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KMID : 0043320030260100778
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Archives of Pharmacal Research
2003 Volume.26 No. 10 p.778 ~ p.784
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Synthesis, Antitubercular Activity and Pharmacokinetic Studies of Some Schiff Bases Derived from 1- Alkylisatin and Isonicotinic Acid Hydrazide (INH)
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Tarek Aboul-Fadl
Faragany Abdel-Hamid. Mohammed
Ehsan Abdel-Saboor Hassan
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Abstract
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N′-(1-alkyl-2,3-dihydro-2-oxo-1H-3-indolyliden)-4-pyridinecarboxylic acid hydrazide derivatives,3(a-g), were synthesized in a trial to overcome the resistance developed with the therapeutic uses of isoniazid (INH). The lipophilicity of the synthesized derivatives supersedes that of the INH as expressed by Clog p values. The synthesized compounds and INH were tested against bovin, human sensitive and human resist strains of Mycobacterium tuberculosis. Compounds3a, 3d, 3f and3g with 1-unsubstituted, 1-propyl, 1-propynyl and 1-benzyl groups respectively exhibited equipotent growth inhibitory activity (MIC 10 μmol) against the tested strains as compared with INH however the later has no activity against human resist strain. Pharmacokinetic study revealed that the rate and extent of absorption of the tested derivatives (3d and3f) significantly higher than that of INH (p<0.05). The relative bioavailabilities (FR%) were 183.15 and 443.25 for3f and3d respectively as compared to INH. These results preliminary indicate the possible use of the prepared derivatives for treatment of tuberculosis infections in order to overcome the resistance developed with INH.
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KEYWORD
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1-AlkylIsatin, Schiff bases, Lipophilicity, Antimycobacterial, In-vivo bioavailability, Relative bioavailability
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