New derivatives of isonicotinic acid hydraside as potential antitubercular agents

Authors

  • N. B. Goncharenko Clinicodiagnostic laboratory of the territorial medical Association "Phthisiology", Ukraine
  • V. V. Blagodatnyi Shupyk National Medical Academy of Postgraduate Education, Ukraine
  • V. V. Kovalishyn Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine
  • І. M. Kopernyk Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine
  • O. P. Kozachenko Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine
  • V. S. Brovarets Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine
  • L. О. Metelytsia Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine

DOI:

https://doi.org/10.24959/ophcj.15.831

Keywords:

QSAR, Mycobacterium tuberculosis, H37RV, HR, isoniazide derivatives

Abstract

The appearance of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb) is a stimulus for searching new and efficient antitubercular drugs. Despite the appearance of new antitubercular drugs, isoniazid is still the key and most effective component in all multitherapeutic regimens recommended by the WHO. This paper describes the QSAR design, synthesis and in vitro evaluation of the antitubercular activity of several potent isoniazid derivatives against Mtb strain (H37Rv) and resistant strain (HR). The QSAR method was applied using Artificial Neural Networks. The predictive ability of the regression model was estimated through leave-one-out cross-validation coefficient q2. The inhibition activities of 440 virtual compounds against Mtb were evaluated by the QSAR model developed, and seven isoniazid derivatives were selected and synthesized. In the biological research the multidrug-resistant strain of Mtb with resistance to isoniazid and rifampicin was used. All compounds synthesized with the predicted high activity showed antimycobacterial activity against Mtb strain H37Rv. “The compound-leader” – N1-(3-nitrophenylmethylidene)-pyridine-4-karbohidrazide revealing the activity against multiresistant strain (HR) of Mtb is identified as an original object for further research as an potential antimycobacterial agent.

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Published

2015-03-12

How to Cite

(1)
Goncharenko, N. B.; Blagodatnyi, V. V.; Kovalishyn, V. V.; Kopernyk І. M.; Kozachenko, O. P.; Brovarets, V. S.; Metelytsia L. О. New Derivatives of Isonicotinic Acid Hydraside As Potential Antitubercular Agents. J. Org. Pharm. Chem. 2015, 13, 59-62.

Issue

Vol. 13 No. 1(49) (2015)

Section

Original Researches

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Copyright (c) 2015 National University of Pharmacy

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