Mokni, M., Guizani, I., Salah, A.B., and Louzir, H. (2019). Histological and immunological differences between zoonotic cutaneous leishmaniasis due to Leishmania major and sporadic cutaneous leishmaniasis due to Leishmania infantum. Parasite, 26.","DOI":"10.1051\/parasite\/2019007"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.drudis.2009.10.009","article-title":"Synthetic therapeutic peptides: Science and market","volume":"15","author":"Vlieghe","year":"2010","journal-title":"Drug Discov. Today"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1080\/10408363.2019.1631249","article-title":"Designing and optimizing new antimicrobial peptides: All targets are not the same","volume":"56","author":"Patarroyo","year":"2019","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ejmech.2017.04.020","article-title":"First example of peptides targeting the dimer interface of Leishmania infantum trypanothione reductase with potent in vitro antileishmanial activity","volume":"135","author":"Toro","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/s41564-018-0154-2","article-title":"Revising Leishmania\u2019s life cycle","volume":"3","author":"Bates","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"K\u00fcckelhaus, S.A., Aquino, D.S.A.d., Borges, T.K., Moreira, D.C., Leite, L.d.M., Muniz-Junqueira, M.I., K\u00fcckelhaus, C.S., Romero, G.A.S., Prates, M.V., and Bloch, C. (2020). Phylloseptin-1 is Leishmanicidal for Amastigotes of Leishmania amazonensis Inside Infected Macrophages. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17134856"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"581","DOI":"10.3201\/eid0404.980408","article-title":"Bacterial symbiosis in arthropods and the control of disease transmission","volume":"4","author":"Beard","year":"1998","journal-title":"Emerg. Infect. Dis."},{"key":"ref_110","unstructured":"WHO (2021, January 28). WHO Takes a Position on Genetically Modified Mosquitoes. Available online: https:\/\/www.who.int\/news\/item\/14-10-2020-who-takes-a-position-on-genetically-modified-mosquitoes."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.pt.2010.07.005","article-title":"Choosing anti-Plasmodium molecules for genetically modifying mosquitoes: Focus on peptides","volume":"26","author":"Carter","year":"2010","journal-title":"Trends Parasitol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"104260","DOI":"10.1016\/j.biocontrol.2020.104260","article-title":"Recent developments and future directions in the paratransgenesis based control of Leishmania transmission","volume":"145","author":"Wijerathna","year":"2020","journal-title":"Biol. Control"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/j.1365-2583.2010.01000.x","article-title":"Flying vaccinator; a transgenic mosquito delivers a Leishmania vaccine via blood feeding","volume":"19","author":"Yamamoto","year":"2010","journal-title":"Insect Mol. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/4400\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:51:37Z","timestamp":1760161897000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/4400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,22]]},"references-count":113,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["ijms22094400"],"URL":"https:\/\/doi.org\/10.3390\/ijms22094400","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,22]]}}}