Evaluation of genotoxity and mutagenicity of DL-p-chlorophenylalanine, itsmethyl ester and some N-acyl derivatives

DL-p-chlorophenylalanine (PCPA) and its derivatives were evaluated for geno toxic effects using Escherichia coli and Bacillus subtilis strains lacking various DNA-repair mechanisms in spottest and in suspension test. The mutag enic activity of studied compounds was determined by the Ames test. Reverse mutation test was performed with Salmonella typhimurium strains TA98, TA10 0, TA1535 and TA1537 without S9 mix. 0.02 M nitrosomethylurea (NMU) standar d mutagen was used as a positive control, The results showed that the paren t nonessential amino acid PCPA had no detectable genotoxic and mutagenic ac tivities in bacteria. The methyl ester of this amino acid and its N-phenyla cetyl derivative possessed weak genotoxicity. Meanwhile N-sec-butyloxycarbo nyl, N-benzyloxycarbonyl, N-(p-nitrophenylacetyl) and N-(p-nitrophenoxyacet yl) derivatives of DL-p-chlorophenylalanine exhibited appreciable genotoxic ity. Among the seven tested compounds only N-benzyloxycarbonyl and N-(p-nit rophenoxyacetyl) derivatives of DL-p-chlorophenylalanine have been found to be mutagenic. Only parent PCPA possessed antimutagenic properties in respe ct of nitrosomethylurea. The structural modification, which strongly affect s genotoxicity and mutagenicity perhaps may be due to steric hydrance of th e substituents, causing interference with enzyme and DNA interactions.