Modelagem molecular de uma série de compostos inibidores da enzima integrase do vírus HIV-1 / Molecular modelling for a series of integrase HIV-I inhibitors

AUTOR(ES)

Luciana Luzia de Carvalho

FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

20/07/2011

RESUMO

An essential step in the HIV life cycle is integration of the viral DNA into the host chromosome. This step is catalyzed by a 32-kDa viral enzyme HIV integrase (IN). HIV-1 IN is an important and validated target, and the drugs that selectively inhibit this enzyme, when used in combination with reverse transcriptase (RT) and protease (PR) inhibitors, are believed to be highly effective in suppressing the viral replication. IN catalyzes two discrete enzymatic processes referred as 3\ processing and DNA strand transfer. Agents active against HIV-1, which target the viral integrase by inhibiting the strand transfer step of integration, have now initialized the clinical trials. The Raltegravir® is the first drug in this new class. Clinical trials in treatment-experienced and in treatment-naive patients have shown that raltegravir-containing regimens have potent antiretroviral activity and are well tolerated. Given their potency, safety and novel mechanism of action, integrase inhibitors represent an important advance in HIV-1 therapy. In the present thesis, Bi- and Tridimensional Quantitative Structure-Activity Relationship (QSAR) studies were performed applying chemometric methods based on theoretical descriptors, Comparative Molecular Field Analysis (CoMFA) and Holograma QSAR (HQSAR) techniques, aiming to generate predictive models for a large set of HIV-1 IN inhibitors. QSAR models presenting good internal consistency, predictive power and stability were obtained in all cases. The final models along with the information resulted by 2D contribution and 3D contour maps should be useful in the design of new inhibitors with increased potency and selective within the chemical diversity of the data.

ASSUNTO(S)

comfa comfa docking molecular hiv-i hiv-i hqsar hqsar integrase integrase hiv-i molecular docking qsar qsar qsar-3d qsar-3d

Documentos Relacionados

• Estudo estrutura-atividade de alguns inibidores da enzima integrase do virus HIV-1
• Quantitative Structrure activity relationships for a series of HIV-1 protease inhibitors.
• Relation of HIV-I in bronchoalveolar lavage cells to abnormalities of lung function and to the presence of Pneumocystis pneumonia in HIV-I seropositive patients.
• Transmission of HIV-I from men to women in central Africa.
• Inhibitors of HIV-1 replication that inhibit HIV integrase.