Hові похідні гідразиду ізонікотинової кислоти як потенційні протитуберкульозні засоби

• Date: 2015
• Main Authors: Goncharenko, N. B., Blagodatnyi, V. V., Kovalishyn, V. V., Kopernyk, І. M., Kozachenko, O. P., Brovarets, V. S., Metelytsia, L. О.
• Format: Article
• Language: Ukrainian
• Published: National University of Pharmacy 2015
• Subjects: QSAR; Mycobacterium tuberculosis; H37RV; HR; похідні ізоніазиду; УДК 615.038; 579.873.21; 547.823/824
• Online Access: https://ophcj.nuph.edu.ua/article/view/ophcj.15.831
• Journal Title: Journal of Organic and Pharmaceutical Chemistry

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.