Design and pharmacophoric identification of flavonoid scaffold-based aromatase inhibitors

Aromatase is a crucial enzyme for the catalysis of aromatization reaction at the last and rate-limiting step involved in the conversion of androgenic substrates to an estrogenic substrate. A hormone-dependent breast cancer in postmenopausal woman can be cured by inhibition of estrogen biosynthesis by the help of aromatase inhibitors (AIs). The mode of interactions of flavonones with the active site of aromatase has been studied in search of potent and selective AIs as a substitute of the natural steroidal ligand. Structure-based computational approach namely, molecular docking simulations were performed to investigate the structural features of the docked complex of aromatase and flavonoid ligands. A nonsteroidal flavonoid pharmacophore showing electrostatic and steric features for selective binding within the main pocket of the catalytic active site of aromatase has been identified as an outcome of the study. The binding affinity of quercetin and isoflavone were predicted within aromatase. Isoflavone was used as a negative control to compare its binding affinities with the selected dataset. The predicted binding affinity of negative control isoflavone was in accordance with its in vitro AI efficacy. Isoflavone showed poor binding affinity and ranked last in terms of MolDock score (−86.309 kcal/molÅ) compared to dataset molecules. The generated pharmacophoric information will be helpful for the synthetic chemist to design and synthesize selective AIs with comparable binding affinity to the natural steroidal ligand.     

Positive-, negative-, and orthogonal-phase-velocity propagation of electromagnetic plane waves in a simply moving medium

Planewave propagation in a simply moving, dielectric-magnetic medium that is isotropic in the co-moving reference frame, is classified into three different categories: positive-, negative-, and orthogonal-phase-velocity (PPV, NPV, and OPV). Calculations from the perspective of an observer located in a non-co-moving reference frame show that, whether the nature of planewave propagation is PPV or NPV (or OPV in the case of non-dissipative mediums) depends strongly upon the magnitude and direction of that observer's velocity relative to the medium. PPV propagation is characterized by a positive real wavenumber, NPV propagation by a negative real wavenumber. OPV propagation only occurs for non-dissipative mediums, but weakly dissipative mediums can support nearly OPV propagation.     

Boundary-value problems and the validity of the Post constraint in modern electromagnetism

When a (frequency-domain) boundary-value problem involving a homogeneous linear material is solved to assess the validity of the Post constraint, a conflict arises between the fundamental differential equations of electromagnetism in the chosen material and a naïve application of the usual boundary conditions. It is shown here that the conflict vanishes when the boundary conditions are properly derived from the fundamental equations, and the validity of the Post constraint in modern macroscopic electromagnetism is thereby reaffirmed.     

Isotropic Maxwell-Garnett model for biisotropic-in-biisotropic mixtures

The Rayleigh scattering response of an electrically small biisotropic sphere immersed in an ambient biisotropic medium has been utilized in constructing a Maxwell-Garnett model of a composite material formed by randomly dispersing biisotropic spheres in a biisotropic host medium. It is anticipated that this work will be of interest for estimating the electromagnetic properties of particulate media.