Identification of Flavonoids as Putative ROS-1 Kinase Inhibitors Using Pharmacophore Modeling for NSCLC Therapeutics

Non-small cell lung cancer (NSCLC) is a lethal non-immunogenic malignancy and proto-oncogene ROS-1 tyrosine kinase is one of its clinically relevant oncogenic markers. The ROS-1 inhibitor, crizotinib, demonstrated resistance due to the Gly2032Arg mutation. To curtail this resistance, researchers developed lorlatinib against the mutated kinase. In the present study, a receptor-ligand pharmacophore model exploiting the key features of lorlatinib binding with ROS-1 was exploited to identify inhibitors against the wild-type (WT) and the mutant (MT) kinase domain. The developed model was utilized to virtually screen the TimTec flavonoids database and the retrieved drug-like hits were subjected for docking with the WT and MT ROS-1 kinase. A total of 10 flavonoids displayed higher docking scores than lorlatinib. Subsequent molecular dynamics simulations of the acquired flavonoids with WT and MT ROS-1 revealed no steric clashes with the Arg2032 (MT ROS-1). The binding free energy calculations computed via molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) demonstrated one flavonoid (Hit) with better energy than lorlatinib in binding with WT and MT ROS-1. The Hit compound was observed to bind in the ROS-1 selectivity pocket comprised of residues from the β-3 sheet and DFG-motif. The identified Hit from this investigation could act as a potent WT and MT ROS-1 inhibitor.     

Biomedical and Antioxidant Potentialities in Chilli: Perspectives and Way Forward

Worldwide, since ages and nowadays, traditional medicine is well known, owing to its biodiversity, which immensely contributed to the advancement and development of complementary and alternative medicines. There is a wide range of spices, herbs, and trees known for their medicinal uses. Chilli peppers, a vegetable cum spice crop, are bestowed with natural bioactive compounds, flavonoids, capsaicinoids, phytochemicals, phytonutrients, and pharmacologically active compounds with potential health benefits. Such compounds manifest their functionality over solo-treatment by operating in synergy and consortium. Co-action of these compounds and nutrients make them potentially effective against coagulation, obesity, diabetes, inflammation, dreadful diseases, such as cancer, and microbial diseases, alongside having good anti-oxidants with scavenging ability to free radicals and oxygen. In recent times, capsaicinoids especially capsaicin can ameliorate important viral diseases, such as SARS-CoV-2. In addition, capsaicin provides an ability to chilli peppers to ramify as topical agents in pain-relief and also benefitting man as a potential effective anesthetic agent. Such phytochemicals involved not only make them useful and a much economical substitute to wonder/artificial drugs but can be exploited as obscene drugs for the production of novel stuffs. The responsibility of the TRPV1 receptor in association with capsaicin in mitigating chronic diseases has also been justified in this study. Nonetheless, medicinal studies pertaining to consumption of chilli peppers are limited and demand confirmation of the findings from animal studies. In this artifact, an effort has been made to address in an accessible format the nutritional and biomedical perspectives of chilli pepper, which could precisely upgrade and enrich our pharmaceutical industries towards human well-being.     

Photoelectric effects in chlorophyll membranes

Photoinduced potentials and currents and photo-electroosmotic velocities were measured across cellulose acetate membranes impregnated with chlorophyll pigments. Chlorophyll was extracted by both solvent extraction, Chl^s, and column chromatography, Chl. Photoelectric effects in membranes prepared with the following pigments were investigated: (i) Chl^s-a + β-carotene, (ii) Chl^s-b + xanthophyll, (iii) Chl^s-a, (iv) Chl^s-b, (v) β-carotene, (vi) xanthophyll, (vii) Chl^s-a + anthraquinone, (viii) Chl^s-b + anthraquinone, (ix) Chl-a, (x) Chl-b, (xi) Chl-a + anthraquinone, (xii) Chl-b + anthraquinone, (xiii) Chl-a + benzoquinone, and (xiv) Chl-b + benzoquinone. β-Carotene, xanthophyll, Chl-a and Chl-b obrained by chromatographic separation do not show a photoinduced potential or current. However, these effects are observed when “pure” (doubly chromatographed) Chl-a or Chl-b are mixed with anthraquinone or benzoquinone. These effects are observed in systems (i), (ii), (iii), (iv), (vii) and (viii) involving Ch^s. Although photoinduced potentials and photoinduced currents are not observed in Chl-a or Chl-b membranes, photoelectroosmosis is still observed. p]Both photoinduced potentials and currents are found to depend on pH. When the pH is changed appropriately, Chl^s-a acts as photocathode while Chl^s-b becomes a photoanode. Photocurrents are considerably enhanced when the pH is lowered. The change of photopotential with temperature is found to be insignificant. Photoelectroosmosis is always found to be directed towards the dark side, regardless of the polarity of the electrodes. A model based on the role of plastiquinone has been proposed to explain these phenomena, which have excellent reproducibility. The model predicts that ΔpH = (pH)_d — (PH)₁ (where (pH)_d and (pH)₁ denote the pH on the dark and illuminated side of the membrane respectively) would be positive when the pH of the bathing solution is higher than approximately 7, while it would be negative for lower pH. This behaviour is observed in the case of mixture of pure Chl-a + anthraquinone and pure Chl-b + benzoquinone. The model also predicts photoelectroosmosis irrespective of the presence of plastiquinone, in agreement with experimental observation.     

Analytical Application of Deapg as Gravimetric Reagent II,Estimation of Pt(IV)

p-Diethylaminoanil of phenylglyoxal (abbreviated as DEAPG) precipitates Platinum (IV) quantitatively and gives greyish brown complex in the pH range 5.4 to 5.8 by adding slightly more than theoretical quantity of the ligand. It can be used for the gravimetric estimation of Pt(IV) either alone or in the presence of foreign ions.     

W-Spaces and Pseudo-differential Operators

In this article we improve the characterisation of [R.S. Pathak and S.K. Upadhyay (1994). W p -space and Fourier transformation. Proc. Amer. Math Soc ., 121 (3), 733-738.] and study the properties of pseudo-differential operator on the space , where z 1 , M 1 are convex functions and a, b are positive constants.     

Some relations between vector variational inequality problems and nonsmooth vector optimization problems using quasi efficiency

This paper deals with the relations between vector variational inequality problems and nonsmooth vector optimization problems using the concept of quasi efficiency. We identify the vector critical points, the weak quasi efficient points and the solutions of the weak vector variational inequality problems under generalized approximate convexity assumptions. To the best of our knowledge such results have not been established till now.     

Quench dynamics of edge states in 2-D topological insulator ribbons

We study the dynamics of edge states of the two dimensional BHZ Hamiltonian in a ribbon geometry following a sudden quench to the quantum critical point separating the topological insulator phase from the trivial insulator phase. The effective edge state Hamiltonian is a collection of decoupled qubit-like two-level systems which get coupled to bulk states following the quench. We notice a pronounced collapse and revival of the Lochschmidt echo for low-energy edge states illustrating the oscillation of the state between the two edges. We also observe a similar collapse and revival in the spin Hall current carried by these edge states, leading to a persistence of its time-averaged value.