Exposure to mycotoxins, secondary metabolites produced by fungi, may infer serious risks for animal and human health and lead to economic losses. Several approaches to reduce these mycotoxins have been investigated such as chemical removal, physical binding, or microbial degradation. This review focuses on the microbial degradation or transformation of mycotoxins, with specific attention to the actual detoxification mechanisms of the mother compound. Furthermore, based on the similarities in chemical structure between groups of mycotoxins and environmentally recalcitrant compounds, known biodegradation pathways and degrading organisms which hold promise for the degradation of mycotoxins are presented.

https://biblio.ugent.be/publication/7221223/file/7253652.pdf

Biodegradation of Mycotoxins: Tales from Known and Unexplored Worlds.

Aflatoxin B1 (AFB1) widely contaminates staple food and feed crops and is well-known as the most potent natural hepatocarcinogen in humans and domesticated animals. This review highlights significant advances in our understanding of the pivotal role of phase I and II metabolizing enzymes in the bioactivation and detoxification of AFB1 and its metabolites across species. In humans, cytochrome P450 (CYP) 1A2, CYP3A4, CYP3A5, and CYP3A7 in liver and CYP2A13 in lung are essential for the bioactivation of AFB1 to the extremely toxic exo-AFB1-8,9-epoxide (AFBO), whereas CYP1A1, CYP1A2, CYP2A6, and CYP3A4 are important in the turkey and duck, CYP1A1 and CYP2A6 are important in the chicken and quail, CYP3A11 and CYP3A13 are important in mice, and CYP2A5 are important in the hamster. In contrast, glutathione-S-transferase (GST) M1 and GSTT1 are primary responsible for detoxification of the AFB1 by catalyzing the conjugation of GSH to AFBO in humans, whereas GSTM2 in a nonhuman primate, GSTA3 in mice, GSTA5 in rats, and GSTA1, GSTA2, GSTA3 and GSTA4 in the turkey are important. Additionally, microsomal epoxide hydrolase (mEH) and aflatoxin-aldehyde reductase (AFAR) have also been shown to play key roles in AFB1 detoxification in the human, rat, and pig. Moreover, an overview of the chemoprotective agents, including synthetic compounds and naturally occurring plant compounds, which can be used to reduce aflatoxicosis is provided based on their ability to regulate these key enzymes. Collectively, this review summarizes the pivotal enzymes in the metabolism of AFB1 among humans, experimental and farm animals, as well as the chemoprotective agents that can be used to minimize risk of aflatoxicosis.

Aflatoxin B1 metabolism: Regulation by phase I and II metabolizing enzymes and chemoprotective agents.

Editorial:

In the present editorial, Quantitative Structure Activity Relationship (QSAR) and Quantitative Structure Properties Relationship (QSPR) equations were derived using the algorithm of the partition coefficient for the cancer risk prediction and assessment in human cells under synchrotron radiations. Further mixed surfactant systems of an anionic surfactant and several non-ionic surfactant of different hydrophobic chain lengths were taken together to calculate the parameters [1-22]. Quantitative Structure Activity Relationship (QSAR) and Quantitative Structure Properties Relationship (QSPR) equations under synchrotron radiations were developed from the surface tension data to predict cancer risk assessment in human cells and compared with Quantitative Structure Activity Relationship (QSAR) and Quantitative Structure Properties Relationship (QSPR) derived values to understand probable mechanisms of action of the mixed surfactants blends for aquatic toxicity. The established Quantitative Structure Activity Relationship (QSAR) and Quantitative Structure Properties Relationship (QSPR) equations for mixed surfactants indicate the given blends of surfactant act as polar narcotic. As mentioned before, surfactants are used in personal hygiene products, laundry and dishwashing detergents which are discharged into domestic wastewater after use and thus enter the aquatic environment. Because of the increasing use of surfactants, the identification of Nano compounds with low toxicity and good surface activity properties are of great interest. Also, development Quantitative Structure Activity Relationship (QSAR) and Quantitative Structure Properties Relationship (QSPR) models provide a possible tool for this research. Quantitative Structure Activity Relationships (QSARs) relate biological, physiochemical, biochemical, pharmaceutical, clinical, medical and medicinal data such as molecular weight and solubility to biological responses. In addition, the biological, physiochemical, biochemical, pharmaceutical, clinical, medical and medicinal data describe properties such as toxicity, pharmacological effects and carcinogenicity. Using this technique only a relatively small number of experiments will be needed to construct a model which will give indications about Nano compounds that are expected to be harmful without any further biological, physiochemical, biochemical, pharmaceutical, clinical, medical and medicinal testing. Quantitative Structure Activity Relationship (QSAR) and Quantitative Structure Properties Relationship (QSPR) studies are indubitably of great importance in modern pharmaceutical, medical and medicinal chemistry and also biochemistry. 

To obtain a significant correlation, it is essential that appropriate descriptors are employed, whether they are theoretical, computational, numerical, mathematical, physical and empirical or derived from readily available experimental characteristics of molecular and chemical structures. Many descriptors reflect simple molecular and chemical properties and can thus provide insight into the biological, physiochemical, biochemical, pharmaceutical, clinical, medical and medicinal nature of the activity/property under synchrotron radiations consideration. Furthermore, using combinations of topological, physiochemical, biological, biochemical, pharmaceutical, clinical, medical and medicinal parameters along with the indicator parameters, a tremendous improvement in the statistics has been observed. Activity constants can be a key parameter for understanding and quantifying chemical and physical phenomena such as reaction rates, biological uptake, biological transport and environmental fate. 

It has been shown that acid–base properties affect the toxicity. The research for quantitative relations between the chemical and molecular structure i.e., biological, physiochemical, biochemical, pharmaceutical, clinical, medical, medicinal, structural, molecular and conformational properties and the biological, physiochemical, biochemical, pharmaceutical, clinical, medical, medicinal, structural, molecular and conformational responses is the subject of Quantitative Structure Activity Relationship (QSAR) and Quantitative Structure Properties Relationship (QSPR) studies. These relationships will hopefully help to understand and explain the driving forces behind the Nano drugs action; ultimately supporting the development of new Nano compounds exhibiting describes biological, physiochemical, biochemical, pharmaceutical, clinical, medical, medicinal, structural, molecular and conformational properties. 

In modern pharmaceutical, medical and medicinal chemistry, computer – aided Nano drugs design method such as QuantitativeStructure Activity Relationship (QSAR) and Quantitative Structure Properties Relationship (QSPR) studies have greatly accelerated the pace of Nano drugs discovery in recent decade. The underlying assumption behind Quantitative Structure Activity Relationship (QSAR) and Quantitative Structure Properties Relationship (QSPR) analysis is that the variation of biologic activity within a group of Nano compounds can be correlated with the variation of their respective structural, molecular and chemical feature. It should be noted that many machine – learning methods have been extensively applied to the process of Nano drugs discovery for building Quantitative Structure Activity Relationship (QSAR) and Quantitative Structure Properties Relationship (QSPR) models.

/pdf/cancer-risk-prediction-and-assessment-in-human-cells-under-3ro6fucjkh.pdf

Cancer Risk Prediction and Assessment in Human Cells under Synchrotron Radiations Using Quantitative Structure Activity Relationship (QSAR) and Quantitative Structure Properties Relationship (QSPR) Studies

https://hal.archives-ouvertes.fr/hal-01872907/document

Microbial degradation of aflatoxin B1: Current status and future advances.

https://research.vu.nl/ws/files/119076355/Challenges_and_perspectives_in_continuous_glucose_monitoring.pdf

Challenges and perspectives in continuous glucose monitoring

BACKGROUND
Aflatoxicol (AFL) is one of most the important metabolites of aflatoxin B1 (AFB1). AFL can be formed through enzymatic or synthetic reduction of AFB1. Various experimental and theoretical studies have been focused on the AFB1 due to its high toxicity and carcinogenicity.

RESULTS
The selective reduction of AFB1 carbonyls, molecular structure of AFL and its effect on toxicity has been studied here by the density functional theory (DFT) method. Although the toxicity of AFL is 18 times lower than that of AFB1, it has been concluded that both molecular structures have similar potency to form an exo-epoxide (AFEP) analogue which can bind to DNA.

CONCLUSION
Calculations revealed that only one of the three possible tautomers of AFL is stable, both in the gas phase and water. The electronic properties of aflatoxicol are calculated as similar to aflatoxin B1 and this may be an explanation of similar carcinogenicity and toxicity of these compounds, which has been proved by experimental results. © 2014 Society of Chemical Industry

Reduction of aflatoxin B1 to aflatoxicol: A comprehensive DFT study provides clues to its toxicity†

Diaminopyrimidine derivatives are frequently used as inhibitors of human dihydrofolate reductase, for example in treatment of patients whose immune system is affected by human immunodeficiency virus. Forty-seven dicyclic and tricyclic potential inhibitors of human dihydrofolate reductase were analyzed using the quantitative structure-activity analysis supported by DFT-based and DRAGON-based descriptors. The developed model yielded an RMSE deviation of 1.1 a correlation coefficient of 0.81. The prediction set was characterized by R2 = 0.60 and RMSE = 3.59. Factors responsible for inhibition process were identified and discussed. The resulting model was validated via cross validation and Y-scrambling procedure. From the best model, we found several mass-related descriptors and Sanderson electronegativity-related descriptors that have the best correlations with the investigated inhibitory concentration. These descriptors reflect results from QSAR studies based on characteristics of human dihydrofolate reductase inhibitors.

/pdf/a-dft-based-qsar-study-on-inhibition-of-human-dihydrofolate-1dwse1bz30.pdf

A DFT-based QSAR study on inhibition of human dihydrofolate reductase

Glucopyranose is the most stable form of glucose in solution. Identification of molecular structure of glucopyranose is very important because of its biological and synthetic significance; it is not an easy task because of the large number of possible configurations. Relative energies of exocyclic hydroxymethyl rotamers and α-β anomers of D-glucopyranose have been determined at the reference MP2/6-31G(d,p) level geometry by ab initio calculations at the infinite basis set limit of MP2 approach and with inclusion of CCSD(T) correction term evaluated with the aug-cc-pVDZ basis set in vacuum, water, dimethylsulfoxide, tetrahydrofurane and ethanol. The infinite basis set limit of MP2 level was determined by two point extrapolation using aug-cc-pVTZ and aug-cc-pVQZ basis sets. Solvent effects, relative energies and binding energies have been considered applying explicit calculations and implicit solvent models.

Anomeric and rotameric preferences of glucopyranose in vacuo, water and organic solvents.

The complex of 2,6-diacetylpyridinedihydrazone (L) with lead(II) and azide has been characterized by elemental analyses, FTIR, and single-crystal X-ray analysis. The Pb(C9H13N11) (1) crystallized in the monoclinic space group C2/c. The coordination of 1 exhibits a gap around the lead(II), possibly occupied by a stereochemically active electron lone pair on lead(II) resulting in a hemidirected complex. Antimicrobial activity of the complex is higher than the free ligand.

Supramolecular lead(II) azide complex of 2,6-diacetylpyridine dihydrazone: synthesis, molecular structure, and biological activity

The cobalt(IV) complex of 2,6-diacetylpyridine dioxime (dapdoH2) was prepared and characterized by X-ray diffraction, elemental analysis and FT-IR. The titled complex was found to crystallize in the orthorhombic space group and was screened for antibacterial and antifungal activities by the disc diffusion and microtitter plate techniques using DMF as solvent. It has been found that the antimicrobial activity of the complex [Co(dapdo)2] is slightly higher than the free ligand (dapdoH2).

Sedat Karabulut

Papers

Reduction of aflatoxin B1 to aflatoxicol: A comprehensive DFT study provides clues to its toxicity†

A DFT-based QSAR study on inhibition of human dihydrofolate reductase

Anomeric and rotameric preferences of glucopyranose in vacuo, water and organic solvents.

Supramolecular lead(II) azide complex of 2,6-diacetylpyridine dihydrazone: synthesis, molecular structure, and biological activity

Synthesis, characterization, crystal structure and biological activity of the cobalt(IV) complex of 2,6-diacetylpyridine dioxime: [Co(dapdo) 2 ]