{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T07:13:41Z","timestamp":1785827621261,"version":"3.56.0"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T00:00:00Z","timestamp":1730332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Chem."],"abstract":"<jats:p>The lack of vaccines shows the need for alternative leishmaniasis treatments. <jats:italic>In vitro<\/jats:italic> study previously demonstrated the leishmanicidal activity of <jats:italic>A. nitidum<\/jats:italic> extracts. This study describes for the first time, the antileishmanial activity of <jats:italic>A. nitidum<\/jats:italic> extracts in infected Balb\/c mice and its immunomodulatory effect. The extract (EE) was obtained by maceration of the peel powder with ethanol, which was fractionated by acid-base partition, originating the alkaloid (FA) and neutral (FN) fractions. EE and FA were analyzed using mass spectroscopy. Daily intragastric treatment was performed with EE and FA, at doses of 200\u00a0mg\/kg and 400\u00a0mg\/kg, in Balb\/c mice with 28\u00a0days of infection by <jats:italic>Leishmania amazonensis<\/jats:italic>. A thickness gauge was used to assess the progression of the lesion and the MTT method to determine the parasite load in the spleen. The quantification of IL-10 and IFN-\u03b3 was performed by ELISA. Analysis of the mass spectrum of EE indicated the presence of the alkaloids corynantheol and yohimbine, while in FA the alkaloid dihydrocorynantheol was identified. To elucidate the mode of interaction of these alkaloids with the TR protein, molecular target of antileishmanial drugs, we used molecular modeling approaches such as docking, molecular dynamics simulations and free energy affinity. Treatment with EE for 28\u00a0days at the highest dose tested, significantly reduced the size of the lesion. EE and FA after 28\u00a0days of treatment showed dose-dependent antileishmanial activity, which reduced the parasite load in the spleen of infected mice by 42.5% and 22.1%, respectively. Both EE and FA presented immunomodulatory effect, as they decreased IL-10 expression and increased IFN-y levels. The effectiveness of <jats:italic>A. nitidum<\/jats:italic> in the treatment of cutaneous leishmaniasis was proven in this study. The results obtained <jats:italic>in silico<\/jats:italic> demonstrated that the compounds are capable of interacting with the catalytic residues of the TR. The affinity energy results demonstrated that the complexes formed are favorable for enzymatic inhibition. The alkaloids present in the plant have demonstrated not only antileishmanial activity, but also the ability to modulate the host\u2019s immune response. These promising results open perspectives for developing more effective and comprehensive treatments against cutaneous leishmaniasis.<\/jats:p>","DOI":"10.3389\/fchem.2024.1492770","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T04:51:35Z","timestamp":1730350295000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Aspidosperma nitidum reduces parasite load and modulates cytokines in BALB\/c mice infected with Leishmania (Leishmania) amazonensis"],"prefix":"10.3389","volume":"12","author":[{"given":"Heliton Patrick Cordovil","family":"Br\u00edgido","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Everton Luiz Pompeu","family":"Varela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f4nio Rafael","family":"Quadros Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorddy","family":"Neves Cruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Correa-Barbosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Edson de Sousa","family":"Siqueira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian Kallahan Silva","family":"Chagas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey Moacir do Ros\u00e1rio","family":"Marinho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliane","family":"Almeida Carneiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rlia Regina","family":"Coelho-Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Perc\u00e1rio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria F\u00e2ni","family":"Dolabela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1016\/S0031-9422(00)83773-5","article-title":"The simple \u03b2-carboline alkaloids","volume":"19","author":"Allen","year":"1980","journal-title":"Phytochemistry"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e0004900","DOI":"10.1371\/journal.pntd.0004900","article-title":"Morinda citrifolia Linn. Reduces parasite load and modulates cytokines and extracellular matrix proteins in C57bl\/6 mice infected with leishmania (leishmania) amazonensis","volume":"10","author":"Almeida-Souza","year":"2016","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1016\/S0031-9422(00)82898-8","article-title":"Alkaloid studies\u2014LVIII","volume":"6","author":"Arndt","year":"1967","journal-title":"Phytochemistry"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1021\/jm900185q","article-title":"Molecular basis of antimony treatment in Leishmaniasis","volume":"52","author":"Baiocco","year":"2009","journal-title":"J. Med. Chem."},{"key":"B5","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1159\/000071138","article-title":"Efficacy of 8-bromoguanosine against murine cutaneous leishmaniasis induced with Leishmania amazonensis","volume":"49","author":"Bar\u00e3o","year":"2003","journal-title":"Chemotherapy"},{"key":"B6","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1006\/abbi.1995.1227","article-title":"Families and clans of serine peptidases","volume":"318","author":"Barrett","year":"1995","journal-title":"Arch. Biochem. Biophys."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.3390\/molecules25081924","article-title":"Targeting trypanothione reductase, a key enzyme in the redox trypanosomatid metabolism, to develop new drugs against leishmaniasis and trypanosomiases","volume":"25","author":"Battista","year":"2020","journal-title":"Molecules"},{"key":"B8","doi-asserted-by":"publisher","first-page":"5648","DOI":"10.1063\/1.464913","article-title":"Density-functional thermochemistry. III. The role of exact exchange","volume":"98","author":"Becke","year":"1993","journal-title":"J. Chem. Phys."},{"key":"B9","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/0305-1978(87)90019-6","article-title":"Indole alkaloid evolution in Aspidosperma","volume":"15","author":"Bolzani","year":"1987","journal-title":"Biochem. Syst. Ecol."},{"key":"B72","unstructured":"10.2305\/IUCN.UK.2019-2.RLTS.T145684962A145684964.en\u201cAspidosperma excelsum\u201d in The IUCN Red List of Threatened Species 2019: e.T145684962A1456849642019"},{"key":"B10","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.jep.2004.03.045","article-title":"A search for natural bioactive compounds in Bolivia through a multidisciplinary approach: Part VI. Evaluation of the antimalarial activity of plants used by Isoce\u00f1o-Guaran\u00ed Indians","volume":"93","author":"Bourdy","year":"2004","journal-title":"J. Ethnopharmacol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1590\/s0100-40422010000600026","article-title":"Qu\u00edmica e farmacologia de quimioter\u00e1picos antineopl\u00e1sicos derivados de plantas","volume":"33","author":"Brand\u00e3o","year":"2010","journal-title":"Quim. Nova"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1007\/s42452-020-03340-7","article-title":"Antileishmanial activity of annona species (annonaceae)","volume":"2","author":"Br\u00edgido","year":"2020","journal-title":"SN Appl. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"18283","DOI":"10.1038\/s41598-021-97637-1","article-title":"Evaluation of acute and subacute toxicity of ethanolic extract and fraction of alkaloids from bark of Aspidosperma nitidum in mice","volume":"11","author":"Br\u00edgido","year":"2021","journal-title":"Sci. Rep."},{"key":"B14","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.fitote.2015.04.004","article-title":"Isoquinoline alkaloids as prolyl oligopeptidase inhibitors","volume":"103","author":"Cahl\u00edkov\u00e1","year":"2015","journal-title":"Fitoterapia"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1177\/1934578x1300801110","article-title":"Alkaloids from cheiranthus fragrans and their acetylcholinesterase, butyrylcholinesterase and prolyl oligopeptidase activities","volume":"8","author":"Cahl\u00edkov\u00e1","year":"2013","journal-title":"Nat. Prod. Commun."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1002\/jcc.20290","article-title":"The Amber biomolecular simulation programs","volume":"26","author":"Case","year":"2005","journal-title":"J. Comput. Chem."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1016\/j.meegid.2012.03.017","article-title":"Wound healing genes and susceptibility to cutaneous leishmaniasis in Brazil","volume":"12","author":"Castellucci","year":"2012","journal-title":"Infect. Genet. Evol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1007\/s10616-015-9874-9","article-title":"Cytotoxicity, genotoxicity and mechanism of action (via gene expression analysis) of the indole alkaloid aspidospermine (antiparasitic) extracted from Aspidosperma polyneuron in HepG2 cells","volume":"68","author":"Coatti","year":"2016","journal-title":"Cytotechnology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"9620","DOI":"10.1021\/ja00074a030","article-title":"Application of RESP charges to calculate conformational energies, hydrogen bond energies, and free energies of solvation","volume":"115","author":"Cornell","year":"1993","journal-title":"J. Am. Chem. Soc."},{"key":"B20","doi-asserted-by":"publisher","first-page":"8029","DOI":"10.1016\/j.biomaterials.2011.07.021","article-title":"Accelerated healing of cutaneous leishmaniasis in non-healing BALB\/c mice using water soluble amphotericin B-polymethacrylic acid","volume":"32","author":"Corware","year":"2011","journal-title":"Biomaterials"},{"key":"B21","doi-asserted-by":"publisher","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle mesh Ewald: an N\u22c5log(N) method for Ewald sums in large systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem. Phys."},{"key":"B22","doi-asserted-by":"publisher","first-page":"785","DOI":"10.3390\/molecules24040785","article-title":"Flavopereirine\u2014an alkaloid derived from geissospermum vellosii\u2014presents leishmanicidal activity in vitro","volume":"24","author":"da Silva e Silva","year":"2019","journal-title":"Molecules"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1933","DOI":"10.1086\/652870","article-title":"Immunopathological studies of leishmania amazonensis infection in resistant and in susceptible mice","volume":"201","author":"De Oliveira Cardoso","year":"2010","journal-title":"J. Infect. Dis."},{"key":"B24","doi-asserted-by":"publisher","first-page":"8662","DOI":"10.1038\/s41598-022-12396-x","article-title":"Activity of alkaloids from Aspidosperma nitidum against leishmania (leishmania) amazonensis","volume":"12","author":"do Socorro Silva da Veiga","year":"2022","journal-title":"Sci. Rep."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e3000410","DOI":"10.1371\/journal.pbio.3000410","article-title":"The arrive guidelines 2.0: updated guidelines for reporting animal research","volume":"18","author":"du Sert","year":"2020","journal-title":"PLoS Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1038\/nprot.2016.051","article-title":"Computational protein\u2013ligand docking and virtual drug screening with the AutoDock suite","volume":"11","author":"Forli","year":"2016","journal-title":"Nat. Protoc."},{"key":"B28","article-title":"Gaussian\u223c09 {R}evision {E}.01","author":"Frisch","year":"2024"},{"key":"B29","doi-asserted-by":"publisher","first-page":"25","DOI":"10.2147\/DDDT.S146521","article-title":"Leishmaniasis in humans: drug or vaccine therapy?","volume":"12","author":"Ghorbani","year":"2018","journal-title":"Drug Des. devel. Ther."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2645","DOI":"10.1038\/sj.jid.5700890","article-title":"TNF-\u03b1 suppresses \u03b1-smooth muscle actin expression in human dermal fibroblasts: an implication for abnormal wound healing","volume":"127","author":"Goldberg","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.idc.2012.03.001","article-title":"Cutaneous and mucocutaneous leishmaniasis","volume":"26","author":"Goto","year":"2012","journal-title":"Infect. Dis. Clin. North Am."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e1003699","DOI":"10.1371\/journal.ppat.1003699","article-title":"Deletion of IL-4 receptor alpha on dendritic cells renders BALB\/c mice hypersusceptible to leishmania major infection","volume":"9","author":"Hurdayal","year":"2013","journal-title":"PLoS Pathog."},{"key":"B33","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of simple potential functions for simulating liquid water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"key":"B34","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1016\/j.parint.2014.04.002","article-title":"A comparative evaluation of efficacy of chemotherapy, immunotherapy and immunochemotherapy in visceral leishmaniasis-an experimental study","volume":"63","author":"Joshi","year":"2014","journal-title":"Parasitol. Int."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.4049\/jimmunol.166.2.1141","article-title":"The role of IL-10 in promoting disease progression in leishmaniasis","volume":"166","author":"Kane","year":"2001","journal-title":"J. Immunol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1084\/jem.184.3.1127","article-title":"IL-4-deficient Balb\/c mice resist infection with Leishmania major","volume":"184","author":"Kopf","year":"1996","journal-title":"J. Exp. Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/S0169-4758(96)40010-2","article-title":"A simple method for quantifying Leishmania in tissues of infected animals","volume":"13","author":"Lima","year":"1997","journal-title":"Parasitol. Today"},{"key":"B39","doi-asserted-by":"publisher","first-page":"2090","DOI":"10.1063\/1.1332996","article-title":"Langevin stabilization of molecular dynamics","volume":"114","author":"Lzaguirre","year":"2001","journal-title":"J. Chem. Phys."},{"key":"B40","doi-asserted-by":"publisher","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"J. Chem. Theory Comput."},{"key":"B41","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1016\/0031-9422(95)00660-5","article-title":"Indole alkaloids from Aspidosperma ramiflorum","volume":"41","author":"Marques","year":"1996","journal-title":"Phytochemistry"},{"key":"B42","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1128\/AAC.02360-16","article-title":"Meglumine antimoniate (glucantime) causes oxidative stress-derived DNA damage in Balb\/c mice infected by leishmania (leishmania) infantum Antimicrob","volume":"61","author":"Moreira","year":"2017","journal-title":"Agents Chemother."},{"key":"B43","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"B44","doi-asserted-by":"publisher","first-page":"601","DOI":"10.4103\/0973-1296.160449","article-title":"Biological activities of Croton palanostigma Klotzsch","volume":"11","author":"Mota","year":"2015","journal-title":"Pharmacogn. Mag."},{"key":"B45","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1084\/jem.189.4.741","article-title":"Macrophage microbicidal mechanisms in vivo: reactive nitrogen versus oxygen intermediates in the killing of intracellular visceral Leishmania donovani","volume":"189","author":"Murray","year":"1999","journal-title":"J. Exp. Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.4269\/ajtmh.2006.74.1013","article-title":"Short report: responses to Leishmania donovani in mice deficient in both phagocyte oxidase and inducible nitric oxide synthase","volume":"74","author":"Murray","year":"2006","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"B47","doi-asserted-by":"publisher","first-page":"4950","DOI":"10.1128\/AAC.49.12.4950-4956.2005","article-title":"Efficacy of orally administered 2-substituted quinolines in experimental murine cutaneous and visceral leishmaniases","volume":"49","author":"Nakayama","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"B68","unstructured":"Guide for the care and use of laboratory animalsNational Academy Press1996"},{"key":"B48","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.actatropica.2011.02.007","article-title":"Systematic review of the adverse effects of cutaneous leishmaniasis treatment in the New World","volume":"118","author":"Oliveira","year":"2011","journal-title":"Acta Trop."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1852","DOI":"10.1038\/sj.jid.5701232","article-title":"IL-10 overexpression decreases inflammatory mediators and promotes regenerative healing in an adult model of scar formation","volume":"128","author":"Peranteau","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1590\/S0100-40422007000400037","article-title":"Alcal\u00f3ides ind\u00f3licos isolados de esp\u00e9cies do g\u00eanero Aspidosperma (Apocynaceae)","volume":"30","author":"Pereira","year":"2007","journal-title":"Quim. Nova"},{"key":"B51","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1093\/nar\/27.1.325","article-title":"MEROPS: the peptidase database","volume":"27","author":"Rawlings","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"B52","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","article-title":"Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes","volume":"23","author":"Ryckaert","year":"1977","journal-title":"J. Comput. Phys."},{"key":"B53","doi-asserted-by":"publisher","first-page":"15551","DOI":"10.1073\/pnas.0505630102","article-title":"The wound repair response controls outcome to cutaneous leishmaniasis","volume":"102","author":"Sakthianandeswaren","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B54","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1046\/j.1365-3156.1999.00491.x","article-title":"Treatment of two patients with diffuse cutaneous leishmaniasis caused by Leishmania mexicana modifies the immunohistological profile but not the disease outcome","volume":"4","author":"Salaiza-Suazo","year":"1999","journal-title":"Trop. Med. Int. Heal."},{"key":"B55","doi-asserted-by":"publisher","first-page":"2","DOI":"10.2174\/1573406418666220713145446","article-title":"Promising molecular targets related to polyamine biosynthesis in drug discovery against leishmaniasis","volume":"19","author":"Santiago-Silva","year":"2023","journal-title":"Med. Chem."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.3390\/molecules28031035","article-title":"Galantamine based novel acetylcholinesterase enzyme inhibitors: a molecular modeling design approach","volume":"28","author":"Silva","year":"2023","journal-title":"Molecules"},{"key":"B57","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1590\/S0074-02762004000300001","article-title":"Clinical and immunopathological spectrum of american cutaneous leishmaniasis with special reference to the disease in Amazonian Brazil - a review","volume":"99","author":"Silveira","year":"2004","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"B58","doi-asserted-by":"publisher","first-page":"2298","DOI":"10.1002\/ejoc.201300097","article-title":"Synthesis of (+)\u2010Centrolobine and its analogues by using acyl anion Chemistry","volume":"2013","author":"Sudarshan","year":"2013","journal-title":"Eur. J. Org. Chem."},{"key":"B59","doi-asserted-by":"publisher","first-page":"e202400380","DOI":"10.1002\/asia.202400380","article-title":"Recent advances in the synthesis of diarylheptanoids","volume":"19","author":"Sudarshan","year":"2024","journal-title":"Chemistry\u2013An Asian J."},{"key":"B60","doi-asserted-by":"publisher","first-page":"22035","DOI":"10.1039\/c4cp03179b","article-title":"Assessing the performance of MM\/PBSA and MM\/GBSA methods. 5. Improved docking performance using high solute dielectric constant MM\/GBSA and MM\/PBSA rescoring","volume":"16","author":"Sun","year":"2014","journal-title":"Phys. Chem. Chem. Phys."},{"key":"B61","doi-asserted-by":"publisher","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":"B62","doi-asserted-by":"publisher","first-page":"e525","DOI":"10.1016\/j.ijid.2011.03.021","article-title":"Recent advances in leishmaniasis treatment","volume":"15","author":"Tiuman","year":"2011","journal-title":"Int. J. Infect. Dis."},{"key":"B63","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1017\/S0031182016002523","article-title":"Chemotherapy of leishmaniasis: present challenges","volume":"145","author":"Uliana","year":"2018","journal-title":"Parasitology"},{"key":"B64","doi-asserted-by":"publisher","first-page":"e50210212646","DOI":"10.33448\/rsd-v10i2.12646","article-title":"Atividade leishmanicida de Aspidosperma nitidum Benth. Ex M\u00fcll. Arg","volume":"10","author":"Veiga","year":"2021","journal-title":"Res. Soc. Dev."},{"key":"B70","article-title":"Antileishmania activity of amazon plants. Master\u2019s Dissertation","author":"Veiga","year":"2013"},{"key":"B65","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1002\/jcc.20035","article-title":"Development and testing of a general Amber force field","volume":"25","author":"Wang","year":"2004","journal-title":"J. Comput. Chem."},{"key":"B66","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1021\/ja00860a023","article-title":"Biosynthesis of indole alkaloids. The Aspidosperma and iboga bases","volume":"84","author":"Wenkert","year":"1962","journal-title":"J. Am. Chem. Soc."},{"key":"B67","unstructured":"Leishmaniasis2023"}],"container-title":["Frontiers in Chemistry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fchem.2024.1492770\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T04:51:38Z","timestamp":1730350298000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fchem.2024.1492770\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,31]]},"references-count":68,"alternative-id":["10.3389\/fchem.2024.1492770"],"URL":"https:\/\/doi.org\/10.3389\/fchem.2024.1492770","relation":{},"ISSN":["2296-2646"],"issn-type":[{"value":"2296-2646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,31]]},"article-number":"1492770"}}