Synthesis of isoniazid from citric acid - Wiley Online …

Isoniazid is one of the widely used first-line drugs in the treatment of tuberculosis for many years but the mechanism of the action of the drugs is still not clear. Herein, we report the synthesis, QSAR model study and biological effects of esters and thioester derivative of isonicotinic acid (INA) on different strains of Mycobacterium tuberculosis in an attempt to establish the mode of action of the active form of Isoniazid (INH). The esters of INA are expected to show antibiotic activities against strains of Mycobacterium tuberculosis upon activation by intracellular nonspecific esterases, while thioesters is expected not to show antimicrobial effects and thus served as control. The obtained results indicated that the synthesized esters did not show antimicrobial activity. The conclusion drawn from the result is that either INA is not the active form of INH or that the esters show poor water solubility- in addition to the possibility of acquired during resistance of the strains during culture and testing - all of which could hamper mycobacterial cell up take. This suggests that more studies are needed to search for the possible active form of isoniazid.

Isoniazid is oxidized by activated ..

Hypochlorous acid was also able to oxidize isoniazid to isonicotinic acid

At therapeutic levels isoniazid …

A series of isonicotinic acid hydrazide derivatives (119) was synthesized and tested in vitro for antimycobacterial activity against Mycobacterium tuberculosis and antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Candida albicans, and Aspergillus niger and the results indicated that the compounds with OH, SCH3, and OCH3 groups were found to be active against the tested strains. None of the test compounds were active against a broad variety of RNA and DNA viruses at subtoxic concentrations, except 8, that showed some selective anti-reovirus-1 activity. The multi-target QSAR models were found to be effective in predicting the antimicrobial activity of the isoniazid derivatives and indicated the importance of nuclear repulsion energy (Nu.E) in explaining the antimicrobial activity of isoniazid derivatives. The developed QSAR models were validated using the external test set of synthesized derivatives.

General procedure for the synthesis of isonicotinic acid hydrazide

A series of isonicotinic acid-1-(substituted phenyl)-ethylidene/cycloheptylidene hydrazide derivatives (112) was tested for their, in vitro antimycobacterial activity against Mycobacterium tuberculosis, and compound 2 was found to be more active than isoniazid. The antiviral screening results indicated that none of the tested compounds was active against a broad variety of DNA and RNA viruses at subtoxic concentrations, except compounds 8 and 10 that proved to be active against DNA viruses at concentrations close to their cytostatic potential. The synthesized compounds were also screened for their antimicrobial potential against S. aureus, B. subtilis, E. coli, C. albicans and A. niger, and the results indicated that compounds having Br, OCH3 and Cl groups were highly active. The multi-target QSAR models indicated the importance of lipophilic (log P) and topological parameters (3χv) in describing the antimicrobial activity.

Karaoglu SA (2009a) Synthesis of some new 1,2,4-triazoles starting from isonicotinic acid hydrazide and evaluation of their antimicrobial activities
The present invention relates to a process for the synthesis of isonicotinic acid hydrazide. More particularly, the present invention relates to a process for the synthesis of isonicotinic acid hydrazide(INH) from isonicotinamide. Isonicotinic acid hydrazide (INH) is used in the treatment of tuberculosis. Background of the invention.

Isonicotinic acid hydrazide or isoniazid (INH, ..

Due to the high resistance of Mtb in the hospitals caused by inappropriate treatment administration, it has become necessary to search for isoniazid’s derivatives that are probable intermediate responsible for its biological activity. This probable intermediate which is synthesized derivatives is therefore expected to be potent enough to kill this micro-organism (Mtb). Ester and thioester are the active forms of isonicotinic acid (INA) that can be generated under different condition (Figure 1) [3].

22/12/2017 · BAIZER.M.M.; DUB.M.; GISTER.S.; STEINBERG.N.G., 1956: Synthesis of isoniazid from citric acid

Authors; Authors and affiliations; Vikramjeet Judge; ..

Isoniazid (Isonicotinic acid hydrazide) is the most commonly used drug for active infection and prophylaxis since its introduction for treatment of TB in 1952. Isoniazid is a prodrug that is activated by Kat G, the mycobacterial catalase-peroxidase. The activated form of isoniazid forms a covalent complex with an acyl carrier protein (AcpM) and Kas A, a beta-ketoacyl carrier protein synthetase, which blocks mycolic acid synthesis. 9 Enzymatic acetylation of INH in human beings greatly reduces its therapeutic activity resulting in under dosing, decreased bioavailability and acquired INH resistance. Chemical modification of INH with a functional group that blocks acetylation, while maintaining strong antimycobacterial action, may improve clinical outcomes and help to reduce the rise of INH resistance.

Isonicotinic acid hydrazide derivatives: synthesis, antimicrobial activity, and QSAR studies

Jain S, Tilekar A, Upadhayaya RS, Kishore N, Jana GH, Arora …