Abstract
New mutual prodrugs of pyrazinamide, isoniazid, p-aminosalicylic acid and ciprofloxacine were designed and synthesised. All the prepared compounds were tested for their antimycobacterial activities. Several discussed compounds showed excellent biological effects against both Mycobacterium tuberculosis and some atypical strains. These activities were comparable with or higher than those of the standards (pyrazinamide, isoniazid, rifampicin). These interesting compounds are presented here, and their physico-chemical properties are discussed. Stabilities of all the studied compounds were measured by means of RP-HPLC method simulating conditions of biological testing. Decomposition half-times of individual mutual prodrugs were determined. Experimentally found data were processed using the program MATLAB, reaction orders and rate constants were calculated. The experimental results were subsequently correlated with ab initio/ DFT calculations of electronic deficiency (δ+) in methine spacer connecting active parts of the molecule. The relationships between the chemical structure (π-electron density in the connecting CH linker) and the stability of the studied compounds are discussed.
Keywords: Antimycobacterials, Mutual prodrugs, Pyrazinamide, Isoniazid, Stability study, RP-HPLC, Mathematical modelling, Ab initio/DFT calculations
Current Organic Chemistry
Title: Study of Stability of New Mutual Prodrugs with Antimycobacterial Activity
Volume: 12 Issue: 8
Author(s): Josef Jampilek, Zuzana Reckova, Ales Imramovsky, Ivan Raich, Jarmila Vinsova and Jiri Dohnal
Affiliation:
Keywords: Antimycobacterials, Mutual prodrugs, Pyrazinamide, Isoniazid, Stability study, RP-HPLC, Mathematical modelling, Ab initio/DFT calculations
Abstract: New mutual prodrugs of pyrazinamide, isoniazid, p-aminosalicylic acid and ciprofloxacine were designed and synthesised. All the prepared compounds were tested for their antimycobacterial activities. Several discussed compounds showed excellent biological effects against both Mycobacterium tuberculosis and some atypical strains. These activities were comparable with or higher than those of the standards (pyrazinamide, isoniazid, rifampicin). These interesting compounds are presented here, and their physico-chemical properties are discussed. Stabilities of all the studied compounds were measured by means of RP-HPLC method simulating conditions of biological testing. Decomposition half-times of individual mutual prodrugs were determined. Experimentally found data were processed using the program MATLAB, reaction orders and rate constants were calculated. The experimental results were subsequently correlated with ab initio/ DFT calculations of electronic deficiency (δ+) in methine spacer connecting active parts of the molecule. The relationships between the chemical structure (π-electron density in the connecting CH linker) and the stability of the studied compounds are discussed.
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Jampilek Josef, Reckova Zuzana, Imramovsky Ales, Raich Ivan, Vinsova Jarmila and Dohnal Jiri, Study of Stability of New Mutual Prodrugs with Antimycobacterial Activity, Current Organic Chemistry 2008; 12 (8) . https://dx.doi.org/10.2174/138527208784577402
DOI https://dx.doi.org/10.2174/138527208784577402 |
Print ISSN 1385-2728 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5348 |
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