Isonicotinic acid N -oxide, from isoniazid biotransformation by Aspergillus niger , as an InhA inhibitor antituberculous agent against multiple and extensively resistant strains supported by in silico docking and ADME prediction

Biotransformation of isoniazid produced isonicotinic acid ( isonicotinic acid -oxide ( ), and isonicotinamide which were isolated by column chromatography using silica gel and Sephadex LH 20 and elucidated using various spectroscopies. This is the first report for isolation of Antituberculosis activ...

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Bibliographic Details
Published in:Natural product research 2023-05, Vol.37 (10), p.1687-1692
Main Authors: Ragab, Amany E, Badawy, Ebtisam T, Aboukhatwa, Shaimaa M, Abdel-Aziz, Marwa M, Kabbash, Amal, Abo Elseoud, Kamilia A
Format: Article
Language:English
Subjects:
Antitubercular Agents - chemistry
Antitubercular Agents - pharmacology
Aspergillus niger - metabolism
Bacterial Proteins - metabolism
Bioavailability
Biotransformation
Column chromatography
Docking
Drug resistance
Hepatotoxicity
Isoniazid
Isoniazid - chemistry
Isoniazid - metabolism
Isoniazid - pharmacology
Isonicotinic Acids - metabolism
Microbial Sensitivity Tests
Multidrug resistance
Mycobacterium tuberculosis
Oxides
Pharmacokinetics
Reductases
Silica
Silica gel
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Summary:Biotransformation of isoniazid produced isonicotinic acid ( isonicotinic acid -oxide ( ), and isonicotinamide which were isolated by column chromatography using silica gel and Sephadex LH 20 and elucidated using various spectroscopies. This is the first report for isolation of Antituberculosis activity was evaluated against strains: drug sensitive (DS), multiple drug resistant (MDR) and extensively drug resistant (XDR). and isoniazid showed MICs of 63.49, 0.22, 15.98 and 0.88 µM, respectively, against the DS strain. For the MDR strain, and exhibited MICs of 28.06 and > 1000 µM, respectively, while was inactive. Moreover, had an MIC of 56.19 µM against XDR strain, while and were inactive. Docking simulation using enoyl ACP reductase (InhA) revealed favorable protein-ligand interactions. study of pharmacokinetics and hepatotoxicity predicted to have good oral bioavailability and to have a lower hepatoxicity probability than isoniazid.
ISSN:1478-6419
1478-6427
DOI:10.1080/14786419.2022.2103695