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Use of drug repurposing and natural product bioprospection to characterize compounds with in vitro and in vivo leishmanicidal action

Grant number:16/00468-0
Support Opportunities:Regular Research Grants
Start date: December 01, 2016
End date: November 30, 2018
Field of knowledge:Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
Principal Investigator:Luiz Felipe Domingues Passero
Grantee:Luiz Felipe Domingues Passero
Host Institution: Instituto de Biociências (IB-CLP). Universidade Estadual Paulista (UNESP). Campus Experimental do Litoral Paulista. São Vicente , SP, Brazil
City of the host institution:São Vicente
Associated researchers:João Henrique Ghilardi Lago

Abstract

Leishmaniasis are diseases caused by parasitic protozoal of Leishmania genus. There are different species able to infect humans and they induce distinct clinical forms, and surprisingly the therapy is based on two drugs that induce serious side effects in patients. Therefore, it is necessary and urgent searching for new candidates to the therapy. Thus, the aim of this project is to characterize the leishmanicidal action (in vitro and in vivo) of pure and synthetic compounds. The drugs Butenafine, Naftifine, Fenticonazole and Rosuvastatin will be commercially purchased. Pure natural products will be purified through bioprospection procedures from crude extract produced with the leaves of the following vegetal species: Euphorbia tirucalli, Gochnatia polymorpha, Alchornea glandulosa, Ruta graveolens and Solanum americanum. Pure compounds presenting low cytotoxic activity and antileishmanial activity similar or higher than Amphotericin B and/or miltefosine, will be evaluated concerning their action mechanisms, and will be selected for in vivo studies, that will be conducted in animal models of tegumentar and visceral leishmaniasis. In these animals, parasitological, pathological and immunological studies will be conducted. In previous studies, we demonstrated the efficacy of ursolic acid in visceral and tegumentar leishmaniasis, and for this reason, this compound will be loaded in nanocarriers in the attempt to increase its therapeutic effect in animal models. Finally, the main purpose of this project is to characterize new synthetic and natural prototypes with leishmanicidal action in vitro and in vivo, aiming at increasing the current therapeutic arsenal of leishmaniasis. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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VEICULO: TITULO (DATA)
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Scientific publications (16)
(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)
MARIA L. A. C. BORDON; MÁRCIA D. LAURENTI; SUSAN PEREIRA RIBEIRO; MARCOS H. TOYAMA; DANIELA DE O. TOYAMA; LUIZ FELIPE D. PASSERO. Effect of phospholipase A2 inhibitors during infection caused by Leishmania (Leishmania) amazonensis. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 24, . (16/00468-0)
JESUS, JESSICA ADRIANA; FRAGOSO DA SILVA, THAYS NICOLLI; YAMAMOTO, EDUARDO SEIJI; G. LAGO, JOAO HENRIQUE; DALASTRA LAURENTI, MARCIA; PASSERO, LUIZ FELIPE DOMINGUES. Ursolic Acid Potentializes Conventional Therapy in Experimental Leishmaniasis. PATHOGENS, v. 9, n. 10, . (18/24077-6, 18/07885-1, 16/00468-0, 16/10324-6)
JESUS, JESSICA ADRIANA; SOUSA, ILZA MARIA OLIVEIRA; DA SILVA, THAYS NICOLLI FRAGOSO; FERREIRA, AUREA FAVERO; LAURENTI, MARCIA DALASTRA; ANTONANGELO, LEILA; FARIA, CAROLINE SILVERIO; DA COSTA, PAULO CARDOSO; DE CARVALHO FERREIRA, DOMINGOS; PASSERO, LUIZ FELIPE DOMINGUES. Preclinical Assessment of Ursolic Acid Loaded into Nanostructured Lipid Carriers in Experimental Visceral Leishmaniasis. PHARMACEUTICS, v. 13, n. 6, . (18/04080-2, 16/10324-6, 18/24077-6, 16/00468-0)
LALATSA, AIKATERINI; STATTS, LARRY; DE JESUS, JESSICA ADRIANA; ADEWUSI, OLIVIA; AUXILIADORA DEA-AYUELA, MARIA; BOLAS-FERNANDEZ, FRANCISCO; LAURENTI, MARCIA DALASTRA; DOMINGUES PASSERO, LUIZ FELIPE; SERRANO, DOLORES R.. Topical buparvaquone nano-enabled hydrogels for cutaneous leishmaniasis. International Journal of Pharmaceutics, v. 588, . (16/00468-0)
CALDAS, LHAIS ARAUJO; YOSHINAGA, MEIRE L.; FERREIRA, MARCELO J. P.; LAGO, JOAO H. G.; DE SOUZA, ADRIANA B.; LAURENTI, MARCIA D.; PASSERO, LUIZ FELIPE D.; SARTORELLI, PATRICIA. Antileishmanial activity and ultrastructural changes of sesquiterpene lactones isolated from Calea pinnatifida (Asteraceae). BIOORGANIC CHEMISTRY, v. 83, p. 348-353, . (16/24985-4, 16/00468-0)
BRITO, JULIANA R.; PASSERO, LUIZ FELIPE D.; BEZERRA-SOUZA, ADRIANA; LAURENTI, MARCIA D.; ROMOFF, PAULETE; BARBOSA, HENRIQUE; FERREIRA, EDGARD A.; LAGO, JOAO HENRIQUE G.. Antileishmanial activity and ultrastructural changes of related tetrahydrofuran dineolignans isolated from Saururus cernuus L. (Saururaceae). Journal of Pharmacy and Pharmacology, v. 71, n. 12, p. 1871-1878, . (18/07885-1, 16/00468-0)
OLIVEIRA, EMERSON A.; MARTINS, EUDER G. A.; SOARES, MARISI G.; CHAGAS-PAULA, DANIELA A.; PASSERO, LUIZ F. D.; SARTORELLI, PATRICIA; BALDIM, JOAO L.; LAGO, JOAO HENRIQUE G.. A Comparative Study on Chemical Composition, Antileishmanial and Cytotoxic Activities of the Essential Oils from Leaves of Guarea macrophylla (Meliaceae) from Two Different Regions of São Paulo State, Brazil, Using Multivariate Statistical Analysis. Journal of the Brazilian Chemical Society, v. 30, n. 7, p. 1395-1405, . (16/00468-0, 18/07885-1, 16/19269-8)
BEZERRA-SOUZA, ADRIANA; JESUS, JESSICA A.; LAURENTI, MARCIA D.; LALATSA, AIKATERINI; SERRANO, DOLORES R.; PASSERO, LUIZ FELIPE D.. Nanoemulsified Butenafine for Enhanced Performance against Experimental Cutaneous Leishmaniasis. JOURNAL OF IMMUNOLOGY RESEARCH, v. 2021, . (16/00468-0, 18/24077-6, 17/09405-4)
BEZERRA-SOUZA, ADRIANA; FERNANDEZ-GARCIA, RAQUEL; RODRIGUES, GABRIELA F.; BOLAS-FERNANDEZ, FRANCISCO; LAURENTI, MARCIA DALASTRA; PASSERO, LUIZ FELIPE; LALATSA, AIKATERINI; SERRANO, DOLORES R.. Repurposing Butenafine as An Oral Nanomedicine for Visceral Leishmaniasis. PHARMACEUTICS, v. 11, n. 7, . (17/09405-4, 16/00468-0)
JESUS, JESSICA A.; FRAGOSO, THAIS N.; YAMAMOTO, EDUARDO S.; LAURENTI, MARCIA D.; SILVA, MARCELO S.; FERREIRA, AUREA F.; LAGO, JOAO HENRIQUE G.; GOMES, GABRIELA S.; PASSERO, LUIZ FELIPE D.. Therapeutic effect of ursolic acid in experimental visceral leishmaniasis. INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE, v. 7, n. 1, p. 1-11, . (13/10133-8, 16/00468-0, 13/16297-2, 15/11936-2)
ADRIANA JESUS, JESSICA; LAURENTI, MARCIA DALASTRA; LOPES SILVA, MATHEUS; GHILARDI LAGO, JOAO HENRIQUE; DOMINGUES PASSERO, LUIZ FELIPE. Leishmanicidal Activity and Ultrastructural Changes of Maslinic Acid Isolated from Hyptidendron canum. Evidence-based Complementary and Alternative Medicine, v. 2021, . (16/10324-6, 16/00468-0, 21/02789-7, 18/04080-2)
YAMAMOTO, EDUARDO SEIJI; DE JESUS, JESSICA ADRIANA; BEZERRA-SOUZA, ADRIANA; BRITO, JULIANA R.; LAGO, JOAO HENRIQUE G.; LAURENTI, MARCIA DALASTRA; PASSERO, LUIZ FELIPE DOMINGUES. Tolnaftate inhibits ergosterol production and impacts cell viability of Leishmania sp.. BIOORGANIC CHEMISTRY, v. 102, . (15/17623-6, 18/07885-1, 16/00468-0)
DE JESUS, JESSICA ADRIANA; LAURENTI, MARCIA DALASTRA; ANTONANGELO, LEILA; FARIA, CAROLINE SILVERIO; LAGO, JOAO HENRIQUE GHILARDI; PASSERO, LUIZ FELIPE DOMINGUES. Related Pentacyclic Triterpenes Have Immunomodulatory Activity in Chronic Experimental Visceral Leishmaniasis. JOURNAL OF IMMUNOLOGY RESEARCH, v. 2021, . (16/00468-0, 18/07885-1, 16/10324-6)
YAMAMOTO, EDUARDO SEIJI; JESUS, JESSICA ADRIANA; BEZERRA-SOUZA, ADRIANA; LAURENTI, MARCIA DALASTRA; RIBEIRO, SUSAN PEREIRA; DOMINGUES PASSERO, LUIZ FELIPE. Activity of Fenticonazole, Tioconazole and Nystatin on New World Leishmania Species. CURRENT TOPICS IN MEDICINAL CHEMISTRY, v. 18, n. 27, p. 2338-2346, . (15/17623-6, 16/00468-0)
BORDON, MARIA L. A. C.; LAURENTI, MARCIA D.; RIBEIRO, SUSAN PEREIRA; TOYAMA, MARCOS H.; TOYAMA, DANIELA DE O.; PASSERO, LUIZ FELIPE D.. Effect of phospholipase A(2) inhibitors during infection caused by Leishmania (Leishmania) amazonensis. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 24, . (16/00468-0)
DE LIMA, SARAH KYMBERLY SANTOS; CAVALLONE, ITALO NOVAIS; OLIVEIRA, KARINE SOARES; PASSERO, LUIZ FELIPE DOMINGUES; LAURENTI, MARCIA DALASTRA; JESUS, JESSICA ADRIANA; MARINSEK, GABRIELA PUSTIGLIONE; CHUCRI, THAIS MARTINS; MARI, RENATA DE BRITTO. Infection with Leishmania (Leishmania) infantum Changes the Morphology and Myenteric Neurons of the Jejunum of Golden Hamsters. PARASITOLOGIA, v. 1, n. 4, p. 13-pg., . (14/07793-9, 18/04869-5, 19/21557-0, 18/24077-6, 16/00468-0, 18/06778-7)