Elucidating the aryl hydrocarbon receptor antagonism from a chemical-structural perspective

ABSTRACT

The aryl hydrocarbon receptor (AhR) plays an important role in several biological processes such as reproduction, immunity and homoeostasis. However, little is known on the chemical-structural and physicochemical features that influence the activity of AhR antagonistic modulators. In the present report, in vitro AhR antagonistic activity evaluations, based on a chemical-activated luciferase gene expression (AhR-CALUX) bioassay, and an extensive literature review were performed with the aim of constructing a structurally diverse database of contaminants and potentially toxic chemicals. Subsequently, QSAR models based on Linear Discriminant Analysis and Logistic Regression, as well as two toxicophoric hypotheses were proposed to model the AhR antagonistic activity of the built dataset. The QSAR models were rigorously validated yielding satisfactory performance for all classification parameters. Likewise, the toxicophoric hypotheses were validated using a diverse set of 350 decoys, demonstrating adequate robustness and predictive power. Chemical interpretations of both the QSAR and toxicophoric models suggested that hydrophobic constraints, the presence of aromatic rings and electron-acceptor moieties are critical for the AhR antagonism. Therefore, it is hoped that the deductions obtained in the present study will contribute to elucidate further on the structural and physicochemical factors influencing the AhR antagonistic activity of chemical compounds.     

Quinolone and isoquinolone alkaloids: the structural-electronic effects and the antioxidant mechanisms

Structural Chemistry - Quinolone and isoquinolone alkaloids, which were found in the plant kingdom, are now potential antioxidants. In this case study, a quantum calculated procedure utilizing the...     

Ferro- and antiferromagnetism in oxychalcogenides LnCrOX2 (Ln = La or Nd and X = S or Se)

The two isomorphous compounds LaCrOS₂ and LaCrOSe₂ are ferromagnetic (T_c = 35 and 51 K, respectively). This implies ferromagnetic super-superexchange interactions. NdCrOS₂ is antiferromagnetic (T_N = 72 K) and undergoes a spin-flop transition (H_c = 54 KOe at 20 K). The study of the thermal variation of Cr³⁺ and Nd³⁺ magnetic moments below T_N allows a rough estimate of the Cr---Nd and Cr---Cr exchange fields ratio (0.1).     

Study of a circuit-breaker arc with self-generated flow. I. Energytransfer in the high-current phase

This study deals with the first phase of operation, corresponding to the energy transfer between arc and gas and to the pressure rise. The experimental study is devoted to measurements of current, arc voltage, and pressure variations in N₂ and SF₆. For currents of the order of 10 kA the mean measured electric field was about 32 V/cm in SF₆ and 36 V/cm in N₂. Through a bibliographical study and a modeling approach of the interruption arc, an analysis of the role of the different mechanisms of energy transfer between the arc and SF₆ was conducted. With a 10 kA pulse, about 80% of the transfer is found to be due to convection and the rest to radiation from the arc. This transfer results in an overpressure of nearly 1 bar in SF₆ and 2 bar in N₂. It appears that the operation of this type of circuit breaker is limited to high currents: for currents below 7 kA the overpressure is lower than 0.5 bar, which does not provide efficient blowing at current zero