Effect of various alkyl and unsaturated substituents on the mutagenicity of some nitrophenyl thioethers.
A variety of nitro-substituted phenyl alkyl/aryl thioethers and nitroso-substituted phenyl alkyl/aryl thioethers have been synthesized and tested for their mutagenicity towards Salmonella typhimurium strain TA100, TA98, TA98NR and TA98/1,8-DNP(6) in the absence of S9 mix. The relative order of mutagenicity in TA98 and TA100 among p-nitrophenyl thioethers having alkyl or aryl substituents is allyl>phenyl>benzyl>butyl>propyl>ethyl>methyl. Compounds having an alkyl chain C(6) to C(12) were found to be non-mutagenic. Among the various positional isomers (ortho, meta and para) of nitro-substituted diphenyl thioethers only the compounds having the -NO(2) function at the para position is mutagenic, whereas compounds having a -NO(2) function at ortho and meta are non-mutagenic. However, the reduced intermediate, ortho-nitroso derivative was found to be mutagenic in all the four strains but the meta-nitroso derivative was found to be non-mutagenic. All mutagens were found to be non-mutagenic when tested in nitroreductase deficient strain TA98NR, whereas their nitroso intermediates are found to be mutagenic. A substantial fall in the mutagenic activity is observed when some mutagens are tested in O-acetyltransferase deficient strain TA98/1,8-DNP(6).
Juneja
T R
TR
University Institute of Pharmaceutical Sciences, Punjab University, Chandigarh 160014, India.
Talukdar
A
A
Mehta
N
N
Gupta
R L
RL
D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D010647:Phenyl Ethers / Q000737:chemistry / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship; D013861:Thiocyanates / Q000737:chemistry / Q000633:toxicity*
D009153:Mutagens; D010647:Phenyl Ethers; D013861:Thiocyanates