Molecular Diversity

, Volume 12, Issue 1, pp 47–59 | Cite as

Fragment-based and classical quantitative structure–activity relationships for a series of hydrazides as antituberculosis agents

  • Carolina H. Andrade
  • Livia de B. Salum
  • Marcelo S. Castilho
  • Kerly F. M. Pasqualoto
  • Elizabeth I. Ferreira
  • Adriano D. Andricopulo
Full Length Paper

Abstract

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, q2 = 0.68 and r2 = 0.72; HQSAR, q2 = 0.63 and r2  =  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, \({r^{2}_{pred} = 0.75}\)).

Keywords

Tuberculosis Infectious diseases Hydrazides Drug design QSAR 

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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Carolina H. Andrade
    • 1
  • Livia de B. Salum
    • 2
  • Marcelo S. Castilho
    • 3
  • Kerly F. M. Pasqualoto
    • 4
  • Elizabeth I. Ferreira
    • 1
  • Adriano D. Andricopulo
    • 2
  1. 1.Laboratório de Planejamento e Síntese de Quimioterápicos Potenciais Contra Endemias Tropicais, Faculdade de Ciências FarmacêuticasUniversidade de São PauloSão PauloBrazil
  2. 2.Laboratório de Química Medicinal e Computacional, Centro de Biotecnologia Molecular Estrutural, Instituto de Física de São CarlosUniversidade de São PauloSão CarlosBrazil
  3. 3.Laboratório de Bioinformática e Modelagem Molecular, Faculdade de FarmáciaUniversidade Federal da BahiaSalvadorBrazil
  4. 4.Laboratório de Quimiometria Teórica e Aplicada, Instituto de QuímicaUniversidade Estadual de CampinasCampinasBrazil

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