**ANTIINFLAMATORY AND ANTIMICOBACTERIAL ACTIVITY OF&NBSP; N-(ARYL)-2-THIOPHEN-2-YLACETAMIDE AGAINST MYCOBACTERIUM TUBERCULOSIS (MTB) AND MYCOBACTERIUM BOVIS (BCG)**

Fátima Maria Figueroa Vergara (FIOCRUZ); Andre Luis Peixoto Candéa (FIOCRUZ); Fausto Klabund Ferraris (FIOCRUZ); Marcus Vinícius Nora de Souza (FIOCRUZ); Maria das Graças Muller de Oliveira Henriques (FIOCRUZ)

Resumo

Tuberculosis killed approximately 1.6 million in 2005 alone, according to the latest estimates from the World Health Organization (WHO). Our group presented a new class of compounds and demonstrated its activity against Mycobacterium sp..Here we described the in vitro and in vivo effects of N-(aryl)-2-thiophen-2-ylacetamide against micobacteria infection. ਀㰀倀㸀吀栀攀搀椀爀攀挀琀最爀漀眀琀栀椀渀栀椀戀椀琀椀漀渀漀昀㰀䤀㸀䴀⸀ 戀漀瘀椀猀㰀⼀䤀㸀⸀ 眀愀猀攀瘀愀氀甀愀琀攀搀戀礀䄀氀愀洀愀爀戀氀甀攀㰀匀唀倀㸀글 㰀⼀匀唀倀㸀洀攀琀栀漀搀⸀ 吀栀攀戀愀挀琀攀爀椀愀猀甀猀瀀攀渀猀椀漀渀 ⠀㌀砀㄀　㰀匀唀倀㸀㘀㰀⼀匀唀倀㸀⼀眀攀氀氀⤀ 眀愀猀椀渀挀甀戀愀琀攀搀眀椀琀栀搀椀昀昀攀爀攀渀琀挀漀渀挀攀渀琀爀愀琀椀漀渀猀 ⠀　Ⰰ㄀㄀Ⰰ　㬀㄀　㬀㈀㔀㬀㄀　　딀最⼀洀䰀⤀ 漀昀琀栀攀挀漀洀瀀漀甀渀搀Ⰰ 昀漀爀㈀㐀栀猀⸀ 䌀椀琀漀琀漀砀椀挀椀琀礀漀昀琀栀攀挀漀洀瀀漀甀渀搀眀愀猀攀瘀愀氀甀愀琀攀搀戀礀䴀吀吀洀攀琀栀漀搀☀渀戀猀瀀㬀愀昀琀攀爀㐀㠀栀琀爀攀愀琀洀攀渀琀漀昀椀渀昀攀挀琀攀搀挀攀氀氀猀⸀ 䴀攀猀漀琀攀氀椀愀氀挀攀氀氀猀漀爀洀愀挀爀漀瀀栀愀最攀猀眀攀爀攀椀渀昀攀挀琀攀搀眀椀琀栀㰀䤀㸀䴀⸀ 戀漀瘀椀猀㰀⼀䤀㸀⠀㄀⼀㄀⤀ 愀渀搀琀爀攀愀琀攀搀昀漀爀㐀㠀栀猀⸀ 吀栀攀戀愀挀琀攀爀椀愀氀最爀漀眀琀栀眀愀猀挀漀甀渀琀攀搀㌀　搀愀礀猀愀昀琀攀爀戀攀攀渀挀甀氀琀椀瘀愀琀攀搀椀渀䰀漀眀攀渀猀琀攀椀渀䨀攀渀猀攀渀 ⠀䰀䨀⤀ 洀攀搀椀甀洀⸀ 䌀礀琀漀欀椀渀攀猀眀攀爀攀攀瘀愀氀甀愀琀攀搀戀礀䔀䰀䤀匀䄀愀猀猀愀礀愀渀搀渀椀琀爀椀挀漀砀椀搀攀 ⠀一伀⤀ 戀礀䜀爀攀椀猀猀洀攀琀栀漀搀Ⰰ 甀猀椀渀最猀甀瀀攀爀渀愀琀愀渀琀挀漀氀氀攀挀琀攀搀昀爀漀洀椀渀昀攀挀琀攀搀愀渀搀琀爀攀愀琀攀搀 ⠀㈀㐀栀猀⤀ 挀攀氀氀猀⸀ 吀爀愀渀猀氀漀挀愀琀椀漀渀漀昀一䘀ⴀ䈀昀愀挀琀漀爀眀愀猀愀渀愀氀礀稀攀搀戀礀挀漀渀昀漀挀愀氀洀椀挀爀漀猀挀漀瀀攀⸀ 一攀甀琀爀漀瀀栀椀氀愀搀栀攀猀椀漀渀眀愀猀椀渀瘀攀猀琀椀最愀琀攀搀甀猀椀渀最瀀氀愀琀攀搀洀攀猀漀琀栀攀氀椀愀氀挀攀氀氀猀 ⠀㄀　㰀匀唀倀㸀㐀㰀⼀匀唀倀㸀⼀眀攀氀氀⤀Ⰰ 椀渀昀攀挀琀攀搀愀渀搀琀爀攀愀琀攀搀琀栀攀洀眀椀琀栀琀栀攀挀漀洀瀀漀甀渀搀愀渀搀挀漀甀渀琀攀搀愀琀伀氀礀洀瀀甀猀䤀堀㜀　洀椀挀爀漀猀挀漀瀀攀愀渀搀愀渀愀氀椀猀攀搀愀琀䤀洀愀最攀䨀⸀ 吀栀攀攀砀瀀爀攀猀猀椀漀渀漀昀爀攀挀攀瀀琀漀爀猀眀愀猀愀渀愀氀礀稀攀搀戀礀昀氀漀眀挀礀琀漀洀攀琀攀爀⸀ 吀栀攀愀渀琀椀ⴀ椀渀昀氀愀洀洀愀琀漀爀礀愀渀搀琀栀攀愀渀琀椀洀椀挀漀戀愀挀琀攀爀椀愀氀攀昀昀攀挀琀㰀䤀㸀椀渀瘀椀瘀漀㰀⼀䤀㸀眀攀爀攀攀瘀愀氀甀愀琀攀搀椀渀䈀䌀䜀ⴀ椀渀搀甀挀攀搀瀀氀攀甀爀椀猀礀洀漀搀攀氀椀渀䌀㔀㜀䈀䰀⼀㘀洀漀甀猀攀 ⠀䌀䔀唀䄀Ⰰ 䘀椀漀挀爀甀稀㬀氀椀挀攀渀挀攀渀⸀ 䰀ⴀ　　　㐀⼀　㠀⤀Ⰰ 琀栀攀挀漀洀瀀漀甀渀搀眀愀猀愀搀洀椀渀椀猀琀爀愀琀攀搀椀渀琀爀愀瀀氀攀甀爀愀氀愀琀 ⠀　Ⰰ㔀ⴀ㔀　洀最⼀䬀最⤀⸀㰀⼀倀㸀

N-(aryl)-2-thiophen-2-ylacetamide wasn’t citotoxicity in both cells in all concentrations used. In vitro, this compound was able to inhibit directly the growth of MTB and BCG and the intracellular BCG growth. The treatment with the compound was able to reduce TNF-á, IL-6, Il-1â and nitric oxide in infected macrophages and decreased the translocation of NF-êB factor. The expression of mannose receptor was increased, indicating that this compound was able to modulate this phagositosis via. The expression of CD14 molecule was decreased in treated cells, indicating that this compound possibly interferes with the interaction between the receptor and the lipoarabinomanan and lipomanan. The compound affects neutrophil adhesion on mesothelial cells, possibly interfering in the cellular communication. Moreover the compound was able to decrease the liberation of IL-12 by mesothelial cells. In vivo treatment induced a decrease of total leukocyte, mononuclear, eosinophils and, especially neutrophils influx to the pleural cavity at the higher dose used (50mg/Kg). Also in vivo, we demonstrated that CD3⁺lymphocytes presented in pleural cavity increased the expression of IFN-ã and decreased the expression of IL-4 after treatment with the compound. Our data indicate that this new compound, N-(aryl)-2-thiophen-2-ylacetamide, presents in vitro and in vivo, an important antimicobacterial activity and immunomodulatory effect.

Palavras-chave: ANTIMICOBACTERIAL, ANTI-INFLAMMATORY, Mycobacterium tuberculosis, Mycobacterium bovis

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