Estudo de Inibidores da Anidrase Carbônica β da Mycobacterium tuberculosis por Modelagem Molecular e Análises de Componentes Principais e de Cluster

Resumo

Tuberculosis is caused by Mycobacterium tuberculosis. Although it is a treatable and curable disease, there are cases in which multidrugresistant strains emerge that are resistant to first- and second-line drugs used in treatment, leading to the need to identify new antibiotic candidates against this mycobacteriuM. Carbonic anhydrase (CA) is an essential enzyme for the metabolism of many living organisms. In humans, CA is of the α class, while in bacteria, it is of β class, making it a good candidate molecular target for the development of new antibiotics. In this study, a qualitative model was developed for classifying compounds of the sulfonamide class that showed inhibitory activity on bacterial CA. For this purpose, a comparative model for the 3D structure of M. tuberculosis CA was initially constructed, which was used in a molecular docking study with the sulfonamide series. Descriptors resulting from docking and descriptors of isolated molecules were combined with principal component and cluster analysis techniques to generate effective classification models of sulfonamides as inhibitors of M. tuberculosis carbonic anhydrase.