Novel Isoniazid Derivative as Promising Antituberculosis Agent

Volynets, Galyna P.; Tukalo, M. A.; Bdzhola, Volodymyr G.; Derkach, N. M.; Gumeniuk, Mykola; Tarnavskiy, S. S.; Yarmoluk, S. M.

doi:10.2217/fmb-2019-0085

Cited by 12 publications

(6 citation statements)

References 33 publications

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“…MRC-cell (normal human fetal lung fibroblasts) was selected because it is widely used for the phenotypic screening of compounds and J774A.1, a mice macrophage original cell line. This cell is usually used to determine the inhibition of intracellular pathogens and, because of the incubation time of the intramacrophagic experiment, it was tested for up to 72 h [ 25 , 26 ].…”

Section: Resultsmentioning

confidence: 99%

Latent Tuberculosis: A Promising New Compound to Treat Non-Replicating and Intramacrophagic Mycobacteria

et al. 2022

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As a biologic reservoir of Mycobacterium tuberculosis (M. tb), one-quarter of the world population is infected with the well-known latent tuberculosis (LTBI). About 5–10% of LTBI patients will progress to active disease in the first years after primary infection and, despite using the recommended treatment, 20% can still reactivate the infection. A new LTBI treatment could minimize adverse effects and antibiotic resistance that can occur when the same drug is used to treat the latent and active disease. New hydrazones were evaluated, and they showed great inhibitory activity against intramacrophagic and non-replicating M. tb, commonly found at this stage of infection, in addition to bactericidal and narrow-spectrum activity. When tested against eukaryotic cells, the hydrazones showed great safety at different exposure times. In vitro, these compounds performed better than isoniazid and could be considered new candidates for LTBI treatment, which may promote greater engagement in its prescription and adherence.

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Section: Resultsmentioning

confidence: 99%

Latent Tuberculosis: A Promising New Compound to Treat Non-Replicating and Intramacrophagic Mycobacteria

et al. 2022

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“…Compound 1-methyl-1H-pyrrol-2-ylmethylene)-hydrazide (90) (Fig. 25 ) has shown inhibitory activity toward isoniazid-resistant strain with IC 50 of 0.14 μM [ 161 ]. Shiva Raju et al [ 162 ] also reported 1 H -pyrrolo[2,3-d]pyrimidine-1,2,3-triazole analogs as novel anti-tubercular agents.…”

Section: Antimycobacterial Agentsmentioning

confidence: 99%

Therapeutic potential of pyrrole and pyrrolidine analogs: an update

Basha¹,

Basavarajaiah²,

Shyamsunder³

2022

Mol Divers

102

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The chemistry of nitrogen-containing heterocyclic compound pyrrole and pyrrolidine has been a versatile field of study for a long time for its diverse biological and medicinal importance . Biomolecules such as chlorophyll, hemoglobin, myoglobin, and cytochrome are naturally occurring metal complexes of pyrrole. These metal complexes play a vital role in a living system like photosynthesis, oxygen carrier, as well storage, and redox cycling reactions. Apart from this, many medicinal drugs are derived from either pyrrole, pyrrolidine, or by its fused analogs. This review mainly focuses on the therapeutic potential of pyrrole, pyrrolidine, and its fused analogs, more specifically anticancer, anti-inflammatory, antiviral, and antituberculosis. Further, this review summarizes more recent reports on the pyrrole, pyrrolidine analogs, and their biological potential. Graphical Abstract

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“…Among the series, compounds 3a-f, 4, 5 and 6 were found active showing sensitivity towards growth inhibition of H37Rv strain of M. tb [9]. A series of isoniazid derivatives were synthesized evaluated for anti-TB activity against the drug resistant strains of M. Tb by Volynets et. al.…”

Section: Introductionmentioning

confidence: 99%

“…The compounds were found to be active with the MIC values ranging 0.4-42 µM. Among the series the most active compound 7 showed MIC = 0.4 µM against virulent strain (H37Rv) whereas MIC = 0.14 µM against INH-Resistant strain [20]. Patil et.…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Isonicotinoylhydrazonobutanoic acidderivatives as anti-tubercular agents: In-silico studies, synthesis, spectral characterization and biological evaluation.

Lone

Mubarak

Nabi

et al. 2022

Preprint

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A series of novel 4-(2-isonicotinoylhydrazono) butanoic acid derivatives (3a-n) were designed, synthesized and evaluated for anti-tubercular activity. The synthesized compounds were characterized by 1H-NMR, 13C-NMR, FT-IR, and Mass Spectroscopic analyses. The synthesized compounds were evaluated for anti-mycobacterial activity against avirulent (H37Ra), virulent (H37Rv) as well as INH-Resistant strains that showed good to moderate activity. The MIC and MBC values observed were found identical for both H37Ra and H37Rv. 3a, 3c, 3e and 3i were found as the most potent in the series with a MIC and MBC = 1µg/ml. The compounds showed moderate activity against the INH-resistant clinical isolates as well. The potent compounds 3a, 3c and 3i showed least cytotoxicity towards normal human cell lines (HEK-293, AML12 and RAW-264). Molecular docking studies of the synthesized compounds performed with the protein target M. tuberculosis InhA in complex with NADH (PDB ID: 4DRE) revealed that compound 3c showed the best dock score of -7.798. The compound 3c forms two hydrogen bonds with Valine (VAL 65) and Serine (SER 20) whereas INH forms two hydrogen bonds with Valine (VAL 65) and Glycine (GLY 96). Both the benzene ring and pyridine ring of the compound 3c displayed the π-π interactions with Phenylalanine (PHE 41). Physicochemical properties and pharmacokinetic profiling assessed for the synthesized compounds were found to follow Lipinski’s rule using Swiss ADME online prediction tools. These findings make them promising candidates for the future development of new anti-tubercular agents.

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Novel Isoniazid Derivative as Promising Antituberculosis Agent

Cited by 12 publications

References 33 publications

Latent Tuberculosis: A Promising New Compound to Treat Non-Replicating and Intramacrophagic Mycobacteria

Latent Tuberculosis: A Promising New Compound to Treat Non-Replicating and Intramacrophagic Mycobacteria

Therapeutic potential of pyrrole and pyrrolidine analogs: an update

WITHDRAWN: Isonicotinoylhydrazonobutanoic acidderivatives as anti-tubercular agents: In-silico studies, synthesis, spectral characterization and biological evaluation.

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