The new inhibitors of ribonucleotide reductase--comparison of some physico-chemical properties.
Amidox (AX), didox (DX) and trimidox (TX), compounds synthetized as new ribonucleotide reductase inhibitors, have been investigated by ultraviolet (UV) spectrophotometry, polarography and high performance liquid chromatography (HPLC). The experiments have been performed at various pH values. The changes in UV absorption of the compounds studied were recorded and it was demonstrated that these changes are related to the pH and to structural features of the investigated molecules. From the compounds included in our series of experiments, only amidox and trimidox are reduced during polarographic experiments in Britton-Robinson buffer. The reduction of both compounds proceeded in two one-electron steps in acidic pH. One two-electron diffuse irreversible wave was observed at basic pH. The values of the half-wave potential became more negative in accordance with the increasing pH. HPLC assay also showed changes in the retention of compounds investigated, particularly when the pH of the mobile phase was close to the dissociation constant of the particular drug. The changes of physico-chemical properties detected by the all used methods are related to different chemical structures (the most significant changes were observed in alkaline pH).
Romanova
D
D
Cancer Research Institute Slovak Academy of Sciences, Bratislava, Slovak Republic.
Vachalkova
A
A
Szekeres
T
T
Elford
H L
HL
Novotny
L
L
D001550:Benzamidines / Q000737:chemistry* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology; D010091:Oximes / Q000737:chemistry* / Q000494:pharmacology; D011048:Polarography; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D013056:Spectrophotometry, Ultraviolet
C074761:3,4,5-trihydroxybenzamidoxime; D001550:Benzamidines; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D010091:Oximes; C070491:Amidox; D012264:Ribonucleotide Reductases; C035419:3,4-dihydroxybenzohydroxamic acid