Identification of indoline-2-thione analogs as novel potent inhibitors of α-melanocyte stimulating hormone induced melanogenesis

Based on the hits, 3,4-dihydroquinazoline-2-thione (1) and benzimidazole-2-thione (2), a series of indole-2-thione (3) and indole-2-thiol inhibitors (4) of melanogenesis were designed, synthesized and evaluated in melanoma B16 cells under the stimulant of α-melanocyte stimulating hormone (α-MSH). The indole-2-thione compounds (3a-g) exhibited an effective inhibitory activity on melanin synthesis. The Structure-Activity Relationship (SAR) studies of 2 have revealed that in potent inhibitor 3a (>100% inhibition at 30 μM, IC50=1.40 μM) the role of nitrogen (3-N) at 3-position is insignificance. In addition, the hydrophobic substituents of 3 were better than the hydrophilic one. However, conversion of thione (-C=S, 3) to thiol (-C-SH, 4) led to decrease in the potency.     

Effect of mobile phase on resolution of the isomers and homologues of tocopherols on a triacontyl stationary phase

Reversed-phase liquid chromatographic (RPLC) separation of isomers and homologues of similar polarity is challenging. Tocopherol isomers and homologues are one such example. α, β, γ, and δ-tocopherols have been successfully separated by RPLC on triacontyl (C₃₀) stationary phase. System suitability was tested by using four mobile phases, and observed chromatographic separations of β and γ-tocopherols were compared. Comparison indicated that methanol–tert-butyl methyl ether (TBME) 95:5 (v/v) at a flow rate of 0.75 mL min^?1 was the best mobile phase. Detection systems were also evaluated on the basis of limit of quantification; it was concluded that fluorescence detection was best. The method was validated by analysis of two homologues and two isomers of tocopherol in sesame, maize, and soybean samples. MS coupled with an ESI interface in negative-ion mode [M ? H]^? was used for identification of individual components. It was concluded that addition of TBME to methanol was required to enhance the separation of β and γ-tocopherols, although methanol alone provided similar results. The applicability of the method to cereal, pulse, and oilseed samples was confirmed. The reproducibility of the procedure was good, with relative standard deviations in the range 1.7–3.9 %. Recovery of tocopherols added to sesame samples ranged from 91 to 99 %.

Organocatalytic Asymmetric Mannich Cyclization of Hydroxylactams with Acetals: Total Syntheses of (−)‐Epilupinine, (−)‐Tashiromine,and (−)‐Trachelanthamidine

An asymmetric, organocatalytic, one‐pot Mannich cyclization between a hydroxylactam and acetal is described to provide fused, bicyclic alkaloids bearing a bridgehead N atom. Both aliphatic and aromatic substrates were used in this transformation to furnish chiral pyrrolizidinone, indolizidinone, and quinolizidinone derivatives in up to 89 % yield and 97 % ee. The total syntheses of (−)‐epilupinine, (−)‐tashiromine, and (−)‐trachelanthamidine also achieved to demonstrate the generality of the process.     

Synthesis,Physicochemical and Optical Characterization of Novel Fluorescing Complex: <Emphasis Type="Italic">o</Emphasis>-Phenylenediamine—Benzoin

The complex of o-phenylenediamine (o-PDA) and benzoin (BN) was synthesized adopting solid state reaction by mixing of their melt together followed by chilling. The phase diagram study shows the formation of a complex in 1:1 molar ratio with congruent melting point and two eutectics lying on either side of complex. The formation of complex was confirmed using the FTIR, NMR, mass spectroscopy, powder XRD and DSC studies. The optical properties of the parent component, their complex and few other compositions nearby the complex were studied using absorption and laser luminescence techniques. The significantly higher green/yellow emission was noted with newly synthesized complex as compared to that of their parents as well as other compositions of o- PDA and BN.     

Conformation of a terminally protected βγ hybrid dipeptide Boc‐Ant‐Gpn‐OMe stabilized by C6/C7 hydrogen bonds

The hybrid βγ dipeptide, methyl 2‐[1‐({2‐[(tert‐butoxycarbonyl)amino]benzamido}methyl)cyclohexyl]acetate (Boc‐Ant‐Gpn‐OMe), C₂₂H₃₂N₂O₅, adopts a folded conformation stabilized by intramolecular six‐ (C₆) and seven‐membered (C₇) hydrogen‐bonded rings, together with weak C—H...O and C—H...π interactions, resulting in a ribbon‐like structure.     

Folded conformations due to arene interactions in dissymmetric and symmetric butylidene‐linker models based on pyrazolo[3,4‐d]pyrimidine,purine and 7‐deazapurine

The butylidene‐linker models 1‐[2‐(2,6‐dimethylsulfanyl‐9H‐purin‐9‐yl)‐2‐methylidenepropyl]‐4,6‐bis(methylsulfanyl)‐1H‐pyrazolo[3,4‐d]pyrimidine, C₁₈H₂₀N₈S₄, (XI), 7,7′‐(2‐methylidenepropane‐1,3‐diyl)bis[3‐methyl‐2‐methylsulfanyl‐3H‐pyrrolo[2,3‐d]pyrimidin‐4(7H)‐one], C₂₀H₂₂N₆O₂S₂, (XIV), and 7‐[2‐(4,6‐dimethylsulfanyl‐1H‐pyrazolo[3,4‐d]pyrimidin‐1‐yl)‐2‐methylidenepropyl]‐3‐methyl‐2‐methylsulfanyl‐3H‐pyrrolo[2,3‐d]pyrimidin‐4(7H)‐one, C₁₉H₂₁N₇OS₃, (XV), show folded conformations in solution, as shown by ¹H NMR analysis. This folding carries over to the crystalline state. Intramolecular π–π interactions are observed in all three compounds, but only (XIV) shows additional intramolecular C—H...π interactions in the solid state. As far as can be established, this is the first report incorporating the pyrrolo[2,3‐d]pyrimidine nucleus for such a study. In addition to the π–π interactions, the crystal structures are also stabilized by other weak intermolecular C—H...S/N/O and/or S...N/S interactions.     

Optimization of synthetic parameters for Tl-2201 superconducting phase by flash sintering process

Samples with nominal composition Tl₂Ba₂Cu_1.2 (copper-rich Tl-2201) were calcined at various temperature, i.e. from 865 °C to 910°C and for various durations (10–20 h). The samples were sintered for 31/2 min at various temperatures. The X-ray powder diffraction pattern indicates that most of the Tl-Ba-Cu samples (Tl-2201) are single-phase materials. All the lines in the X-ray pattern are indexable on a tetragonal unit cell showing tetragonal symmetry having space group 14/mmm with a=3.86 Å C=23.11 ± 0.06 Å as unit cell parameters. R−T and AC susceptibility measurements show T^on_c, from 90 to 104 K. There is an elongation of the c-axis (c=23.24 Å) for the sample showing the highest T_c. Wet chemical analysis confirms the deficiency of thallium. This suggests some substitution of Cu in place of thallium which leads to an increase in the average oxidation state of copper, responsible for the creation of holes (charge carriers).