Study of Stability of New Mutual Prodrugs with Antimycobacterial Activity

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.