Research Article

Formation of N-Oxide metabolites from isoniazid hydrazones of substituted benzaldehydes by hepatic washed pig microsomal preparations

Volume: 27 Number: 1 June 28, 2025
Journal of Research in Pharmacy Cover
Journal of Research in Pharmacy
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Formation of N-Oxide metabolites from isoniazid hydrazones of substituted benzaldehydes by hepatic washed pig microsomal preparations

Abstract

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. It is highly transmissible through air droplets suspended in the air. Isoniazid has long been the first-choice drug for pulmonary and extra-pulmonary tuberculosis treatment and prophylaxis. It was first synthesized by Malley and Meyer in 1912. It is known that isoniazid is metabolized through hydrolysis, but there are less information on its metabolism into N-oxide metabolites in the presence of hydrazone structure. In this study, three different hydrazone structures ie 2-hydroxyphenyl, 4-methylphenyl and 4-bromophenyl derivatives were synthesized from the isoniazid with substituted aldehydes. Their purity were proven by chromatographic analysis. The potential N-oxide metabolites and the corresponding aldehyde hydrazones were synthesized and their structures were elucidated by spectroscopic methods. All the hydrazone derivatives were incubated with pig liver microsomal preparations fortified with NADPH. The formation of the metabolites were observed using LC-MS. The results indicated that 2-hydroxyphenyl and 4-methylphenyl derivatives produced N-oxide metabolite in the presence of enzyme and co-factors (NADPH) and 4-bromophenyl derivative produced N-oxide metabolite in the presence of enzyme but in the absence of co-factors. Hydrolysis was detected for only 4-methylphenyl and 4-bromophenyl derivatives (independently with enzyme and co-factor) but not with 2-hydroxyphenyl derivatives. These results indicated that the hydrazone derivatives might undergo metabolic oxidation reaction rather than hydrolytic reaction. The present study is the first example of N-oxide formation from hydrazide hydrazones bearing a pyridine ring.

Keywords

References

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Details

Primary Language

English

Subjects

Pharmaceutical Chemistry

Journal Section

Research Article

Authors

Publication Date

June 28, 2025

Submission Date

August 10, 2022

Acceptance Date

September 6, 2022

Published in Issue

Year 2023 Volume: 27 Number: 1

IZ

https://izlik.org/JA22XW97GW

Cite

RIS / Bibtex
APA
Coşkun, G., Algın, E. G., Karakoç, J. C., Türk Erbul, B., & Ülgen, M. (2025). Formation of N-Oxide metabolites from isoniazid hydrazones of substituted benzaldehydes by hepatic washed pig microsomal preparations. Journal of Research in Pharmacy, 27(1), 241-250. https://izlik.org/JA22XW97GW
AMA
1.Coşkun G, Algın EG, Karakoç JC, Türk Erbul B, Ülgen M. Formation of N-Oxide metabolites from isoniazid hydrazones of substituted benzaldehydes by hepatic washed pig microsomal preparations. J. Res. Pharm. 2025;27(1):241-250. https://izlik.org/JA22XW97GW
Chicago
Coşkun, Göknil, Elif Göksu Algın, Jülide Cansu Karakoç, Başak Türk Erbul, and Mert Ülgen. 2025. “Formation of N-Oxide Metabolites from Isoniazid Hydrazones of Substituted Benzaldehydes by Hepatic Washed Pig Microsomal Preparations”. Journal of Research in Pharmacy 27 (1): 241-50. https://izlik.org/JA22XW97GW.
EndNote
Coşkun G, Algın EG, Karakoç JC, Türk Erbul B, Ülgen M (June 1, 2025) Formation of N-Oxide metabolites from isoniazid hydrazones of substituted benzaldehydes by hepatic washed pig microsomal preparations. Journal of Research in Pharmacy 27 1 241–250.
IEEE
[1]G. Coşkun, E. G. Algın, J. C. Karakoç, B. Türk Erbul, and M. Ülgen, “Formation of N-Oxide metabolites from isoniazid hydrazones of substituted benzaldehydes by hepatic washed pig microsomal preparations”, J. Res. Pharm., vol. 27, no. 1, pp. 241–250, June 2025, [Online]. Available: https://izlik.org/JA22XW97GW
ISNAD
Coşkun, Göknil - Algın, Elif Göksu - Karakoç, Jülide Cansu - Türk Erbul, Başak - Ülgen, Mert. “Formation of N-Oxide Metabolites from Isoniazid Hydrazones of Substituted Benzaldehydes by Hepatic Washed Pig Microsomal Preparations”. Journal of Research in Pharmacy 27/1 (June 1, 2025): 241-250. https://izlik.org/JA22XW97GW.
JAMA
1.Coşkun G, Algın EG, Karakoç JC, Türk Erbul B, Ülgen M. Formation of N-Oxide metabolites from isoniazid hydrazones of substituted benzaldehydes by hepatic washed pig microsomal preparations. J. Res. Pharm. 2025;27:241–250.
MLA
Coşkun, Göknil, et al. “Formation of N-Oxide Metabolites from Isoniazid Hydrazones of Substituted Benzaldehydes by Hepatic Washed Pig Microsomal Preparations”. Journal of Research in Pharmacy, vol. 27, no. 1, June 2025, pp. 241-50, https://izlik.org/JA22XW97GW.
Vancouver
1.Göknil Coşkun, Elif Göksu Algın, Jülide Cansu Karakoç, Başak Türk Erbul, Mert Ülgen. Formation of N-Oxide metabolites from isoniazid hydrazones of substituted benzaldehydes by hepatic washed pig microsomal preparations. J. Res. Pharm. [Internet]. 2025 Jun. 1;27(1):241-50. Available from: https://izlik.org/JA22XW97GW