Selective Interactions of O-Methylated Flavonoid Natural Products with Human Monoamine Oxidase-A and -B

A set of structurally related O-methylated flavonoid natural products isolated from Senecio roseiflorus (1), Polygonum senegalense (2 and 3), Bhaphia macrocalyx (4), Gardenia ternifolia (5), and Psiadia punctulata (6) plant species were characterized for their interaction with human monoamine oxidases (MAO-A and -B) in vitro. Compounds 1, 2, and 5 showed selective inhibition of MAO-A, while 4 and 6 showed selective inhibition of MAO-B. Compound 3 showed ~2-fold selectivity towards inhibition of MAO-A. Binding of compounds 1–3 and 5 with MAO-A, and compounds 3 and 6 with MAO-B was reversible and not time-independent. The analysis of enzyme-inhibition kinetics suggested a reversible-competitive mechanism for inhibition of MAO-A by 1 and 3, while a partially-reversible mixed-type inhibition by 5. Similarly, enzyme inhibition-kinetics analysis with compounds 3, 4, and 6, suggested a competitive reversible inhibition of MAO-B. The molecular docking study suggested that 1 selectively interacts with the active-site of human MAO-A near N5 of FAD. The calculated binding free energies of the O-methylated flavonoids (1 and 4–6) and chalcones (2 and 3) to MAO-A matched closely with the trend in the experimental IC_50′s. Analysis of the binding free-energies suggested better interaction of 4 and 6 with MAO-B than with MAO-A. The natural O-methylated flavonoid (1) with highly potent inhibition (IC₅₀ 33 nM; Ki 37.9 nM) and >292 fold selectivity against human MAO-A (vs. MAO-B) provides a new drug lead for the treatment of neurological disorders.     

Glyoxylic acid in the reaction of isatoic anhydride with amines: a rapid synthesis of 3-(un)substituted quinazolin-4(3H)-ones leading to rutaecarpine and evodiamine

A dual reactant/catalyst role of glyoxylic acid in the reaction of isatoic anhydride with various amines afforded a novel, robust and rapid synthesis of 3-(un)substituted quinazolin-4(3H)-ones. This metal catalyst-free reaction proceeds via an unusual and unexpected cleavage of C–C bond. A shorter and common route to two alkaloids, that is, rutaecarpine and evodiamine is also accomplished.     

Crystal Engineering of Stable Temozolomide Cocrystals

The antitumor prodrug temozolomide (TMZ) decomposes in aqueous medium of pH≥7 but is relatively stable under acidic conditions. Pure TMZ is obtained as a white powder but turns pink and then brown, which is indicative of chemical degradation. Pharmaceutical cocrystals of TMZ were engineered with safe coformers such as oxalic acid, succinic acid, salicylic acid, d,l ‐malic acid, and d,l ‐tartaric acid, to stabilize the drug as a cocrystal. All cocrystals were characterized by powder X‐ray diffraction (PXRD), single crystal X‐ray diffraction, and FT‐IR as well as FT‐Raman spectroscopy. Temozolomide cocrystals with organic acids (pK_a 2–6) were found to be more stable than the reference drug under physiological conditions. The half‐life (T_1/2) of TMZ–oxalic and TMZ–salicylic acid measured by UV/Vis spectroscopy in pH 7 buffer is two times longer than that of TMZ (3.5 h and 3.6 h vs. 1.7 h); TMZ–succinic acid, TMZ–tartaric acid, and TMZ–malic acid also exhibited a longer half‐life (2.3, 2.5, and 2.8 h, respectively). Stability studies at 40 °C and 75 % relative humidity (ICH conditions) showed that hydrolytic degradation of temozolomide in the solid state started after one week, as determined by PXRD, whereas its cocrystals with succinic acid and oxalic acid were intact at 28 weeks, thus confirming the greater stability of cocrystals compared to the reference drug. The intrinsic dissolution rate (IDR) profile of TMZ–oxalic acid and TMZ–succinic acid cocrystals in buffer of pH 7 is comparable to that of temozolomide. Among the temozolomide cocrystals examined, those with succinic acid and oxalic acid exhibited both an improved stability and a comparable dissolution rate to the reference drug.     

Thermo emf studies on CdTe:Sb Thin Films

Thermal transport properties have been studied on as-grown and annealed CdTe:Sb thin films of different thicknesses and concentrations of Sb. These films were prepared by sequential vacuum deposition of CdTe and Sb on clean and hot glass substrates held at 210 °C temperature at a constant rate of deposition. From these studies all the films were found to be p-type. It is also observed that the thermoelectric power increases with Sb concentgration, thickness of the film and with annealing process. Fermi-energy variation with temperature have been calculated on the basis of thermo emf data. All these results have been explained on the basis of defects introduced by Sb doping.     

Electrical transport properties of CdTe:Sb films

Hall coefficient and dc conductivity measurements are made on p-type CdTe:Sb films grown by vacuum evaporation technique on glass substrate. The grain boundary potential barrier, which is found mainly to limit the mobility of carriers is calculated as a function of film thickness. The n-type conduction is found to dominate over p-type conduction above about 330 K. The ratio of electron to hole mobility is also calculated.     

Role of Impurity Precipitates on Microhardness of KBr:Ba2+ Crystals

Microhardness of KBr crystals doped with various concentration of Ba²⁺ have been investigated in the asgrown state and after quenching from various elevated temperatures. It is observed that hardness increases with increase in impurity concentration and at high concentration the hardness starts decreasing. Microstructural investigations have showed the formation of visible precipitates at high concentrations. The heat treatment studies showed that in crystals quenched from elevated temperatures the visible precipitates dissociate and hardness increases.     

Microhardness studies on some compound semiconductors

Vickers microhardness studies on some III–V and II–VI compound semiconductors have been made. The results showed that ZnS has the highest microhardness value. These results are compared with other properties of the crystals such as melting point, ionicity etc. Variation of microhardness with load was also studied on all the crystals. The results indicated that the hardness value increases at low loads. These results have been analysed by using resistance pressure model and interpreted.     

Dielectric and electrical studies on as-grown CeO2 films

Thin film capacitors of CeO₂ were fabricated by thermal evaporation. The dielectric properties of these films were studied in the frequency range 0.05–16 KHz at various temperatures, starting from liquid nitrogen temperature to 390 K. The effect of annealing on capacitance and tan δ were studied for different frequencies. The behaviour was explained on the basis of relief in strain energy. The plot between current density and temperature was drawn, and from the slope of the plot the activation energy was calculated and found to be 0.52 ev. The results were discussed.     

Electrical properties of Al-CeO2-Al thin film capacitor structures

Cerium Oxide films were prepared by vacuum thermal evaporation from tantalum boat in a conventional vacuum coating unit. Current-voltage characteristics were studied for different film thicknesses. The breakdown voltage (V_B) and dielectric field strength (E_B) were calculated. It is found that the breakdown voltage increases and dielectric field strength decreases as the thickness of the film increases. The applicability of Forlani-Minnaja relation is discussed. Current-voltage characteristics were also drawn at different temperatures and breakdown voltages were calculated. The breakdown voltage decreases as the temperature of the structure increases but the variation is nonlinear. The variation of current density with temperature was studied and the activation energy for the migration of charge carriers was calculated and it is about 0.52 ev. The results were discussed.     

5-(Perfluorooctylthio)acetamidofluorescein (5-FOAF) as a convenient tag for inspecting the surface coverage of fluorinated coatings

Fluorinated compounds are commonly used for anti-stick coating but it is difficult to inspect the coverage of the coating without expensive instruments. Herein, we demonstrated that the 5-(perfluorooctylthio)acetamidofluorescein (5-FOAF) probe can be synthesized in one step and used as a testing reagent to inspect the fluorinated coating on silica- or metal-based surfaces. 5-FOAF is composed of a perfluoroalkyl domain, which has high specific affinity towards fluorinated compounds, and a fluorophore domain, which exhibits fluorescence emission visible by naked eyes. Thus, 5-FOAF will retain on the surface coated with fluorinated compounds but not on the un-coated surface and the emitted fluorescence from the retained tags serves as a semi-quantitative measure of the fluorine coverage across the surface. For this study, silica-based or metal-based surfaces were activated by silane chemistry and then coated with fluorinated compounds. The coating procedure was judiciously optimized to achieve a homogeneous coating. 5-FOAF probe was synthesized in-house and shown to retain on the fluorinated surface 2-5 times stronger than the bare surface. Moreover, by studying the retention on a non-fluoro hydrophobic substrate made of polydimethylsiloxane, the affinity of 5-FOAF with the fluorinated coating was confirmed to be specific and distinguishable from nonspecific hydrophobic interaction. In conclusion, we synthesized a novel chemical, 5-FOAF, and demonstrated its usefulness as a simple testing reagent for fluorinated coatings.