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 type: Regular Research Grants
• Duration: December 01, 2016 - November 30, 2018
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Luiz Felipe Domingues Passero
• Grantee: Luiz Felipe Domingues Passero
• Home Institution: Instituto de Biociências (IB-CLP). Universidade Estadual Paulista (UNESP). Campus Experimental do Litoral Paulista. São Vicente , SP, Brazil
• Assoc. 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)

Scientific publications

(8)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

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, DEC 2019. Web of Science Citations: 0.

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 JUL 2019. Web of Science Citations: 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 Sao Paulo State, Brazil, Using Multivariate Statistical Analysis. Journal of the Brazilian Chemical Society, v. 30, n. 7, p. 1395-1405, JUL 2019. Web of Science Citations: 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, MAR 2019. Web of Science Citations: 1.

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, AUG 27 2018. Web of Science Citations: 2.

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, p. -, 2018.

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, 2018. Web of Science Citations: 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, APR 2017. Web of Science Citations: 15.