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1.
Arch Pharm (Weinheim) ; 357(2): e2300560, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38032154

RESUMO

Tuberculosis (TB) disease, caused by Mycobacterium tuberculosis (Mtb) is the leading cause of death among people with human immunodeficiency virus (HIV) infection. No dual-target drug is currently being used to simultaneously treat both infections. This work aimed to obtain new multitarget HIV-TB agents, with the goal of optimizing treatments and preventing this coinfection. These compounds incorporate the structural features of azaaurones as anti-Mtb and zidovudine (AZT) as the antiretroviral moiety. The azaaurone scaffold displayed submicromolar activities against Mtb, and AZT is a potent antiretroviral drug. Six derivatives were synthetically generated, and five were evaluated against both infective agents. Evaluations of anti-HIV activity were carried out in HIV-1-infected MT-4 cells and on endogenous HIV-1 reverse transcriptase (RT) activity. The H37Rv strain was used for anti-Mtb assessments. Most compounds displayed potent antitubercular and moderate anti-HIV activity. (E)-12 exhibited a promising multitarget profile with an MIC90 of 2.82 µM and an IC50 of 1.98 µM in HIV-1-infected T lymphocyte cells, with an 84% inhibition of RT activity. Therefore, (E)-12 could be the first promising compound from a family of multitarget agents used to treat HIV-TB coinfection. In addition, the compound could offer a prototype for the development of new strategies in scientific research to treat this global health issue.


Assuntos
Benzofuranos , Coinfecção , Infecções por HIV , HIV-1 , Mycobacterium tuberculosis , Tuberculose , Humanos , Coinfecção/tratamento farmacológico , Relação Estrutura-Atividade , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Antituberculosos/farmacologia , Antituberculosos/química , Infecções por HIV/tratamento farmacológico , Antirretrovirais/farmacologia
2.
J Virol Methods ; 219: 10-13, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25804245

RESUMO

Infection of pigs with swinepox virus (SWPV) was reported in Brazil in 2011. SWPV causes a systemic pustular disease in pigs and the symptoms are clinically indistinguishable from those caused by vaccinia virus (VACV) infection. Pigs infected with VACV have been reported in various countries; however, VACV is endemic in Brazil, India and other countries, where it affects mainly dairy cows, dairy buffaloes and dairy workers causing localized pustules. The transmission of VACV to other susceptible hosts has also been detected in Brazil. Therefore, VACV should be investigated as a possible etiologic agent of pustular skin disorders in pigs. This work describes the development of a one-step duplex assay to detect swinepox and vaccinia viruses simultaneously in skin lesions of pigs with generalized pustular disease. The investigation of VACV infection in pigs is important in countries where this zoonosis is endemic and should be differentiated from SWPV infection.


Assuntos
Reação em Cadeia da Polimerase , Infecções por Poxviridae/veterinária , Poxviridae/genética , Doenças dos Suínos/diagnóstico , Doenças dos Suínos/virologia , Vaccinia virus/genética , Vacínia/veterinária , Animais , DNA Viral , Sensibilidade e Especificidade , Suínos
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