{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T23:46:38Z","timestamp":1772754398871,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Global Health and Tropical Medicine","award":["IHMT-UID\/multi\/04413\/2013"],"award-info":[{"award-number":["IHMT-UID\/multi\/04413\/2013"]}]},{"name":"Global Health and Tropical Medicine","award":["PTDC\/CVT-CVT\/28908\/2017"],"award-info":[{"award-number":["PTDC\/CVT-CVT\/28908\/2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Leishmanolysin, also known as major promastigote protease (PSP) or gp63, is the most abundant surface glycoprotein of Leishmania spp., and has been extensively studied and recognized as the main parasite virulence factor. Characterized as a metalloprotease, gp63 can be powerfully inactivated in the presence of a metal chelator. In this study, we first used the structural parameters of a 7-hydroxycoumarin derivative, L1 compound, to evaluate the theoretical\u2013computational experiments against gp63, comparing it with an available metal chelator already described. The methodology followed was (i) analysis of the three-dimensional structure of gp63 as well as its active site, and searching the literature and molecular databases for possible inhibitors; (ii) molecular docking simulations and investigation of the interactions in the generated protein\u2013ligand complexes; and (iii) the individual energy of the gp63 amino acids that interacted most with the ligands of interest was quantified by ab initio calculations using Molecular Fraction with Conjugated Caps (MFCC). MFCC still allowed the final quantum balance calculations of the protein interaction to be obtained with each inhibitor candidate binder. L1 obtained the best energy quantum balance result with \u22122 eV, followed by DETC (\u22121.4 eV), doxycycline (\u22121.3 eV), and 4-terpineol (\u22120.6 eV), and showed evidence of covalent binding in the enzyme active site. In vitro experiments confirmed L1 as highly effective against L. amazonensis parasites. The compound also exhibited a low cytotoxicity profile against mammalian RAW and 3T3 cells lines, presenting a selective index of 149.19 and 380.64 \u00b5M, respectively. L1 induced promastigote forms\u2019 death by necrosis and the ultrastructural analysis revealed disruption in membrane integrity. Furthermore, leakage of the contents and destruction of the parasite were confirmed by Spectroscopy Dispersion analysis. These results together suggested L1 has a potential effect against L. amazonensis, the etiologic agent of diffuse leishmaniasis, and the only one that currently does not have a satisfactory treatment.<\/jats:p>","DOI":"10.3390\/ijms23158553","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T23:49:27Z","timestamp":1659397767000},"page":"8553","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Quantum Biochemistry Screening and In Vitro Evaluation of Leishmania Metalloproteinase Inhibitors"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6948-9823","authenticated-orcid":false,"given":"Cl\u00e1udia Jassica Gon\u00e7alves","family":"Moreno","sequence":"first","affiliation":[{"name":"Laboratory of Immunoparasitology, Department of Clinical and Toxicological Analysis, Health Sciences Center, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"},{"name":"Postgraduate Program in Pharmaceutical Sciences, Health Sciences Center, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"},{"name":"Postgraduate Program in Biochemistry, Biosciences Center, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"}]},{"given":"Henriqueta Monalisa","family":"Farias","sequence":"additional","affiliation":[{"name":"Academic Unit of Physics, Mathematics of the Education and Health Center, Federal University of Campina Grande, Campina Grande 58428-830, Brazil"}]},{"given":"Rafael","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Academic Unit of Physics, Mathematics of the Education and Health Center, Federal University of Campina Grande, Campina Grande 58428-830, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3113-7187","authenticated-orcid":false,"given":"Talita","family":"Brito","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Health Sciences, Health Sciences Center, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3100-0420","authenticated-orcid":false,"given":"Johny","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoparasitology, Department of Clinical and Toxicological Analysis, Health Sciences Center, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"},{"name":"Postgraduate Program in Biochemistry, Biosciences Center, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9300-8623","authenticated-orcid":false,"suffix":"Jr.","given":"Francimar Lopes","family":"de Sousa","sequence":"additional","affiliation":[{"name":"Laboratory of Chemistry of Coordination and Polymers (LQCPol), Institute of Chemistry Chemistry Institute, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8419-4292","authenticated-orcid":false,"given":"Mayara Jane Campos de","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Laboratory of Chemistry of Coordination and Polymers (LQCPol), Institute of Chemistry Chemistry Institute, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0417-8677","authenticated-orcid":false,"given":"Bruno","family":"Amorim","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, Health Sciences Center, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9264-3887","authenticated-orcid":false,"given":"Gabriela","family":"Santos-Gomes","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, Institute of Hygiene and Tropical Medicine, IHMT, NOVA University of Lisbon\u2014UNL, 1349-008 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7770-0492","authenticated-orcid":false,"given":"Daniel","family":"Pontes","sequence":"additional","affiliation":[{"name":"Laboratory of Chemistry of Coordination and Polymers (LQCPol), Institute of Chemistry Chemistry Institute, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2252-1221","authenticated-orcid":false,"given":"Hugo Alexandre Oliveira","family":"Rocha","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Biochemistry, Biosciences Center, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"},{"name":"Postgraduate Program in Health Sciences, Health Sciences Center, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"}]},{"given":"Nilton Fereira","family":"Frazao","sequence":"additional","affiliation":[{"name":"Academic Unit of Physics, Mathematics of the Education and Health Center, Federal University of Campina Grande, Campina Grande 58428-830, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1000-0149","authenticated-orcid":false,"given":"Marcelo Sousa","family":"Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoparasitology, Department of Clinical and Toxicological Analysis, Health Sciences Center, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"},{"name":"Postgraduate Program in Pharmaceutical Sciences, Health Sciences Center, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"},{"name":"Postgraduate Program in Biochemistry, Biosciences Center, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil"},{"name":"Global Health and Tropical Medicine, GHTM, Institute of Hygiene and Tropical Medicine, IHMT, NOVA University of Lisbon\u2014UNL, 1349-008 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,2]]},"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":"Akhoundi, M., Kuhls, K., Cannet, A., Votypka, J., Marty, P., Delaunay, P., and Sereno, D. 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