Synthesis and mutagenicity of trans-dihydrodiol metabolites of benzo[b]naphtho[2,1-d]thiophene.
The syntheses of potentially important metabolites of benzo[b]naphtho[2,1-d]thiophene ([2,1]BNT)--trans-1,2-dihydroxy-1,2-dihydrobenzo[b]naphtho[2,1- d]thiophene ([2,1]BNT-1,2-diol) and trans-3,4-dihydroxy-3,4-dihydrobenzo[b]naphtho[2,1-d]thiophene ([2,1]BNT-3,4-diol)--are described. The syntheses involved preparation of the appropriate 1-(3-benzo[b]-thiopheneyl)-2-(methoxyphenyl)ethylenes followed by photocyclization to methoxy-[2,1]BNTs, hydrolysis to hydroxy-[2,1]BNTs, oxidation to [2,1]BNT-diones, and NaBH4 reduction. The dihydrodiols were tested for mutagenicity in Salmonella typhimurium TA 100 with activation; [2,1]BNT-3,4-diol, which can form a bay region diol epoxide, was as mutagenic as [2,1]BNT whereas [2,1]BNT-1,2-diol was inactive. These results suggest that the metabolic activation of [2,1]BNT proceeds partially via formation of a bay region diol epoxide.
Misra
B
B
Division of Chemical Carcinogenesis, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York 10595.
Amin
S
S
D015197:Carcinogenicity Tests; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000633:toxicity; D009152:Mutagenicity Tests; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000378:metabolism* / Q000633:toxicity; D013876:Thiophenes / Q000138:chemical synthesis* / Q000378:metabolism* / Q000633:toxicity
D006571:Heterocyclic Compounds; D011083:Polycyclic Compounds; D013876:Thiophenes; C071513:1,2-dihydroxy-1,2-dihydrobenzo(b)naphtho(2,1-d)thiophene; C071512:3,4-dihydroxy-3,4-dihydrobenzo(b)naphtho(2,1-d)thiophene; C050001:benzo(b)naphtho(2,1-d)thiophene