Banca de DEFESA: LEANDRO DO NASCIMENTO MARTINEZ

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
DISCENTE : LEANDRO DO NASCIMENTO MARTINEZ
DATA : 16/03/2020
HORA: 14:30
LOCAL: Programa de Pós Graduação em Biologia
TÍTULO:

In vitro evaluation of synthetic compounds derived from Bi-triazoles against sexual and asexual forms of P. falciparum

PALAVRAS-CHAVES:

Key words: bis-triazoles, antimalarial, Plasmodium falciparum.

 

PÁGINAS: 90
GRANDE ÁREA: Ciências Biológicas
ÁREA: Bioquímica
RESUMO:

ABSTRACT

 

Considered one of the oldest diseases of mankind, the malaria remains a serious public health problem. Currently, five species of Plasmodium are described to cause malaria in humans and the transmission occurs mainly during the blood repast of infected female of the genus Anopheles spp. Severe malaria caused by Plasmodium falciparum is characterized by the severe clinical features that affects organs and vital systems of the organism. In addition, there are reports of resistance of P. falciparum to some reference drugs. Faced with this and other aggravating factors, the malaria continues to cause the death of more than 400,000 people annually and more than 200 million new cases are reported worldwide. Thus, the development of new drugs for the treatment of that disease is becoming increasingly necessary. In this context, bi-triazoles (targets of this study) are classes of substances that have diverse biological activities and have shown to be promising in the development of new prototypes to combat malaria. The objective of the present study is to evaluate the in vitro antimalarial activity of four compounds from bi-triazole family against P. falciparum. For the bioassays the strain W2 (CQ-Chloroquine resistant) and NF54 (CQ-Chloroquine sensitive) were used. For the IC50 evaluation the Sybr Green I method was used. The cytotoxicity assay assessed by means of the colorimetric assay MTT (3 - ([(4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium]) using the HepG2 cell line, then the selectivity index (IS) of each test compound was calculated. In parallel, the hemolysis test was performed and the blocking activity of the exflagelation of the compounds was also verified. Based on the results obtained for the four compounds, it was possible to observe the potency of compound 10RJ (1-(5-(Trifluoromethyl) -4H-1,2,4-triazol-3-yl)-1H-1,2,3-triazol-4-yl) methyl acetate, with inhibition of the parasite in 0.45 μM IC 50. The compounds showed no cytotoxic activity against HepG2 (CC50 ˃ 500 μM), nor exacerbated haemolytic rates. The selectivity index for compound 10RJ was 1.111. For the sexual forms, the inhibition of exflagelation was 79.2%. The data will be complemented with compound combination analysis. The results of this study may contribute to increase the database on the profile and action of bi-triazole derivatives with the antimalarial action, and to choose new promising alternatives for the treatment of this disease.

MEMBROS DA BANCA:
Interno - 004.161.386-40 - ANDREIMAR MARTINS SOARES - FIOCRUZ
Interno - 218.429.088-20 - CAROLINA BIONI GARCIA TELES - FIOCRUZ
Interno - 1786399 - DHELIO BATISTA PEREIRA