{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T10:17:00Z","timestamp":1789208220044,"version":"build-2803163510"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100003593","name":"MCTI | Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["research fellows"],"award-info":[{"award-number":["research fellows"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["26\/110.731\/2012"],"award-info":[{"award-number":["26\/110.731\/2012"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["26\/110.613\/2012"],"award-info":[{"award-number":["26\/110.613\/2012"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["26\/110.401\/2014"],"award-info":[{"award-number":["26\/110.401\/2014"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is the second major cause of death by parasites, after malaria. The arsenal of drugs against leishmaniasis is small, and each has a disadvantage in terms of toxicity, efficacy, price, or treatment regimen. Our group has focused on studying new drug candidates as alternatives to current treatments. The pterocarpanquinone LQB-118 was designed and synthesized based on molecular hybridization, and it exhibited antiprotozoal and anti-leukemic cell line activities. Our previous work demonstrated that LQB-118 was an effective treatment for experimental cutaneous leishmaniasis. In this study, we observed that treatment with 10 mg\/kg of body weight\/day LQB-118 orally inhibited the development of hepatosplenomegaly with a 99% reduction in parasite load. An\n            <jats:italic>in vivo<\/jats:italic>\n            toxicological analysis showed no change in the clinical, biochemical, or hematological parameters. Histologically, all of the analyzed organs were normal, with the exception of the liver, where focal points of necrosis with leukocytic infiltration were observed at treatment doses 5 times higher than the therapeutic dose; however, these changes were not accompanied by an increase in transaminases. Our findings indicate that LQB-118 is effective at treating different clinical forms of leishmaniasis and presents no relevant signs of toxicity at therapeutic doses; thus, this framework is demonstrated suitable for developing promising drug candidates for the oral treatment of leishmaniasis.\n          <\/jats:p>","DOI":"10.1128\/aac.01787-15","type":"journal-article","created":{"date-parts":[[2016,4,12]],"date-time":"2016-04-12T03:39:01Z","timestamp":1460432341000},"page":"3794-3801","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Preclinical Studies Evaluating Subacute Toxicity and Therapeutic Efficacy of LQB-118 in Experimental Visceral Leishmaniasis"],"prefix":"10.1128","volume":"60","author":[{"given":"Ed\u00e9zio Ferreira","family":"Cunha-J\u00fanior","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica de Tripanosomat\u00eddeos, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago Martino","family":"Martins","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunologia Aplicada e Bioquimica de Prote\u00ednas e Produtos Naturais, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilene Marcuzzo","family":"Canto-Cavalheiro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica de Tripanosomat\u00eddeos, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Roberto","family":"Marques","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunologia Aplicada e Bioquimica de Prote\u00ednas e Produtos Naturais, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyzabeth Avvad","family":"Portari","sequence":"additional","affiliation":[{"name":"Departamento de Patologia e Laborat\u00f3rios, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marsen Garcia Pinto","family":"Coelho","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunologia Aplicada e Bioquimica de Prote\u00ednas e Produtos Naturais, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaquip Daher","family":"Netto","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Qu\u00edmica, Universidade Federal do Rio de Janeiro, Maca\u00e9, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Roberto Ribeiro","family":"Costa","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia Costa de Carvalho","family":"Sabino","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunologia Aplicada e Bioquimica de Prote\u00ednas e Produtos Naturais, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo Caio","family":"Torres-Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Bioqu\u00edmica de Tripanosomat\u00eddeos, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035671"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03635.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2006.09.004"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2013.08.005"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0103-50532009000100026"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2009.12.073"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2011.09.025"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-010-9453-z"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2011.11.008"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2014.2615"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr158"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0109672"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks498"},{"key":"e_1_3_3_15_2","volume-title":"OECD guidelines for the testing of chemicals, section 4","author":"Organisation for Economic Co-operation and Development","year":"2008","unstructured":"Organisation for Economic Co-operation and Development. 2008. Test no. 407: repeated dose 28-day oral toxicity study in rodents. OECD guidelines for the testing of chemicals, section 4. OECD Publishing, Paris, France."},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/283157a0"},{"key":"e_1_3_3_17_2","volume-title":"Principles and methods of toxicology","author":"Hayes AW","year":"1994","unstructured":"Hayes AW. 1994. Principles and methods of toxicology, 3rd ed, p 579\u2013647. Raven Press Ltd., New York, NY.","edition":"3"},{"key":"e_1_3_3_18_2","volume-title":"IDEXX VETTest chemistry analyzer","author":"Dwyer LA","year":"2000","unstructured":"Dwyer LA. 2000. IDEXX VETTest chemistry analyzer. IDEXX Laboratories, Inc., Fairfax, VA."},{"key":"e_1_3_3_19_2","volume-title":"Wintrobe's clinical hematology","author":"Greer JP","year":"2003","unstructured":"Greer JP, Foerster J, Lukens JN (ed). 2003. Wintrobe's clinical hematology, 11th ed, p 16\u201335. Lippincott Williams & Wilkins, Philadelphia, PA.","edition":"11"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2423(08)60414-X"},{"key":"e_1_3_3_21_2","volume-title":"Manual of histological techniques and their diagnostics application","author":"Bancroft JD","year":"1994","unstructured":"Bancroft JD, Cook HC. 1994. Manual of histological techniques and their diagnostics application. Churchill Livingstone, London, United Kingdom."},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2003.09.010"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr409"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.8.1630"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.1998.tb01170.x"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.9.2167"},{"key":"e_1_3_3_27_2","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/9781118517000.ch12","volume-title":"Nonclinical safety assessment: a guide to international pharmaceutical regulations","author":"Azri-Meehan S","year":"2013","unstructured":"Azri-Meehan S, Latriano L. 2013. Repeated-dose toxicity studies in nonclinical drug development, p 197\u2013218. In Brock WJ, Hastings KL, McGown KM (ed), Nonclinical safety assessment: a guide to international pharmaceutical regulations. John Wiley & Sons, Chichester, United Kingdom."},{"key":"e_1_3_3_28_2","volume-title":"Guidance for industry: content and format of investigational new drug applications (INDs) for phase 1 studies of drugs, including well-characterized, therapeutic, biotechnology-derived products","author":"FDA Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research","year":"1995","unstructured":"FDA Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research. 1995. Guidance for industry: content and format of investigational new drug applications (INDs) for phase 1 studies of drugs, including well-characterized, therapeutic, biotechnology-derived products. FDA, Rockville, MD."},{"key":"e_1_3_3_29_2","first-page":"36","article-title":"Comunica\u00e7\u00e3o \u00e0 Sess\u00e3o de 24 de abril de 1912 da Sociedade Brasileira de Dermatologia","volume":"1","author":"Vianna G","year":"1912","unstructured":"Vianna G. 1912. Comunica\u00e7\u00e3o \u00e0 Sess\u00e3o de 24 de abril de 1912 da Sociedade Brasileira de Dermatologia. Arch Bras Med 1:36\u201338.","journal-title":"Arch Bras Med"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(95)90572-3"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1804.110841"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks275"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis424"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1086\/503371"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(00)00129-0"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/ci300367a"},{"key":"e_1_3_3_37_2","doi-asserted-by":"crossref","first-page":"S107","DOI":"10.1093\/infdis\/jiv009","article-title":"Drug metabolism and drug interactions: potential application to antituberculosis drugs","volume":"211","author":"Sahasrabudhe V","year":"2015","unstructured":"Sahasrabudhe V, Zhu T, Alfin V, Tse S. 2015. Drug metabolism and drug interactions: potential application to antituberculosis drugs. J Infect Dis 211(Suppl 3):S107\u2013S114.","journal-title":"J Infect Dis"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.3923\/pjbs.2008.1630.1633"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.4103\/0971-6580.103656"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.2012.01567.x"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1186\/1297-9716-42-39"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.12.4978-4983.1997"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1177\/096032719201100409"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.3.654"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1086\/315268"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01787-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01787-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:49:11Z","timestamp":1645476551000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01787-15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6]]},"references-count":44,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["10.1128\/AAC.01787-15"],"URL":"https:\/\/doi.org\/10.1128\/aac.01787-15","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6]]},"assertion":[{"value":"2015-07-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-04-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-05-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}