{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:49:08Z","timestamp":1790758148919,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2019,12,11]],"date-time":"2019-12-11T00:00:00Z","timestamp":1576022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>With an estimated annual incidence of one million cases, leishmaniasis is one of the top five vector-borne diseases. Currently available medical treatments involve side effects, including toxicity, non-specific targeting, and resistance development. Thus, new antileishmanial chemical entities are of the utmost interest to fight against this disease. The aim of this study was to obtain potential antileishmanial natural products from Psidium guajava leaves using a metabolomic workflow. Several crude extracts from P. guajava leaves harvested from different locations in the Lao People\u2019s Democratic Republic (Lao PDR) were profiled by liquid chromatography coupled to high-resolution mass spectrometry, and subsequently evaluated for their antileishmanial activities. The putative active compounds were highlighted by multivariate correlation analysis between the antileishmanial response and chromatographic profiles of P. guajava mixtures. The results showed that the pooled apolar fractions from P. guajava were the most active (IC50 = 1.96 \u00b1 0.47 \u00b5g\/mL). Multivariate data analysis of the apolar fractions highlighted a family of triterpenoid compounds, including jacoumaric acid (IC50 = 1.318 \u00b1 0.59 \u00b5g\/mL) and corosolic acid (IC50 = 1.01 \u00b1 0.06 \u00b5g\/mL). Our approach allowed the identification of antileishmanial compounds from the crude extracts in only a small number of steps and can be easily adapted for use in the discovery workflows of several other natural products.<\/jats:p>","DOI":"10.3390\/molecules24244536","type":"journal-article","created":{"date-parts":[[2019,12,12]],"date-time":"2019-12-12T03:20:16Z","timestamp":1576120816000},"page":"4536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Antileishmanial Compounds Isolated from Psidium Guajava L. Using a Metabolomic Approach"],"prefix":"10.3390","volume":"24","author":[{"given":"Chiobouaphong","family":"Phakeovilay","sequence":"first","affiliation":[{"name":"UMR 152 Pharma Dev, Universit\u00e9 de Toulouse, IRD, UPS, 31000 Toulouse, France"},{"name":"Faculty of Pharmacy, University of Health Sciences, Ministry of Health, Vientiane 01000, Lao People\u2019s Democratic Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Bourgeade-Delmas","sequence":"additional","affiliation":[{"name":"UMR 152 Pharma Dev, Universit\u00e9 de Toulouse, IRD, UPS, 31000 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4413-2948","authenticated-orcid":false,"given":"Pierre","family":"Perio","sequence":"additional","affiliation":[{"name":"UMR 152 Pharma Dev, Universit\u00e9 de Toulouse, IRD, UPS, 31000 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Valentin","sequence":"additional","affiliation":[{"name":"UMR 152 Pharma Dev, Universit\u00e9 de Toulouse, IRD, UPS, 31000 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4179-7995","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Chassagne","sequence":"additional","affiliation":[{"name":"UMR 152 Pharma Dev, Universit\u00e9 de Toulouse, IRD, UPS, 31000 Toulouse, France"},{"name":"Center for the Study of Human Health, Emory University, 615 Michael Street, Whitehead Building, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Deharo","sequence":"additional","affiliation":[{"name":"UMR 152 Pharma Dev, Universit\u00e9 de Toulouse, IRD, UPS, 31000 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Reybier","sequence":"additional","affiliation":[{"name":"UMR 152 Pharma Dev, Universit\u00e9 de Toulouse, IRD, UPS, 31000 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6321-9005","authenticated-orcid":false,"given":"Guillaume","family":"Marti","sequence":"additional","affiliation":[{"name":"UMR 152 Pharma Dev, Universit\u00e9 de Toulouse, IRD, UPS, 31000 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,11]]},"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":"873","DOI":"10.1038\/nrmicro1748","article-title":"Visceral leishmaniasis: What are the needs for diagnosis, treatment and control?","volume":"5","author":"Chappuis","year":"2007","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.apjtm.2016.06.021","article-title":"Worldwide risk factors in leishmaniasis","volume":"9","author":"Oryan","year":"2016","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1016\/j.drudis.2017.06.004","article-title":"Leishmaniasis drug discovery: recent progress and challenges in assay development","volume":"22","author":"Zulfiqar","year":"2017","journal-title":"Drug Discov. Today"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"525","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":"ref_6","doi-asserted-by":"crossref","unstructured":"Jannin, J., Solano, P., Quick, I., and Debre, P. (2017). The francophone network on neglected tropical diseases. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005738"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s40262-017-0570-0","article-title":"Clinical pharmacokinetics of systemically administered antileishmanial drugs","volume":"57","author":"Kip","year":"2018","journal-title":"Clin. Pharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1590\/S0074-02762005000700019","article-title":"Antileishmanial and trypanocidal activity of Brazilian Cerrado plants","volume":"100","author":"Desrivot","year":"2005","journal-title":"Mem. Inst. Oswaldo Cruz. Rio De Janerio"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jep.2008.01.025","article-title":"Psidium guajava: A review of its traditional uses, phytochemistry and pharmacology","volume":"117","author":"Mitchell","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13002-019-0307-2","article-title":"Hmong herbal medicine and herbalists in Lao PDR: pharmacopeia and knowledge transmission","volume":"15","author":"Dubost","year":"2019","journal-title":"J. Ethnobiol. Ethnomed."},{"key":"ref_11","first-page":"156","article-title":"Pharmacognostic evaluation of Psidium guajava Linn. leaves (Mrytaceae)","volume":"5","author":"Sajjekhan","year":"2011","journal-title":"Med. Aromat. Plant Sci. Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"318","DOI":"10.31024\/ajpp.2018.4.3.13","article-title":"Phytochemical analysis and antimicrobial properties of leaves and Psidium guajava bark extracts","volume":"4","author":"Growther","year":"2018","journal-title":"Asian J. Pharm. Pharm."},{"key":"ref_13","first-page":"1720","article-title":"Antiprotozoal and antimicrobial activity of selected medicinal plants growing in Upper Egypt, Beni-Suef Region","volume":"4","author":"Gawad","year":"2015","journal-title":"World J. Pharm. Pharm. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.actatropica.2017.09.009","article-title":"Anti-trypanosoma, anti-leishmania and cytotoxic activities of natural products from Psidium brownianum Mart. ex DC. and Psidium guajava var. Pomifera analysed by LC\u2013MS","volume":"176","author":"Souza","year":"2017","journal-title":"Acta Trop."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11306-017-1227-6","article-title":"Dereplication of natural products from complex extracts by regression analysis and molecular networking: Case study of redox-active compounds from Viola alba subsp. dehnhardtii","volume":"13","author":"Chervin","year":"2017","journal-title":"Metabolomics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.fitote.2018.02.021","article-title":"A metabolomic approach to identify anti-hepatocarcinogenic compounds from plants used traditionally in the treatment of liver diseases","volume":"127","author":"Chassagne","year":"2018","journal-title":"Fitoterapia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.indcrop.2016.01.001","article-title":"Metabolomic tool to identify antioxidant compounds of Fraxinus angustifolia leaf and stem bark extracts","volume":"88","author":"Ayouni","year":"2016","journal-title":"Ind. Crops Prod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7946","DOI":"10.1021\/acs.analchem.6b00770","article-title":"Hydrogen rearrangement rules: Computational MS\/MS fragmentation and structure elucidation using ms-finder software","volume":"88","author":"Tsugawa","year":"2016","journal-title":"Anal. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.diabres.2006.01.010","article-title":"Effect of corosolic acid on postchallenge plasma glucose levels","volume":"73","author":"Fukushima","year":"2006","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/S0031-9422(00)86809-0","article-title":"Jacoumaric acid, a new triterpene ester from Jacaranda caucana","volume":"16","author":"Ogura","year":"1977","journal-title":"Phytochemistry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5936","DOI":"10.1021\/ol302849v","article-title":"Isolation and Biomimetic Synthesis of (\u00b1)-Guajadial B, a Novel Meroterpenoid from Psidium guajava","volume":"14","author":"Gao","year":"2012","journal-title":"Org. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Maestrini, M., Tava, A., Mancini, S., Salari, F., and Perrucci, S. (2019). In vitro anthelmintic activity of saponins derived from medicago spp. plants against donkey gastrointestinal nematodes. Vet. Sci., 6.","DOI":"10.3390\/vetsci6020035"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.intimp.2018.07.038","article-title":"Imidazolium salts as innovative agents against Leishmania amazonensis","volume":"63","author":"Martins","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.parint.2019.03.012","article-title":"White jute (Corchorus capsularis L.) leaf extract has potent leishmanicidal activity against Leishmania donovani","volume":"71","author":"Pramanik","year":"2019","journal-title":"Parasitol. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jep.2018.12.026","article-title":"In vitro antileishmanial activity of leaf and stem extracts of seven Brazilian plant species","volume":"232","author":"Paula","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_26","first-page":"50","article-title":"Antileishmanial potential of medicinal plant extracts from the North-West of Morocco","volume":"7","author":"Bouyahya","year":"2018","journal-title":"Beni-Suef Univ. J. Basic Appl. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bcab.2019.101117","article-title":"In vitro antileishmanial and antioxidant potential, cytotoxicity evaluation and phytochemical analysis of extracts from selected medicinally important plants","volume":"19","author":"Mehwish","year":"2019","journal-title":"Biocatal. Agric. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4993","DOI":"10.1021\/acs.jafc.7b01762","article-title":"Meroterpenoids with antitumor activities from Guava (Psidium guajava)","volume":"65","author":"Qin","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11030","DOI":"10.1021\/jf5049063","article-title":"Triterpenoid glycosides from Medicago sativa as antifungal agents against Pyricularia oryzae","volume":"62","author":"Abbruscato","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1078\/0944-7113-00381","article-title":"Antileishmanial activity of isolated triterpenoids from Pourouma guianensis","volume":"11","author":"Lopes","year":"2004","journal-title":"Phytomedicine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1590\/s1678-9946201961033","article-title":"Antileishmanial activity of Melampodium divaricatum and Casearia sylvestris essential oils on Leishmania amazonensis","volume":"61","author":"Moreira","year":"2019","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2933","DOI":"10.2147\/IDR.S211721","article-title":"Intracellular anti-leishmanial effect of Spergulin-A, a triterpenoid saponin of Glinus oppositifolius","volume":"12","author":"Banerjee","year":"2019","journal-title":"Infect. Drug Resistance"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7","DOI":"10.15562\/phytomedicine.2018.58","article-title":"A review on the phytochemistry and pharmacology of psidium guajava L. (Myrtaceae) and future direction","volume":"5","author":"Ngbolua","year":"2018","journal-title":"Discov. Phytomed."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1080\/14756366.2019.1616182","article-title":"Leishmania infantum arginase: biochemical characterization and inhibition by naturally occurring phenolic substances","volume":"34","author":"Garcia","year":"2019","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1016\/j.lfs.2006.08.007","article-title":"Corosolic acid prevents oxidative stress, inflammation and hypertension in SHR\/NDmcr-cp rats, a model of metabolic syndrome","volume":"79","author":"Yamaguchi","year":"2006","journal-title":"Life Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"277","DOI":"10.2754\/avb201887030277","article-title":"In vitro antibacterial activity of macelignan and corosolic acid against the bacterial bee pathogens Paenibacillus larvae and Melissococcus plutonius","volume":"87","author":"Kim","year":"2018","journal-title":"Acta Vet. Brno"},{"key":"ref_37","first-page":"4261","article-title":"Psidium guajava, a potential resource rich in corosolic acid revealed by high performance liquid chromatography","volume":"5","author":"Chen","year":"2011","journal-title":"J. Med. Plants Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1534735419861693","article-title":"The potential of chinese herbal medicines in the treatment of cervical cancer","volume":"18","author":"Hsiao","year":"2019","journal-title":"Integr. Cancer Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1248\/cpb.37.648","article-title":"Cytotoxic triterpenes from a chinese medicine, Goreishi","volume":"37","author":"Numata","year":"1989","journal-title":"Chem. Pharm. Bull."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1002\/ptr.2661","article-title":"Triterpene acids isolated from Lagerstroemia speciosa leaves as \u03b1-glucosidase inhibitors","volume":"23","author":"Hou","year":"2009","journal-title":"Phytother. Res."},{"key":"ref_41","first-page":"1190","article-title":"Selective activity of oleanolic and maslinic acids on the amastigote form of Leishmania spp.","volume":"16","author":"Sifaoui","year":"2017","journal-title":"Iran J. Pharm. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nmeth.3393","article-title":"MS-DIAL: data-independent MS\/MS deconvolution for comprehensive metabolome analysis","volume":"12","author":"Tsugawa","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Fonseca-Silva, F., Inacio, J.D.F., Canto-Cavalheiro, M.M., and Almeida-Amaral, E.E. (2011). Reactive oxygen species production and mitochondrial dysfunction contribute to quercetin induced death in Leishmania amazonensis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0014666"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/24\/4536\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:41:24Z","timestamp":1760190084000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/24\/4536"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,11]]},"references-count":43,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["molecules24244536"],"URL":"https:\/\/doi.org\/10.3390\/molecules24244536","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,11]]}}}