Synthesis and Antimycobacterial Activity of a Novel Series of Isonicotinylhydrazide Derivatives

Abstract

A novel series of 14 new isonicotinyl hydrazide derivatives 2a-g, 3a-g containing a 4-thiazolidinone / 2-azetidinone nucleus were synthesized by reacting N'-substituted arylidene / heteroarylidene isonicotinyl hydrazide 1a-g with thioglycollic acid in the presence of dry benzene and with chloroacetyl chloride in the presence of triethylamine, respectively. Structures of all newly synthesized compounds were characterized on the basis of elemental analyses and spectral data (IR and (1)H-NMR). All the title compounds were tested for their in-vitro antimycobacterial activity against Mycobacterium tuberculosis H(37)Rv using Alamar-Blue susceptibility test, and the activity is expressed as the minimum inhibitory concentration (MIC) in microg/mL. Among the series, compounds 2b, 2g, 3b, and 3g displayed an encouraging antimycobacterial activity profile as compared to that of the reference drugs isoniazid / rifampicin.

Indole-based hydrazide-hydrazones and 4-thiazolidinones: synthesis and evaluation as antitubercular and anticancer agents

“…In the search for effective and selective antitubercular agents, we achieved the synthesis of novel hydrazone (6) and 4-thiazolidinone (7,8) derivatives of the 5-fluoro-3-phenyl-1H-indole scaffold. All the newly synthesized compounds (6)(7)(8) were evaluated for in vitro anti-TB activity against M. tuberculosis H37Rv.…”

“…All the newly synthesized compounds (6)(7)(8) were evaluated for in vitro anti-TB activity against M. tuberculosis H37Rv. The 4-thiazolidinone derivatives 7g-7j, 8g, 8h and 8j displayed appreciable anti-TB activity showing 99% inhibition at MIC values ranging from 25.0 to 6.25 mg/ml along with rather low cytotoxicity against mammalian cell lines.…”

“…The novel indolylhydrazones (6) and indole-based 4-thiazolidinones (7,8) were tested for in vitro antitubercular activity against M. tuberculosis H37Rv using the BACTEC 460TB system [31][32][33] . The antituberculosis (anti-TB) drug, rifampicin, was used as the positive control.…”

“…An early representative actithiazic acid, (À)-2-(5-carboxypentyl)thiazolidin-4-one (Figure 1), isolated from the culture broth of a strain of streptomyces shows highly specific in vitro activity against MTB 4,5 . 2-Arylhydrazono-4-oxo-3-phenyl-5-thiazolidinone acetic acids 6 , piperidone based 1,3-thiazolidin-4-ones 7 , isonicotinyl hydrazide derivatives containing the 4-thiazolidinone nucleus 8 and numerous different 2,3-disubstituted or 2,3,5-trisubstituted 4-thiazolidinones [9][10][11] have been reported to possess appreciable in vitro antitubercular activity. Likewise, spirothiazolidinone featured molecules, N-alkyl substituted spirothiazolidinones 13 , spirothiazolidinones bearing the imidazo [2,1-b]thiazole residue 14 and indole-2-carboxamides with a spirothiazolidinone moiety 15 , have been found to be effective as growth inhibitors of MTB.…”

A Review on Potent Antitubercular Agent Isoniazid and Its Analogues

“…Isoniazid also isoniazidibits mycobacterial catalase-peroxidase (the isoniazid-activating enzyme), which may increase the possibility of damage to mycobacteria from reactive oxygen species. [60][61][62][63] The main excretory products in humans result from enzymatic acetylation (acetylisoniazid) and enzymatic hydrolysis (isonicotinic acid). Small quantities of an isonicotinic acid conjugate (probably isonicotinyl glycine), one or more isonicotinyl hydrazones, and traces of N-methylisoniazid also are detectable in the urine.…”