Cellular and molecular markers of therapeutic response of antihistamic drugs for the treatment of Visceral leishmaniasis

• Grant number: 19/10434-4
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2020
• End date: January 31, 2023
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Samanta Etel Treiger Borborema de Carvalho
• Grantee: Samanta Etel Treiger Borborema de Carvalho
• Host Institution: Instituto Adolfo Lutz (IAL). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: João Paulo dos Santos Fernandes

Abstract

Leishmaniases are a complex of infectious disease caused by Leishmania protozoan parasites transmitted by sand flies. The therapeutic regimen is restricted and due to the toxicity, variable efficacy, resistance, costs and inconvenient treatment schemes, there is an urgent need to identify and develop new alternatives. Drug repositioning consists in the search for new uses for approved drugs, is a therapeutic approach that has shown satisfactory results in this area. Analyzes of antihistaminic drugs reported their activity in vitro and in vivo against trypanosomatids. In our studies, we demonstrated the anti-Leishmania infantum activity of histamine H1 receptor antagonists, as cinnarizine, cyproheptadine and meclizine. In addition to potent activity and selectivity against intracellular amastigotes, the drugs induced important cellular alterations, damaging the bioenergetic system of the parasite. Thus, the present project aims to study the cellular mechanism of action and the gene expression profile of Leishmania infantum treated with antihistaminic drugs. For this, it will be evaluated different parameters to study the antiparasitic mechanism of action, such as (i) mitochondrial and plasma membrane potential; (ii) ATP level; (iii) reactive oxygen species level; (iv) intracellular calcium level; (v) intracellular thiol level. In parallel, it will be evaluated the cellular ultrastructures of the parasite and the variability in the expression of specific genes. The search for possible cellular and molecular mechanism of action of antihistaminic drugs could contribute to the selection of new therapeutic targets, aiming to identify therapeutic alternatives of drugs already approved to treat visceral leishmaniasis. (AU)

Scientific publications

(4)

(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)

TEMPONE, ANDRE G.; PIEPER, PAULINE; BORBOREMA, SAMANTA E. T.; THEVENARD, FERNANDA; LAGO, JOAO HENRIQUE G.; CROFT, SIMON L.; ANDERSON, EDWARD A.. Marine alkaloids as bioactive agents against protozoal neglected tropical diseases and malaria. NATURAL PRODUCT REPORTS, v. 38, n. 12, p. 2214-2235, DEC 15 2021. (18/10279-6, 19/10434-4, 18/07885-1)

TEMPONE, ANDRE G.; PIEPER, PAULINE; BORBOREMA, SAMANTA E. T.; THEVENARD, FERNANDA; LAGO, JOAO HENRIQUE G.; CROFT, SIMON L.; ANDERSON, EDWARD A.. Marine alkaloids as bioactive agents against protozoal neglected tropical diseases and malaria. NATURAL PRODUCT REPORTS, APR 2021. (19/10434-4, 18/10279-6, 18/07885-1)

LIMA, MARTA LOPES; AMARAL, MAIARA; TREIGER BORBOREMA, SAMANTA ETEL; TEMPONE, ANDRE GUSTAVO. Evaluation of antileishmanial potential of the antidepressant escitalopram in Leishmania infantum. Journal of Pharmaceutical and Biomedical Analysis, v. 209, FEB 5 2022. (19/10434-4, 17/50333-7)

LIMA, MARTA LOPES; ABENGOZAR, MARIA A.; TORRES-SANTOS, EDUARDO CAIO; BORBOREMA, SAMANTA ETEL TREIGER; GODZIEN, JOANNA; LOPEZ-GONZALVEZD, ANGELES; BARBAS, CORAL; RIVAS, LUIS; TEMPONE, ANDRE GUSTAVO. Energy metabolism as a target for cyclobenzaprine: A drug candidate against Visceral Leishmaniasis. BIOORGANIC CHEMISTRY, v. 127, p. 11-pg., 2022-07-13. (17/50333-7, 19/10434-4, 21/04464-8)