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. Antivirulence activities were screened by analysing the effect of compounds on the production of virulence factors like pyocyanin, LasA protease, cell surface hydrophobicity, and rhamnolipid. The best ligands towards the quorum sensing proteins LasR, RhlR, and PqsR were recognised using a molecular docking study. The gene expression in P. aeruginosa after treatment with test compounds was evaluated on quorum sensing genes including rhlA, lasB, and pqsE. The antibiofilm potential of chalcones and flavonols was confirmed by the efficient reduction in the production of virulence factors and downregulation of gene expression.

A concise update on the synthetic transformation of aurones via asymmetric cycloaddition, annulation, and Michael/Mannich reactions.

This review provides a comprehensive overview of the significance of aurone cores in organic chemistry, highlighting their crucial role as synthetic intermediates. With their innate electrophilic reactivity and convenient accessibility, aurone cores play a vital role in catalysing the development of novel methodologies and facilitating the creation of intricate compounds. The objective of this review is to present a current and insightful compilation that summarizes the progress in aurone synthetic transformations, focusing on diverse cycloaddition ([3 + 2], [4 + 2], [4 + 3], [10 + 2]) and annulation reactions.

Synthesis and study of antibiofilm and antivirulence properties of flavonol analogues generated by palladium catalyzed ligand free Suzuki-Miyaura coupling against Pseudomonas aeruginosa 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. The arylated products were acquired by the coupling of a variety of aryl boronic acids with flavonols under Pd(OAc)2 catalyzed reaction conditions in a ligand-free reaction strategy. Subsequently, the antibiofilm and antivirulence properties of the arylated flavonols against Pseudomonas aeruginosa PAO1 were studied thoroughly. The best ligands for quorum sensing proteins LasR, RhlR, and PqsR were identified using molecular docking study. These best fitting ligands were then studied for their impact on gene expression level of P. aeruginosa by RT-PCR towards quorum sensing genes lasB, rhlA, and pqsE. The downregulation in the gene expression with the effect of synthesized flavonols endorse the antibiofilm efficiency of the compounds.

Advances in the site-selective C-5, C-3 and C-2 functionalization of chromones via sp2 C-H activation.

In this work, site-selective C-H activation at C-5, C-3 and C-2 positions of chromones for the introduction of structural diversity to the chromone scaffold was studied. The keto group of the chromone moiety acts as the directing group for the selective functionalization of chromones at the C-5 position. Furthermore, the C-H functionalization at the electron-rich C-3 position of the chromone can be achieved using electrophilic coupling partners. The C-H functionalization at the C-2 position can be possible using nucleophilic coupling partners. The direct functionalization methods provide a better pathway for the generation of C-5, C-3 and C-2-substituted chromones with good atom economy than that of classical pre-functionalized reaction protocols.

Chromone, A Privileged Scaffold in Drug Discovery: Developments in the Synthesis and Bioactivity.

Chromones are the class of secondary metabolites that broadly occur in the plant kingdom in a noticeable quantity. This rigid bicyclic system has been categorized "as privileged scaffolds in compounds" in medicinal chemistry. Their wide biological responses have made them an important moiety in a drug discovery program. This review provides updates on the various methods of synthesis of chromones and biological applications in medicinal chemistry. Various synthetic strategies for the construction of chromones include readily available phenols, salicylic acid and its derivatives, ynones, chalcones, enaminones, and 2-hydroxyarylalkylketones as starting materials. Synthesis of chromones by using metal, metal-free, nanomaterials and different other catalysts is herein included. Details of diverse biological activities of chromone derviatives, such as anti-cancer, antimicrobial, anti-viral, anti-inflammatory, antioxidant, as Monoamine Oxidase-B (MAO-B) inhibitors, anti- Alzheimer's agents, anti-diabetic agents, having antihistaminic potential, and acting as antiplatelet agents, are discussed.