Divergent synthesis and elaboration of structure activity relationship for quinoline derivatives as highly selective NTPDase inhibitor.

Quinoline derivatives have interesting biological profile. In continuation for the comprehensive evaluations of substituted quinoline derivatives against human nucleoside triphosphate diphosphohydrolases (h-NTPDases) a series of substituted quinoline derivatives (2a-g, 3a-f, 4, 5a-c, 6) was synthesized. The inhibitory activities of the synthesized compounds were evaluated against four isoenzymes of human nucleoside triphosphate diphosphohydrolases (h-NTPDases). These quinoline derivatives had IC50 (µM) values in the range of 0.20-1.75, 0.77-2.20, 0.36-5.50 and 0.90-1.82 for NTPDase1, NTPDase2, NTPDase3 and NTPDase8, respectively. The derivative 3f was the most active compound against NTPDase1 (IC50, 0.20 ± 0.02 µM) that also possessed selectivity towards NTPDase1. Similarly, derivative 3b (IC50, 0.77 ± 0.06), 2h (IC50, 0.36 ± 0.01) and 2c (IC50, 0.90 ± 0.08) displayed excellent activity corresponding to NTPDase2, NTPDase3 and NTPdase8. The compound 5c emerged as a selective inhibitor of NTPDase8. The most active compounds were then investigated to determine their mode of inhibition and finally binding interactions of the active compounds were analyzed through molecular docking studies. The obtained results strongly support the quinoline scaffold's potential as potent and selective NTPDase inhibitor.

Unilateral Vocal Cord Paralysis in a Patient With Acute Viral Hepatitis.

Hepatitis A virus is a leading cause of acute infectious hepatitis worldwide. The infection is characterized by a self-limiting course, and rarely has there been any occurrence of chronic sequelae or extra-hepatic manifestations. We report a case of unilateral vocal cord paralysis in a patient with acute hepatitis A.

Enhancing catalytic potential of gold nanoparticles by linear and cross-linked polyurethane blending.

This work describes the synthesis of gold nanoparticles (AuNPs) and their subsequent stabilization using a water-borne polyurethane matrix of micro-particles (Au/PU) by a heating method. Composites were prepared both from linear and cross-linked polyurethane (LPU and CPU). Catalytic activities of synthesized composites exhibiting 226.4 nm size were evaluated for reduction of Congo red dye. More than 90% Congo red degradation was achieved in just 6 minutes with Au/LPU. Under similar conditions, 30% of dye was degraded with Au/CPU composite in 5 minutes. The effects of different variables such as concentration of dye, catalyst dose and concentration of reagents have been optimized. The degradation process followed first order kinetics. The most efficient composite (Au/LPU) was characterized using UV/Vis, FTIR, SEM, XRD and DLS techniques. The excellent catalytic activity can be attributed to the polyurethane matrix making the dye available to catalytic sites (AuNPs).

Strain-Release-Driven Homologation of Boronic Esters: Application to the Modular Synthesis of Azetidines.

Azetidines are important motifs in medicinal chemistry, but there are a limited number of methods for their synthesis. Herein, we present a new method for their modular construction by exploiting the high ring strain associated with azabicyclo[1.1.0]butane. Generation of azabicyclo[1.1.0]butyl lithium followed by its trapping with a boronic ester gives an intermediate boronate complex which, upon N-protonation with acetic acid, undergoes 1,2-migration with cleavage of the central C-N bond to relieve ring strain. The methodology is applicable to primary, secondary, tertiary, aryl, and alkenyl boronic esters and occurs with complete stereospecificity. The homologated azetidinyl boronic esters can be further functionalized through reaction of the N-H azetidine, and through transformation of the boronic ester. The methodology was applied to a short, stereoselective synthesis of the azetidine-containing pharmaceutical, cobimetinib.

Investigation of new quinoline derivatives as promising inhibitors of NTPDases: Synthesis, SAR analysis and molecular docking studies.

Nucleoside triphosphate diphosphohydrolases (NTPDases), an important class of ectonucleotidases, are responsible for the sequential hydrolysis of extracellular nucleotides. However, over-expression of NTPDases has been linked with various pathological diseases e.g. cancer. Thus, to treat these diseases, the inhibitors of this class of enzyme are of interest. The significance of this class of enzyme encouraged us to synthesize a new class of quinoline derivatives with the aim to find selective and potent inhibitors of NTPDases. Therefore, a mild and efficient synthetic route was established for the synthesis of quinoline derivatives. The reaction was catalyzed by molecular iodine to afford the substituted quinoline derivatives. All the synthetic derivatives (3a-3w) were evaluated for their potential to inhibit the h-NTPDase1, 2, 3 and 8. Most of the compounds were identified as dual inhibitors of h-NTPDase1 and 8 with lower effects on h-NTPDase2 and 3. Two compounds i.e.3f and 3t were identified as selective inhibitor of h-NTPDase1 whereas the compound 3s inhibited the h-NTPDase8 selectively. Moreover, the compounds 3p (IC50 = 0.23 ±â€¯0.01 µM), 3j (IC50 = 21.0 ±â€¯0.03 µM) 3d (IC50 = 5.38 ±â€¯0.21 µM) and 3c (IC50 = 1.13 ±â€¯0.04 µM) were found to be the most potent inhibitors of h-NTPDase1, 2, 3 and 8, respectively. To determine the binding interaction, molecular docking studies were also carried out.