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. 2020 Jul;15(10):869-879.
doi: 10.2217/fmb-2019-0085. Epub 2020 Jul 14.

Novel isoniazid derivative as promising antituberculosis agent

Galyna P Volynets  1 , Michail A Tukalo  2 , Volodymyr G Bdzhola  1 , Nataliia M Derkach  3 , Mykola I Gumeniuk  3 , Sergiy S Tarnavskiy  1 , Sergiy M Yarmoluk  1
Affiliations

Novel isoniazid derivative as promising antituberculosis agent

Galyna P Volynets et al. Future Microbiol. 2020 Jul.

Abstract

Background: A major focus of tuberculosis drug discovery is aimed at the development of novel antibiotics with activity against drug-resistant strains of Mycobacterium tuberculosis. Results: We have synthesized ten isoniazid derivatives and investigated for antibacterial activity toward M. tuberculosis H37Rv and isoniazid-resistant strain SRI 1369. It was revealed that only one compound, isonicotinic acid (1-methyl-1H-pyrrol-2-ylmethylene)-hydrazide (1), is active toward isoniazid-resistant strain with minimum inhibitory concentration value of 0.14 μM. This compound is not cytotoxic toward human liver cells (HepG2; IC50 >100 μM), demonstrates good permeability in Caco-2 cells. Accordingly to the results of plasma protein binding assay, unbound fraction of compound 1, which potentially exhibits pharmacologic effects, is 57.9%. Conclusion: Therefore, isonicotinic acid (1-methyl-1H-pyrrol-2-ylmethylene)-hydrazide is a promising compound for further preclinical studies.

Keywords: ADME properties; Mycobacterium tuberculosis; cytotoxicity; isoniazid derivative; isonicotinic acid (1-methyl-1H-pyrrol-2-ylmethylene)-hydrazide; multidrug-resistant tuberculosis.

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Conflict of interest statement

Financial & competing interests disclosure

This work was supported by the grant from the National Academy of Sciences of Ukraine (0117U003914). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

References

    1. Shakya N, Garg G, Agrawal B, Kumar R. Chemotherapeutic interventions against tuberculosis. Pharmaceuticals (Basel) 5(7), 690–718 (2012). - PMC - PubMed
    1. Somoskovi A, Bruderer V, Hömke R, Bloemberg GV, Böttger EC. A mutation associated with clofazimine and bedaquiline cross-resistance in MDR-TB following bedaquiline treatment. Eur. Respir. J. 45(2), 554–557 (2015). - PubMed

    2. •• Reports the first tuberculosis case infected by bedaquiline-resistant strain.

    1. Hoffmann H, Kohl TA, Hofmann-Thiel S et al. Delamanid and bedaquiline resistance in Mycobacterium tuberculosis ancestral Beijing genotype causing XDR-TB in a tibetian refugee. Am. J. Respir. Crit. Care Med. 193(3), 337–340 (2016). - PubMed
    1. Bloemberg GV, Keller PM, Stucki D et al. Acquired resistance to bedaquiline and delamanid in therapy for tuberculosis. N. Engl. J. Med. 373(20), 1986–1988 (2015). - PMC - PubMed
    1. Hartkoorn RC, Uplekar S, Cole ST. Cross-resistance between clofazimine and bedaquiline through upregulation of MmpL5 in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 58(5), 2979–2981 (2014). - PMC - PubMed

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