Relative molecular similarity in selected chemical carcinogens and the nucleoside triphosphate chain.
Several markers of cell toxicity are useful as screening tests for epigenetic carcinogens. The direct effects of chemicals on ATPase and GTPase function are pertinent to the early stages of carcinogenesis. Interference with triphosphate-diphosphate exchange mechanisms may result from the interaction of carcinogens with the substrate triphosphate chain. To investigate this hypothesis, a computational chemistry programme is used in this study to investigate molecular similarity in ATPase inhibitors, carcinogens and tumour promoters, in relation to the nucleoside triphosphate chain. The results show that atoms in the investigated molecular structures superimpose on sets of oxygen atoms in the triphosphate chain with interatomic distances < 0.3A. Relative molecular similarity to the substrate triphosphate chain is discussed in terms of the established inhibitory properties of carcinogens/tumour promoters on ATPase function, the carcinogen/ tumour promoting properties of ATPase inhibitors and the prediction of carcinogenic activity from chemical structure.
Williams
Wynford Robert
WR
School of Care Sciences, University of Glamorgan, Pontypridd CF37 1DL, UK. wrwillia@glam.ac.uk
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002273:Carcinogens / Q000737:chemistry* / Q000633:toxicity; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000633:toxicity; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009711:Nucleotides / Q000737:chemistry*; D013329:Structure-Activity Relationship
D002273:Carcinogens; D004791:Enzyme Inhibitors; D009711:Nucleotides; D000251:Adenosine Triphosphatases