Remarkable regioselective position-10 bromination of bacteriopyropheophorbide-a and ring-B reduced pyropheophorbide-a

Both bacteriopyropheophorbide-a and ring-B reduced pyropheophorbide-a on reacting with NBS (N-bromosuccinamide) undergo electrophilic bromination to provide 10-bromo analogs. The electronic nature of the substituents present at position-3 did not make any difference in the regioselective outcome of the brominated products. These relatively stable brominated chlorins and bacteriochlorins provide an easy way of introducing a wide variety of functionalities, which could be extremely useful in developing improved agents for biomedical applications and supramolecular chemistry.     

Phytochemical Investigation of Artemisia pallens

Two new eudesmanolides, pallensin ( 1 ) and 4‐epipallensin ( 2 ), along with a known eudesmanolide, santonin, and a known flavone, 4‐epivalgarin, have been isolated from the aerial part of A. pallens. Their structures were established by detailed spectral studies (1D and 2D) and by comparison of their spectroscopic data with those of known compounds.     

Synthesis of α-S-galactosylceramides with a truncated sphingoid chain

We present here a convenient synthesis of the truncated sphingoid iodide 15 from d-galactose, in which Mitsunobu reaction was utilized to retrieve successfully an unwanted intermediate, thereby increasing greatly the synthetic efficiency. Subsequent reaction of 15 with the pre-prepared α-galactosyl thiol 16 led smoothly to the desired thioglycoside 17 in good yield, from which the catabolically stable thioglycoside analogs of OCH 4 and 22 were synthesized.     

Structural and thermal studies of [PVA–LiAc] : TiO2 polymer nanocomposite system

Nanocomposite polymer electrolyte consisting of polyvinyl alcohol (PVA) and lithium acetate with TiO₂ filler has been synthesised by combination of solution cast technique and sol–gel process. The composite electrolyte films were characterised by different experimental techniques. The average particle size of composite electrolytes lies between 25 and 30?nm. System is essentially ionic with maximum conductivity of polymer electrolyte 90[80PVA–20LiAc]:10TiO₂ (～4.5?×?10^?6?S?cm^?1) at room temperature.     

Effect of backbone flexibility on charge transfer rates in peptide nucleic acid duplexes

Charge transfer (CT) properties are compared between peptide nucleic acid structures with an aminoethylglycine backbone (aeg-PNA) and those with a γ-methylated backbone (γ-PNA). The common aeg-PNA is an achiral molecule with a flexible structure, whereas γ-PNA is a chiral molecule with a significantly more rigid structure than aeg-PNA. Electrochemical measurements show that the CT rate constant through an aeg-PNA bridging unit is twice the CT rate constant through a γ-PNA bridging unit. Theoretical calculations of PNA electronic properties, which are based on a molecular dynamics structural ensemble, reveal that the difference in the CT rate constant results from the difference in the extent of backbone fluctuations of aeg- and γ-PNA. In particular, fluctuations of the backbone affect the local electric field that broadens the energy levels of the PNA nucleobases. The greater flexibility of the aeg-PNA gives rise to more broadening, and a more frequent appearance of high-CT rate conformations than in γ-PNA.     

Electro-responsive polyacrylamide-grafted-gum ghatti copolymer for transdermal drug delivery application

An application of polyacrylamide-grafted-gum ghatti (PAAm-g-GGH) copolymer for transdermal delivery of an anti-psychotic drug, quetiapine fumerate triggered by electric stimulus was explored. The electro-responsive PAAm-g-GGH was prepared by free radical polymerization underneath nitrogen atmosphere subsequent to alkaline hydrolysis. The PAAm-g-GGH was used as drug reservoir gel and crosslinked films of GGH and PVA as rate controlling membranes (RCM). The reservoir gels were uniform and translucent; pH of gels was 6.56–7.06, which is in the pH range of skin and drug content was from 89.57% to 94.51%. The thickness of RCMs was 163–227?μ; thickness was increased with increased glutaraldehyde concentration and all the RCMs were permeable to water vapors. When electric stimulus was absent, a small amount of drug was permeated from the formulations, while drug conveyance was enhanced in the existence of stimulus. Drug permeation was increased with increase in electric stimulus from 2 to 8?mA. Over two fold increase in flux was observed after application of electric stimulus. Under “on–off” electric stimulus, faster drug permeation was seen under ‘on’ condition and permeation was decreased when stimulus was ‘off.’ Histopathology study confirmed reversible alteration of skin structure under electric stimulus.     

QSAR,Molecular Docking,MD Simulation and MMGBSA Calculations Approaches to Recognize Concealed Pharmacophoric Features Requisite for the Optimization of ALK Tyrosine Kinase Inhibitors as Anticancer Leads

ALK tyrosine kinase ALK TK is an important target in the development of anticancer drugs. In the present work, we have performed a QSAR analysis on a dataset of 224 molecules in order to quickly predict anticancer activity on query compounds. Double cross validation assigns an upward plunge to the genetic algorithm–multi linear regression (GA-MLR) based on robust univariate and multivariate QSAR models with high statistical performance reflected in various parameters like, fitting parameters; R² = 0.69–0.87, F = 403.46–292.11, etc., internal validation parameters; Q²_LOO = 0.69–0.86, Q²_LMO = 0.69–0.86, CCC_cv = 0.82–0.93, etc., or external validation parameters Q²_F1 = 0.64–0.82, Q²_F2 = 0.63–0.82, Q²_F3 = 0.65–0.81, R²_ext = 0.65–0.83 including RMSE_tr < RMSE_cv. The present QSAR evaluation successfully identified certain distinct structural features responsible for ALK TK inhibitory potency, such as planar Nitrogen within four bonds from the Nitrogen atom, Fluorine atom within five bonds beside the non-ring Oxygen atom, lipophilic atoms within two bonds from the ring Carbon atoms. Molecular docking, MD simulation, and MMGBSA computation results are in consensus with and complementary to the QSAR evaluations. As a result, the current study assists medicinal chemists in prioritizing compounds for experimental detection of anticancer activity, as well as their optimization towards more potent ALK tyrosine kinase inhibitor.