Banca de QUALIFICAÇÃO: JONATHAS ALVES DE MELO

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : JONATHAS ALVES DE MELO
DATE: 23/11/2020
TIME: 14:30
LOCAL: Videoconferência
TITLE:

CHARACTERIZATION OF ANTI-PARASITIC ACTIVITY OF SYNTHETIC COMPOUNDS BASED ON BISPHOSPHONATES

KEY WORDS:

Bisphosphonate; Chagas disease; Trypanossoma cruzi.

PAGES: 60
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Chagas disease is currently a major public health problem for about 7 million people in the infected world, it is endemic in 21 Countries in Latin America. In addition approximately 70 million people are at risk of contracting the disease, and each year causes 14,000 deaths worldwide. It has two characteristic stages, acute and chronic, and the main treatment consists in the use of two drugs, Benznidazole (BNZ) and Nifurtimox (NFX). The aforementioned drugs have great benefit in the acute phase, obtaining resolution in up to 80% of the patients treated, however, in the chronic phase, the success after treatment varies from 7 to 10% for NFX and between 2 to 40% for BNZ, in addition to this low efficacy, there are adverse effects that are an important factor to lead patients to treatment abandonment , as well as the genetic diversity of the parasite that provides resistance to the drug. In recent years, several strategies have been reported aiming at the development of new drugs with antiparasitic activity, especially in the context of infections caused by trypanososides, such as Leishmania spp. and T. cruzi. Given the need to develop new therapeutic outflows, bisphosphonate-based compounds have been gaining prominence in the control of these Neglected Tropical Diseases because they have already reported antiparasitic activity. Some of these compounds are already approved to be used in the treatment of various diseases in humans. The antiparasitic activity of these compounds is related to the inhibition capacity of important enzymes involved in the biosynthesis of sterol. Its mechanism of action occur in the inhibition of Farnesil Pyrophosphate Synthesis, which is an important enzyme of the production pathway of isoprenoid compounds that perform vital functions in cells, among these products are cholesterol and sterol, responsible for the formation of the cell membrane and organelles. These intermediate compounds are indispensable for cells, especially for trypanososides, as they are important roles in the production of components that act in cell differentiation and growth, as well as antioxidant effect. Knowing the properties of bisphosphonates, organic compounds were developed based on bisphosphonates and the objective was to present the trypanocidal activity of these as potential new antiparasitic drugs, more specifically with emphasis on the therapeutic control of Chagas disease. The 25 synthesized compounds were incubated with trypanososides in 2 stages, in the first stage they were treated for 24 and 48 hours with bisphosphonates, after this incubation time seven of the compounds used demonstrated good results, which ranged between 42 and approximately 90%. These data were taken as selection criteria for performing in silico tests. These compounds were tested in a Y/WS strain that belongs to DTU II that has a peridomiciliary cycle and which proves to be one of the most resistant.

BANKING MEMBERS:
Externa à Instituição - CLÁUDIA JASSICA GONÇALVES MORENO
Interno - 1880243 - DANIEL CARLOS FERREIRA LANZA
Presidente - 2195251 - HUGO ALEXANDRE DE OLIVEIRA ROCHA