Biological Activity and Electronic Structure of the Aflatoxins

Heathcote, J. G.; Hibbert, J. R.

doi:10.1038/bjc.1974.99

Cited by 15 publications

(5 citation statements)

References 13 publications

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“…Comparison of the mutagenic activity of the tested aflatoxins and the presence of the 2,3-vinyl ether double bond in the terminal furan ring seems to support the involvement of this functional group in toxicologic action. Calculations of electronic structure also demonstrate the 2,3-double bond to be the most probable site of the K-region and hence the most susceptible to electrophilic attack (36).…”

Section: Discussionmentioning

confidence: 92%

Mutagenicity of aflatoxins related to their metabolism and carcinogenic potential.

Wong¹,

Hsieh²

1976

Proc. Natl. Acad. Sci. U.S.A.

222

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Aflatoxins and their animal biotransformation products were screened for carcinogenic potential using the Ames' in vitro microbial detection system for carcinogens as bacterial mutagens [B. N. Ames et aL (1973) Proc (1). The four naturally occurring AFs, aflatoxins B1 (AFB1), B2 (AFB2), G1 (AFG1), and G2 (AFG2), when administered as mixtures, were a potent class of animal hepatocarcinogens (2-6). They have been also associated with neoplastic formations in tissues and organs other than the liver (3,(6)(7)(8)(9).Tests with rats (10) and rainbow trout (11) have revealed that AFB1 is a potent hepatocarcinogen; AFG1 is also considerably carcinogenic, but AFB2 and AFG2 possess much lower activity. Recent studies on the metabolism of AFB1 have resulted in the isolation and identification of numerous metabolites, all of minor structural variations but significantly different biological activity relative to the parent compound (12).Among these metabolites, aflatoxins Q, (AFQ1), M1 (AFM1), Bk (AFBa), and P1 (AFP1), aflatoxicol (AFL), and aflatoxicol H1 (AFLH1) (Table 1) are the biotransformation products of AFB1 when the latter is incubated with liver preparations and a NADPH-generating system (13-17). Since evidence has indicated that AFB1 requires metabolic activation for its toxic, mutagenic, and/or carcinogenic activity (18)(19)(20)(21)(22), the toxicity of each metabolite has been of great interest in the search for the active molecular species. Attempts have been made to correlate the relative activity of the different metabolic pathways and the variations in the species susceptibility to aflatoxicosis (16,23 (24,25). The analysis of the known major AF metabolites in our study permits an observation of the structureactivity relationships as related to the carcinogenic potential of the AFs. MATERIALS AND METHODSChemicals are obtained as follows: AFBI, AFG1, AFB2, and AFG2 were purchased from Makor Chemicals, Ltd., Jerusalem, Israel. AFM1, AFQ1, and AFH1 were prepared by biotransformation of AFB1 using monkey liver homogenates (14, 17). AFL was prepared by a similar biotransformation method to be published elsewhere. AFB2k and AFGk were chemically synthesized from AFB1 with dilute acid (27). AFP1 was a chemically synthesized product kindly provided by G. N. Wogan, Massachusetts Institute of Technology, Cambridge, Mass. The purity and identity of all AFs was checked by fluorodensitometric analysis of thin-layer chromatography plates and mass spectrometry. In addition, AFQ1, AFM1, AFH1, and AFB2k were checked by high-pressure liquid chromatography (28). All biochemicals, NADP+, glucose 6-phosphate, histidine, and biotin, were purchased from Sigma Chemicals, St. Louis, Mo.The bacterial tester strain, Salmonella typhimurium strain TA 98 (21), was the generous gift of B. N. Ames, University of California, Berkeley. The bacteria were stored and grown as outlined by McCann et al. (21). The hepatic S-9 enzyme preparation was prepared from Charles River male white rats (200-250 g) and utilized according to procedur...

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Section: Discussionmentioning

confidence: 92%

Mutagenicity of aflatoxins related to their metabolism and carcinogenic potential.

Wong¹,

Hsieh²

1976

Proc. Natl. Acad. Sci. U.S.A.

222

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“…3) using the actual values and calibration set that gave a coefficient of determination (R 2 ) of 0.9911. The equation was Y = 0.9758x + 7.8432 [4] and the intercept and slope were not significantly different (P > 0.05) from 0.0 and 1.0, respectively. The calibration was evaluated by a set of known spiked samples.…”

Section: Methodsmentioning

confidence: 82%

“…Aflatoxin is a very potent acute poison to animals, humans included (4,5), although there are some differences in sensitivity between different species (3). In sublethal doses, it is a carcinogen, causing liver cancer in 10-20 yr. Because of its great danger, the food and livestock feed industries are wary of it and go to great lengths to detect it and reject any contaminated foodstuff.…”

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confidence: 99%

A new method for determining aflatoxins in groundnut and groundnut cake using fourier transform infrared spectroscopy with attenuated total reflectance

Mirghani

Man

Jinap

et al. 2001

J Americ Oil Chem Soc

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A new analytical method was developed for the determination of aflatoxins in groundnut and groundnut cakes by Fourier transform infrared (FTIR) spectroscopy using horizontal attenuated total reflectance technique. Groundnut and groundnut cake samples were used in this study. The wavelengths were selected for the four types of aflatoxins-B 1 , B 2 , G 1 , and G 2 -and the standards prepared for each by spiking some clean sample with the aflatoxins in concentrations of 0-1200 parts per billion. A partial least square regression was used to derive the calibration models for each toxin. The coefficients of determination (R 2 ) of the calibration model were computed for the FTIR spectroscopy predicted values vs. actual values of aflatoxins in parts per billion. The R 2 was found to be 0.9911, 0.9859, 0.9986, and 0.9789 for aflatoxins B 1 , B 2 , G 1 , and G 2 , respectively. Standard errors of calibration for groundnut samples were found to be 1.80, 2.03, 1.42, and 2.05 for aflatoxins B 1 , B 2 , G 1 , and G 2 , respectively. Calibration models were validated with an independent set of samples. The R 2 of validation models were computed. The SD of the difference for repeatability of the FTIR method was found to be better than that of the chemical method. Based on the results obtained, FTIR spectroscopy can be a useful instrumental method for determining aflatoxins in oilseeds and oilseed cakes. With its speed and ease of data manipulation by computer software, it is a possible alternative to the standard wet chemical methods for a rapid and accurate routine determination of aflatoxin levels in food and feed.Paper no. J9825 in JAOCS 78, 985-992 (October 2001).

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“…(i). Heathcote and Hibbert [ 34 ] determined the electronic structure of AFB 1 and its 4,19-dehydro derivative by the simple Hückel molecular orbital method to determine their structure–activity relationship. Hence, the molecular orbital calculations were expressed in terms of the bond order of the π-electrons.…”

Section: Resultsmentioning

confidence: 99%

Computational Studies of Aflatoxin B1 (AFB1): A Review

Martínez

Hernández-Rodríguez²,

Méndez‐Albores

et al. 2023

Toxins

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Aflatoxin B1 (AFB1) exhibits the most potent mutagenic and carcinogenic activity among aflatoxins. For this reason, AFB1 is recognized as a human group 1 carcinogen by the International Agency of Research on Cancer. Consequently, it is essential to determine its properties and behavior in different chemical systems. The chemical properties of AFB1 can be explored using computational chemistry, which has been employed complementarily to experimental investigations. The present review includes in silico studies (semiempirical, Hartree–Fock, DFT, molecular docking, and molecular dynamics) conducted from the first computational study in 1974 to the present (2022). This work was performed, considering the following groups: (a) molecular properties of AFB1 (structural, energy, solvent effects, ground and the excited state, atomic charges, among others); (b) theoretical investigations of AFB1 (degradation, quantification, reactivity, among others); (c) molecular interactions with inorganic compounds (Ag+, Zn2+, and Mg2+); (d) molecular interactions with environmentally compounds (clays); and (e) molecular interactions with biological compounds (DNA, enzymes, cyclodextrins, glucans, among others). Accordingly, in this work, we provide to the stakeholder the knowledge of toxicity of types of AFB1-derivatives, the structure–activity relationships manifested by the bonds between AFB1 and DNA or proteins, and the types of strategies that have been employed to quantify, detect, and eliminate the AFB1 molecule.

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Biological Activity and Electronic Structure of the Aflatoxins

Cited by 15 publications

References 13 publications

Mutagenicity of aflatoxins related to their metabolism and carcinogenic potential.

Mutagenicity of aflatoxins related to their metabolism and carcinogenic potential.

A new method for determining aflatoxins in groundnut and groundnut cake using fourier transform infrared spectroscopy with attenuated total reflectance

Computational Studies of Aflatoxin B1 (AFB1): A Review

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