Synthesis and mutagenicity of the aflatoxin B1 model 3a,8a-dihydro-4,6-dimethoxyfuro[2,3-b]benzofuran and its 2,3-epoxy derivative

Turmo, Enric; Sánchez‐Baeza, Francisco; Bujons, Jordi; Camps, Francisco; Casellas, M.; Solanas, Anna M.; Messeguer, Ángel

doi:10.1021/jf00010a005

Cited by 5 publications

(3 citation statements)

References 12 publications

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“…Instead, a doublet of doublets centered at 5.42 ppm and a doublet at 4.19 ppm are present in this spectrum, which could be assigned to H-8 and H-9, respectively. As expected, H-8 showed an additional coupling with H-6a, which supported its identification (13). In addition, the acetal proton H-6a, which appeared as a singlet at 6.55 ppm in the parent mycotoxin, was split into a doublet centered at 5.70 ppm in the epoxide.…”

Section: Methodssupporting

confidence: 81%

“…of its reactivity (9,10) and cytotoxic activity on different biological matrices (11)(12)(13). The results obtained from these studies converged into considering AFBrE as a very potent mutagen and the main intermediate responsible for the cytotoxic effects elicited by the parent mycotoxin.…”

Section: Introductionmentioning

confidence: 68%

“…Solutions of dimethyldioxirane were prepared as described by Adam et al (16) and thoroughly dried over molecular sieves (3 Á). AFBi was from Aldrich Chemical Co. (Milwaukee, WI), and its 8,9-epoxide was prepared with dimethyldioxirane as previously described (13).…”

Section: Methodsmentioning

confidence: 99%

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Aflatoxin M1 8,9-Epoxide: Preparation and Mutagenic Activity

Bujons

Hsieh²,

Kado³

et al. 1995

Chem. Res. Toxicol.

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Treatment of aflatoxin M1 (AFM1) with dimethyldioxirane in an anhydrous mixture of CH2-Cl2 and acetone afforded the corresponding aflatoxin M1 8,9-epoxide (AFM1-E) in practically quantitative yield. This highly reactive intermediate was identified by 1H NMR and characterized by its neat conversion into the corresponding trans-methoxyhydrin derivative 1. The analysis of the 1H NMR spectrum of the above epoxide revealed that one stereoisomer, which should be that with the exo configuration, was present as major component. The mutagenicities of AFM1-E, the parent mycotoxin (AFM1), aflatoxin B1 (AFB1), and its epoxide (AFB1-E) were assessed by using a sensitive improved Ames test with the Salmonella typhimurium strain TA-100. AFM1 and AFB1 had specific mutagenic activities (SMA) of 13 and 121 revertants/ng, respectively, with S9 metabolic activation. AFM1-E was mutagenic with and without metabolic activation showing SMA of 13 and 12 revertants/ng, respectively. AFB1-E had a SMA of 42 and 29 revertants/ng, with and without S9 metabolic enzymes, respectively. These results suggest that the epoxidation of AFM1 can constitute a major route accounting for the cytotoxic effects elicited by this mycotoxin and that AFM1-E is not as active as AFB1-E in reacting with the constituents of the mutagenicity assay.

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Section: Methodssupporting

confidence: 81%