Toxicity, mutagenicity, intracellular drug concentration and DNA binding in Escherichia coli treated with cis-platinum(II) complexes. 1987

H Razaka, and F Wimmer, and S Wimmer, and G Villani, and N P Johnson

The genotoxic effects of six cis-platinum(II)chloramine complexes with different alkyl substituents on their amine ligands have been measured using Escherichia coli. The toxicity and mutagenicity of these compounds were compared, after exposure of bacteria, to drug concentrations which gave known quantities of platinum-DNA lesions. The results permit several observations concerning structure-activity relations of platinum(II) complexes. Firstly, methyl substitution on the amine ligands of cis-diamminedichloro-platinum(II) (DDP) is reported to reduce its antitumor activity. The methyl group did not exert an effect in bacteria where the toxicity and mutagenicity of cis-bis(methylamine)dichloroplatinum(II) and DDP were equivalent. In fact, at equal levels of DNA binding, complexes with substituted amines were generally more toxic toward bacteria than DDP. Secondly, replacement of the chloro groups of DDP by nitrato ligands increased its toxicity and mutagenicity at a given level of DNA binding. Hence, although DDP and its dinitrato derivative have identical ammine ligands, they may form different platinum-DNA lesions in bacteria. Finally, cis-bis(cyclohexylamine)-dichloroplatinum(II) was unique among the compounds studied since it did not cause bacterial filamentation or mutagenesis. These results suggest that, although this compound binds to the bacterial genome, it may not induce the SOS response.

UI MeSH Term Description Entries
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D009944 Organoplatinum Compounds Organic compounds which contain platinum as an integral part of the molecule. Compounds, Organoplatinum
D010984 Platinum A heavy, soft, whitish metal, resembling tin, with atomic number 78, atomic weight 195.084, symbol Pt. It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". Platinum Black
D004269 DNA, Bacterial Deoxyribonucleic acid that makes up the genetic material of bacteria. Bacterial DNA
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

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