Síntese, caracterização e avaliação da atividade biológica de nitrichalconas e de chalconas derivadas da 6-acetil-2h-1,4-benzoxazin-3(4H)-ona

Abstract

Este trabalho teve como objetivo a síntese e caracterização de duas séries de chalconas, uma derivada da CH8 (previamente patenteada pelo grupo), contendo o grupo nitro na posição 3 ou 3' (série ML) e a outra derivada da 6-acetil-2H-1,4-benzoxazin-3(4H)-ona (série MN), bem como a posterior avaliação biológica de todos os compostos obtidos. Os compostos da série ML foram avaliados como inibidores das proteínas tirosina fosfatase PtpA e PtpB de Mycobacterium tuberculosis, e não apresentaram atividades significativas. Foram também avaliados como agentes anti-leishmania, e de modo geral observou-se que apresentaram inibição superior a 60% para as formas amastigotas de Leishmania amazonensis, sendo (2E)-1-(4-metoxifenil)-3-(2-nitrofenil)prop-2-en-1-ona (ML3) o mais promissor, devido ao seu elevado índice de seletividade quando comparado aos outros compostos do estudo (IS = 15,58). A avaliação dos compostos da série MN revelou 3 chalconas com promissora atividade inibitória das proteínas PtpA e PtpB de Mycobacterium tuberculosis, para os quais foram determinados os valores de IC50: (2E)-6-(3-(3,4-diclorofenil)acriloil)-2H-benzo[b][1,4]oxazin-3(4H)-ona (MN1) (IC50 = 18,44 ± 4,71 para PtpB e IC50 = 28,11 ± 0,33 para PtpA), (2E)-6-(3-(4-bromofenil)acriloil)-2H-benzo[b][1,4]oxazin-3(4H)-ona (MN5) (IC50 = 16,71 ± 0,29 para PtpA) e (2E)-6-(3-(3nitrofenil)acriloil)-2H-benzo[b][1,4]oxazin-3(4H)-ona (MN10) ( IC50=12,04 ± 1,90 para PtpB). O composto com melhor atividade frente a PtpB foi MN10 e frente a PtpA foi MN5.<br>

Abstract : This work aimed to objective the synthesis and characterization of two series of chalcones, a derivative of CH8 (previously patented by the group ), containing the nitro group in position 3 or 3' (ML series) and the other derived from 6-acetyl-2H-1,4-benzoxazin-3(4H )-one (MN series), as well as subsequent biological evaluation of all the compounds obtained. The compounds of ML series were evaluated as inhibitors of proteins tyrosine phosphatase PtpA and PtpB of Mycobacterium tuberculosis, and no present significant activities. Also were evaluated as anti-leishmania agents and in general was observed that they presented 60% inhibition superior to amastigote forms of L. amazonensis, being (2E)-1-(4-methoxyphenyl)-3-(2-nitrophenyl)prop-2-en-1-one (ML3) most promising due to their high selectivity index as compared to the other compounds of the study (IS=15.58). The evaluation of the compounds of MN series showed 3 chalcones with promising inhibitory activity of the proteins PtpA and PtpB of Mycobacterium tuberculosis, for which were determined IC50 values: (2E)-6-(3-(3,4-dichlorophenyl)acryloyl)-2H- benzo [b][1,4]oxazin- 3(4H) -one (MN1) (IC50= 18.44 ± 4.71 for PtpB and IC50= 28.11 ± 0.33 for PtpA), (2E)-6-(3-(4-bromophenyl)acryloyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (MN5) (IC50= 16.71 ± 0.29 PtpA) and (2E)-6-(3-(3nitrophenyl)acryloyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (MN10) (IC50= 12.04 ± 1.90 for PtpB). The compound with better activity in relation to PtpB was MN10 and in relation to PtpA was MN5.