Test of chiral recognition in the salmonella typhimurium (TA100) mutagenicity of mucochloric acid‐cysteine adducts

Abstract

A difference in biological response to enantiomers is not an uncommon observation and is, therefore, to be expected in various manifestations of genotoxicity. The bacterial mutagen mucochloric acid (2,3-dichloro-5-hydroxy-2(5H)-furanone) has one chiral center, at C-5, but this mutagen exists in racemic form because of the facile stereoisomerization occurring by the mechanism of ring-chain tautomerism. Two readily synthesized enantiomeric analogs of mucochloric acid, as well as the racemic form of the two, were prepared from mucochloric acid and (R)-(+)-, (S)-(-)-, and (R,S)-(+/-)-cysteine. Using Salmonella typhimurium (TA100), the enantiomeric compounds were assayed together in four dose/response assays along with mucochloric acid, the reference mutagen. In three of the same four assays, the racemic form was also assayed. Neither statistically significant differences in mutagenicity, as determined in slope responses, nor distinctions from the plotted curves were observed among the two enantiomers and their racemic form. Therefore, no enantiospecific interaction between enantiomers and chiral DNA or enzymes involved in repair or replication could be concluded.

Hologram Quantitative Structure Activity Relationship (HQSAR) Study of Mutagen X

“…As a result, the resultant MX analogs show wide range of mutagenicity. [21][22][23][24][25][26][27][28][29][30][31][32][33][34] They are modeled by structure-activity relationship methods. [35][36][37] In spite of this multitude of studies, basic questions concerning the nature of the reactive species and the mechanism of interaction of these compounds with DNA to produce their remarkable mutagenic potency in SAL TA100 remain unresolved.…”

“…At a glance, as the degree of chlorine or bromine substitution increases, the mutagenicity also increases. The compounds collected from the various reports [21][22][23][24][25][26][27][28][29][30][31][32][33][34] are categorized into three groups as shown in . This open family has never been explicitly included in the previous QSAR studies.…”