Fragment-based and classical quantitative structure-activity relationships for a series of hydrazides as antituberculosis agents.
Worldwide, tuberculosis (TB) is the leading cause of death among curable infectious diseases. Multidrug-resistant Mycobacterium tuberculosis is an emerging problem of great importance to public health, and there is an urgent need for new anti-TB drugs. In the present work, classical 2D quantitative structure-activity relationships (QSAR) and hologram QSAR (HQSAR) studies were performed on a training set of 91 isoniazid derivatives. Significant statistical models (classical QSAR, q (2) = 0.68 and r (2) = 0.72; HQSAR, q (2) = 0.63 and r (2) = 0.86) were obtained, indicating their consistency for untested compounds. The models were then used to evaluate an external test set containing 24 compounds which were not included in the training set, and the predicted values were in good agreement with the experimental results (HQSAR, r(2)(pred) = 0.87; classical QSAR, r(2)(pred) = 0.75).
Andrade
Carolina H
CH
Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Av. Professor Lineu Prestes 580, 05508-900, São Paulo, SP, Brazil.
Salum
Livia de B
Lde B
Castilho
Marcelo S
MS
Pasqualoto
Kerly F M
KF
Ferreira
Elizabeth I
EI
Andricopulo
Adriano D
AD
D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology*; D007538:Isoniazid / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
D000995:Antitubercular Agents; D007538:Isoniazid