Molecular docking,PKPD, and assessment of toxicity of few chalcone analogues as EGFR inhibitor in search of anticancer agents

In the present work, molecular docking of the chalcone analogues with receptor EGFR carried out using erlotinib as reference drug is reported. About 15 chalcone analogues were analyzed CHL(1–15). Molecules CHL2, CHL3, CHL9, CHL11, and CHL15 found strong affinity for receptor EGFR exhibiting binding energies ??7.7 kcal/mol, ??7.5 kcal/mol, ??7.6 kcal/mol, ??7.9 kcal/mol, and ??8.1 kcal/mol, respectively, when erlotinib a reference drug exhibits binding energy ??7.6 kcal/mol. Toxicity for molecules was assessed against the cytochromes P450 (CYP) and P-gp using Swiss ADMET. Molecule CHL9 could be a suitable lead compound inhibitor to CYP1A2 followed by CHL2 inhibitor of CYP1A2 and CYP2C9 and CHL15 with a most stable binding affinity of ??8.1 kcal/mol, inhibiting CYP1A2, CYP2C19, and CYP2D6. CHL3 has a binding affinity of ??7.5 kcal/mol, inhibiting all the 05 CYP enzymes (CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4). CHL11 has a binding affinity of ??7.9 kcal/mol, inhibiting CYP1A2, CYP2C19, and CYP2C9. Considering inhibition of CYP family enzymes by molecules, further here we have perform the enrichment analysis to these CYP family enzymes and reported the metabolic pathways which were probably affected by inhibition of these enzymes using EnrichR online enrichment analysis server. The current predictions over these 15 chalcone derivatives will be needed to further investigate in vivo and in vitro conditions to identify the optimum therapeutic efficacy and least toxicity.

     

The Elusive Ketene (H2CCO) Channel in the Infrared Multiphoton Dissociation of Solid 1,3,5-Trinitro-1,3,5-Triazinane (RDX)

Understanding of the fundamental mechanisms involved in the decomposition of 1,3,5-trinitro-1,3,5-triazinane (RDX) still represents a major challenge for the energetic materials and physical (organic) chemistry communities mainly because multiple competing dissociation channels are likely involved and previous detection methods of the products are not isomer selective. In this study we exploited a microsecond pulsed infrared laser to decompose thin RDX films at 5 K under mild conditions to limit the fragmentation channels. The subliming decomposition products during the temperature programed desorption phase are detected using isomer selective single photoionization time-of-flight mass spectrometry (PI-ReTOF-MS). This technique enables us to assign a product signal at m/z=42 to ketene (H₂CCO), but not to diazomethane (H₂CNN; 42 amu) as speculated previously. Electronic structure calculations support our experimental observations and unravel the decomposition mechanisms of RDX leading eventually to the elusive ketene (H₂CCO) via an exotic, four-membered ring intermediate. This study highlights the necessity to exploit isomer-selective detection schemes to probe the true decomposition products of nitramine-based energetic materials.     

Pd(II) inhibition during hexacyanoferrate(III) oxidation of sugars: A kinetic study

An inhibition effect of PdCl₂ on the rate of oxidation of sugars by alkaline hexacyanoferrate(III) has been observed. The order of reactions in hexacyanoferrate(III) and OH⁻ is zero and unity, respectively, while that in sugars decreases from unity at higher sugar concentration. The kinetic data and spectrophotometric evidence support the formation of {Pd^II − (sugar)} and {Pd^II − sugar)₂} complexes and their resistance to react with Fe(CN)₆³⁻ © 1996 John Wiley & Sons, Inc.     

Modeling of reinitiation ability of polymer brushes grown by surface‐initiated photoiniferter‐mediated photopolymerization

A kinetic model developed to investigate surface‐initiated photoiniferter‐mediated photopolymerization (SI‐PMP) and parameterized using experimental thickness data from SI‐PMP of methyl methacrylate is used to examine chain extension by reinitiation. Specifically, the effects of light intensity, concentration of an added deactivator, tetraethylthiuram disulfide (TED), and initial photoiniferter (PI) concentration on the reinitiation ability of surface‐tethered PMMA layers is examined in detail. The simulations show that while increases in [TED] and decreases in light intensity affect overall rates of PMMA layer growth in a similar fashion, their effect on reinitiation ability of PMMA layers is significantly different: reinitiation ability increases with increasing [TED] but it is not improved by decreases in light intensity. Simulations also suggest that polymer layers synthesized in the presence of TED have a greater tendency to form surface‐tethered block copolymers upon reinitiation compared with polymer layers synthesized without TED and at lower light intensity. While both [PI] and [TED] affect the reinitiation ability, the effect of [TED] on reinitiation ability is identical at a given [TED]/[PI] ratio for all PI and TED concentrations tested. These findings obtained from the rate‐based model are instrumental in delineating strategies for creating tethered block copolymer layers or mixed brushes by SI‐PMP. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1586–1593, 2010     

Facile syntheses of 7,9-dimethoxypyrrolo[3,2,1-ij]quinolin-6-ones

The activated dimethoxypyrrolo[3,2,1-ij]quinolin-6-one ring system was synthesized via two approaches, starting from an indole and quinolin-4-one, respectively. Subsequent demethylation led to both monohydroxy- and dihydroxypyrrolo[3,2,1-ij]quinolin-6-ones.     

The Lowering of the Spectral Series Limit of Hydrogen and Carbon in a Plasma

The lowering of the ionization potentials of hydrogen and carbon atoms immersed in a high temperature and high density thermal plasma generated in a wall stabilized arc have been estimated from the advance or shift of their respective series limits in the vacuum ultraviolet region of the spectrum for different electron densities and temperatures. Results show a close agreement with those theoretical calculations in which the effects of both microfield and polarization terms are added. However, our electron densities are lower by about two orders of magnitude than the critical electron densities required by theory for the inclusion of the microfield term. The question of validity of a critical electrom density will be discussed.     

Electrochemical treatment of wastewater from a phosphoric acid manufacturing plant

Phosphoric acid plant wastewater containing fluoride, phosphate and chemical oxygen demand etc., was treated using electrooxidation and electroflocculation methods. A maximum of 82% F- and 22.7% COD were removed using Ti/Pt(5c) under electrooxidative conditions. Electrooxidation with respect to F- removal is found mass-transfer limited, and removals below 5-6 mg/L F- are not achievable. Electroflocculation using Al anode resulted in better removal of F-, COD and PO4(3-). The various results obtained are discussed in this paper.     

Stereoselective construction of cis-2,6-disubstituted tetrahydropyrans via the reductive etherification of delta-trialkylsilyloxy substituted ketones: total synthesis of (-)-centrolobine

[reaction: see text] The stereoselective intramolecular reductive etherification of delta-trialkylsilyloxy substituted ketones with catalytic bismuth tribromide and triethylsilane provides a convenient method for the construction of cis-2,6-disubstituted tetrahydropyrans. This method was highlighted in the key step of an expeditious total synthesis of the antibiotic, (-)-centrolobine.