Synthesis and biological evaluation of carbohydrate appended hydrazinocyclopentenes with potent glycation and α-glucosidase inhibition activities

Synthesis and biological evaluation of novel alkylidenecyclopentene glycohybrids via palladium and click chemistry are described. Out of the six molecules synthesized, four molecules were screened against α-glucosidase, α-amylase, and glycation reactions. The results showed that the compound 7f with a galactose appendage is a good α-glucosidase inhibitor and a potent anti-glycation agent under in vitro conditions with an IC₅₀ value of 0.075 μM and 0.022 μM, respectively. The toxicity of the compounds against normal cell lines was checked by MTT assay.     

Predicting the Impact of Deleterious Mutations in the Protein Kinase Domain of FGFR2 in the Context of Function, Structure, and Pathogenesis—a Bioinformatics Approach

Fibroblast growth factor receptor 2 (FGFR2) controls a wide range of biological functions by regulating the cellular proliferation, survival, migration and differentiation. A growing body of preclinical data demonstrated that deregulation of the FGFR signalling through genetic modification was observed in various types of cancers. However, the extent to which genetic modifications interfere with gene regulation and their involvement in cancer susceptibility remains largely unknown. In this work, we performed in silico profiling of harmful non-synonymous single nucleotide polymorphisms (SNPs) in the protein kinase domain of FGFR2. Tolerance index, position-specific independent count score, change in free energy score (ΔΔG), Eris and FoldX indicated that seven mutations were found to be deleterious and may alter the protein function and structure. Furthermore, based on physico-chemical properties, two mutations K659N and R747H were found to be most deleterious in protein kinase domain and taken for further structural analysis. Docking study showed a complete loss of binding affinity followed by interference in hydrogen bonding and surrounding residues due to K659N and R747H mutations. In order to elucidate the mechanism behind the impact of mutation that can generate a ripple effect throughout the protein structure and ultimately affect the function, in-depth molecular dynamics simulation and principal component analysis were performed. The obtained results indicate that K659N and R747H mutations have a distinct effect on the dynamic behaviour of FGFR2 protein. Our strategy may be helpful for understanding SNP effects on proteins with function and their role in human genetic diseases and for the development of novel pharmacological strategies.     

Development and Properties of Surfactant‐Free Water‐Dispersible Cu2ZnSnS4 Nanocrystals: A Material for Low‐Cost Photovoltaics

A simple, yet novel hydrothermal method has been developed to synthesize surfactant‐free Cu₂ZnSnS₄ nanocrystal ink in water. The environmentally friendly, 2–4 nm ultrafine particles are stable in water for several weeks. Detailed X‐ray diffraction (XRD) and high‐resolution transmission electron microscopy revealed the formation of single‐crystalline‐kesterite‐phase Cu₂ZnSnS₄. Elemental mapping by scanning electron microscopy/energy dispersive spectrometry corroborated the presence of all four elements in a stoichiometric ratio with minor sulfur deficiency. Finally, Raman spectroscopy ruled out the possible presence of impurities of ZnS, Cu₂SnS₃, SnS, SnS₂, Cu_2?xS, or Sn₂S₃, which often interfere with the XRD and optical spectra of Cu₂ZnSnS₄. X‐ray photoelectron spectroscopic studies of the as‐synthesized samples confirmed that the oxidation states of the four elements match those of the bulk sample. Optical absorption analyses of thin film and solution samples showed high absorption efficiency (>10⁴ cm^?1) across the visible and near‐infrared spectral regions and a band gap E_g of 1.75 eV for the as‐synthesized sample. A non‐ohmic asymmetric rectifying response was observed in the I–V measurement at room temperature. The nonlinearity was more pronounced for this p‐type semiconductor when the resistance was measured against temperature in the range 180–400 K, which was detected in the hot‐point probe measurement.     

Isolation,Purification and Characterisation of an Organic Solvent-Tolerant Ca2+-Dependent Protease from Bacillus megaterium AU02

A new organic solvent-tolerant strain Bacillus megaterium AU02 which secretes an organic solvent-tolerant protease was isolated from milk industry waste. Statistical methods were employed to achieve optimum protease production of 43.6 U/ml in shake flask cultures. The productivity of the protease was increased to 53 U/ml when cultivated under controlled conditions in a 7-L fermentor. The protease was purified to homogeneity by a three-step process with 24 % yield and specific activity of 5,375 U/mg. The molecular mass of the protease was found to be 59 kDa. The enzyme was active over a wide range of pH (6.0–9.0), with an optimum activity at pH 7.0 and temperature from 40 to 70 °C having an optimum activity at 50 °C. The thermal stability of the enzyme increased significantly in the presence of CaCl₂, and it retained 90 % activity at 50 °C for 3 h. The K _m and V _max values were determined as 0.722 mg/ml and 0.018 U/mg respectively. The metalloprotease exhibited significant stability in the presence of organic solvents with log P values more than 2.5, nonionic detergents and oxidising agent. An attempt was made to test the synthesis of aspartame precursor (Cbz-Asp-Phe-NH₂) which was catalysed by AU02 protease in the presence of 50 % DMSO. These properties of AU02 protease make it an ideal choice for enzymatic peptide synthesis in organic media.     

Isolation and Identification of α-Glucosidase and Protein Glycation Inhibitors from Stereospermum colais

Stereospermum colais (family Bignoniaceae) is a well-known pharmacologically potent medicinal plant reported in traditional systems of medicine. Phytochemical investigation of the roots of S. colais resulted in the isolation of seven compounds, and the metabolites were screened for its α-glucosidase enzyme inhibition and anti-glycation property. The compounds identified were β-sitosterol (1), 2-(4′-hydroxyphenyl) ethyl undecanoate (2), 2-(4′-hydroxyphenyl)ethyl pentadecanoate (3), 5α-ergosta-7,22-dien-3β-ol (4), ursolic acid (5), lapachol (6), and pinoresinol (7). Ursolic acid, lapachol, and pinoresinol possessed IC₅₀ values of 119.01, 130.29, and 125.62 nM, respectively, compared to standard ascorbic acid with an IC₅₀ value of 201.01 nM. The other compounds failed to show the activity. Results of the current study showcased the possible exploration of this medicinal plant for the treatment of type 2 diabetes in line with the development of phytopharmaceutical industry.     

Synthesis of novel zerumbone derivatives via regioselective palladium catalyzed decarboxylative coupling reaction: a new class of α-glucosidase inhibitors

A new strategy for the synthesis of novel zerumbone derivatives via a regioselective palladium catalyzed decarboxylative coupling reaction using arene carboxylic acids is described. The current methodology involves the repositioning of endocyclic double bond to exocyclic double bond of zerumbone. Preliminary in vitro analysis revealed that most of the newly synthesized derivatives are potent α-glucosidase enzyme inhibitors.     

TDCR measurements of 3H, 63Ni and 55Fe using Hidex 300SL LSC device

The commercial Hidex LSC system has been used to measure triple to double coincidence ratio (TDCR), experimental counting efficiency (CE) and the absolute activity for radioactive standards of pure beta emitters viz. ³H, ⁶³Ni and ⁵⁵Fe, an electron capture nuclide. Colour and chemical quench measurements of ⁶³Ni and ⁵⁵Fe have been done. An excellent match between TDCR and CE has been obtained for beta emitters, while very large deviations have been observed for ⁵⁵Fe. The deviation between TDCR and experimental efficiency has been found to be nearly uniform. Based on this, an empirical correction factor for TDCR which gives the correct efficiency has been evaluated, to enable efficient application of this commercial instrument for ⁵⁵Fe estimation. These TDCR correction factors were further validated by applying for ⁵⁵Fe activity measurements in ASTM standard steel samples irradiated to a fixed neutron flux in research reactor CIRUS. Finally, ⁵⁵Fe activity in steel sample from APSARA reactor decommissioning waste was successfully estimated using this modified TDCR.     

Efficient Ce(III)-Catalyzed cis-Selective Synthetic Approach to γ-Lactones in Aqueous Media

The first CeCl₃ · 7H₂O-catalyzed, one-pot synthesis of α-mercapto-γ-lactones via regioselective epoxide ring opening and mercaptoacetylative cyclization cascades in water is reported. The reaction between 2-methyl-2-phenyl-1,3-oxathiolan-5-one and a variety of terminal epoxides was carried out in aqueous media to afford γ-lactones in good to excellent yields (83–94%) with complete cis diastereoselectivity. Acetophenone obtained as a by-product was also recovered and recycled easily for further use.     

Template-directed approach to solid-phase combinatorial synthesis of furan-based libraries

A novel furan based scaffold 5-hydroxymethylfurfural has been identified for the generation of combinatorial libraries using template directed approach on solid phase. This scaffold has been utilized to afford furan-based bi-heterocyclic structures with extensive chemical diversity using cycloaddition, multicomponent and cyclization reactions.