Attenuation of Quorum Sensing Mediated Virulence Factors and Biofilm Formation in Pseudomonas Aeruginosa PAO1 by Substituted Chalcones and Flavonols.

Flavonoids epitomize structural scaffolds in many biologically active synthetic and natural compounds. They showcase a diverse spectrum of biological activities including anticancer, antidiabetic, antituberculosis, antimalarial, and antibiofilm activities. The antibiofilm activity of a series of new chalcones and flavonols against clinically significant Pseudomonas aeruginosa PAO1 strain was studied.

Synthesis and study of antibiofilm and antivirulence properties of flavonol analogues generated by palladium catalyzed ligand free Suzuki-Miyaura coupling against PAO1.

The Suzuki-Miyaura coupling is one of the ubiquitous method for the carbon-carbon bond-forming reactions in organic chemistry. Its popularity is due to its ability to undergo extensive coupling reactions to generate a broad range of biaryl motifs in a straightforward manner displaying a high level of functional group tolerance. A convenient and efficient synthetic route to arylate different substituted flavonols through the Suzuki-Miyaura cross-coupling reaction has been explained in this study.

Rational Computational Approaches in Drug Discovery: Potential Inhibitors for Allosteric Regulation of Mutant Isocitrate Dehydrogenase-1 Enzyme in Cancers.

Mutations in homodimeric isocitrate dehydrogenase (IDH) enzymes at specific arginine residues result in the abnormal activity to overproduce -2 hydroxyglutarate (-2HG), which is often projected as solid oncometabolite in cancers and other disorders. As a result, depicting the potential inhibitor for -2HG formation in mutant IDH enzymes is a challenging task in cancer research. The mutation in the cytosolic IDH1 enzyme at R132H, especially, may be associated with higher frequency of all types of cancers.

Chiral discrimination in a mutated IDH enzymatic reaction in cancer: a computational perspective.

Chiral discrimination in biological systems, such as L-amino acids in proteins and d-sugars in nucleic acids, has been proposed to depend on various mechanisms, and chiral discrimination by mutated enzymes mediating cancer cell signaling is important in current research. We have explored how mutated isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate which in turn is converted to d-2-hydroxyglutatrate (d-2HG) as a preferred product instead of l-2-hydroxyglutatrate (l-2HG) according to quantum chemical calculations. Using transition state structure modeling, we delineate the preferred product formation of d-2HG over l-2HG in an IDH active site model.