Bioorganic and Medicinal Chemistry Letters p. 4502 - 4505 (2005)
Update date:2022-08-28
Topics:
Sriram, Dharmarajan
Yogeeswari, Perumal
Madhu, Kasinathan
The purpose of this study was to prepare various isoniazid derivatives by introducing the isoniazid pharmacophore into several molecules and screening for antimycobacterial activity. Ortho-hydroxy acetophenone reacts with isoniazid to form acid hydrazones. The C-Mannich bases of the above acid hydrazones were prepared by reacting them with formaldehyde and various secondary amines. The synthesized compounds were screened against M. tuberculosis H37R v using the alamar blue susceptibility test. The synthesized compounds inhibit Mycobacterium tuberculosis strain H37Rv with minimum inhibitory concentrations ranging from 0.56 to 4.61 μM. Compound N′-{1-[2-hydroxy-3-(piperazin-1-ylmethyl)phenyl]ethylidene} isonicotinohydrazide 8 was found to be the most active compound with an MIC of 0.56 μM, and was more potent than isoniazid (MIC of 2.04 μM). After 10 days of treatment, compound 8 decreased the bacterial load in murine lung tissue by 3.7-log 10 as compared to controls, which was equipotent to isoniazid. The results demonstrate the potential and importance of developing new isoniazid derivatives against mycobacterial infections.
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