Estudos de QSAR-3D para uma série de análogos à timidina com atividade tuberculostática


Tuberculosis (TB) is a chronic infectious disease with high epidemiological rates. The emergence of multidrug and extensively drug-resistant TB strains, as well as the long-term treatment and the side effects, become urgent the need for the development of new anti-tuberculosis drugs. Furthermore, the search for new targets is also necessary; as the current antimycobacterial drugs have just a small number of enzymes related to essential functions of the mycobacteria as targets. TMPKmt is an attractive target for the design of new antituberculosis agents since this enzyme is essential for DNA replication. In this work, we used the 3D-QSAR, by applying the Comparative Molecular Field Analysis (CoMFA), in order to elucidate the structural requirements relevant to the biological activity and to generate 3D-QSAR models for predicting the biological activity of compounds not yet synthesized, considering quantitative biological data and the interaction with TMPKmt of 106 thymidine analogues obtained from the literature. Robust and significant statistical models were obtained, confirming the importance of groups with higher electronic density and less bulky near ring 2. The studies herein developed with thymidine analogues through rational drug design lead to important data towards the search of new candidates as new anti-tuberculosis drugs.



QSAR-3D, Tuberculose, TMPK, Análogos de timidina, Tuberculostáticos potenciais, Potential tuberculostatic agents, Tuberculosis, Thymidine analogues


BUENO, Renata Vieira; BRAGA, Rodolpho Campos; TOLEDO, Ney Ramos; ANDRADE, Carolina Horta. Estudos de QSAR-3D para uma série de análogos à timidina com atividade tuberculostática. Revista da Universidade Vale do Rio Verde, Três Corações, v. 9, supl. 1, p. 8-13, 2011.