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The allosteric regulation of pyruvate kinase M2 (PKM2) affects the switching of the PKM2 protein between the high-activity and low-activity states that allow ATP and lactate production, respectively. PKM2, in its low catalytic state (dimeric form), is chiefly active in metabolically energetic cells, including cancer cells. More recently, PKM2 has emerged as an attractive target due to its role in metabolic dysfunction and other interrelated conditions. PKM2 (dimer) activity can be inhibited by modulating PKM2 dimer-tetramer dynamics using either PKM2 inhibitors that bind at the ATP binding active site of PKM2 (dimer) or PKM2 activators that bind at the allosteric site of PKM2, thus activating PKM2 from the dimer formation to the tetrameric formation. The present perspective focuses on medicinal chemistry approaches to design and discover PKM2 inhibitors and activators and further provides a scope for the future design of compounds targeting PKM2 with better efficacy and selectivity.

Recent years have seen great advances in utilizing quorum sensing (QS) and its inhibition, including application of X-ray crystallography, and genetic engineering to improve and develop an array of analytical tools for medical applications. Through utilization of X-ray crystallography to computational approaches, our understanding of QS and quorum sensing inhibition (QSIn) has grown by leaps. Bacterial circuitries are usually characterized by high specificity, selectivity and sensitivity, and thus suggest applications leading to low cost, miniaturization of circuitry for portable equipment and potential multiplexing. This review is intended to give its reader an overview of technologies based on QS and QSIn for medical use. The sections: techniques and technology platforms/protocols towards discovery and development of quorum sensing inhibitor (QSI), the advancement in technology towards theragnostic applications and technology enabled development of QS and QSIn as an anti-virulence strategy are aimed to provide current research insights. Specifically, we examine screening of pathogens using aptamers, biofilm prevention, vaccine development and treatment of infections and cancer.

Quorum sensing (QS) is a bacterial signaling phenomenon wherein bacteria regulate gene expression as per the concentration of signaling molecule. In the microbial milieu, bacteria use QS to sense their immediate environment and in-turn adjust QS genes. Our knowledge of this continuous process of biosensing and biomonitoring of QS signaling molecule and QS circuits has evolved over a period of time. Herein, we attempt to follow impact of newer bioanalysis techniques in understanding this QS phenomenon based on only recent technology platforms. Some of the technology platforms are at proof of concept stage wherein feasibility for QS studies is being demonstrated. We attempt to understand the enormous possibilities/potential these technologies withhold. Advancements in QS systems led researchers to attempt potential application of QS systems itself as technology platform. In this book chapter, few specific applications of QS system towards biosensing and biomonitoring are explored and covers above mentioned topics in four sections: (a) advanced structural based techniques involved in QS study (b) advanced biosensing and biomonitoring technologies (c) microarray technology (d) QS technologies for biosensing and biomonitoring activity. Specific examples are elaborated in details and for comprehensive reading on technology platform reader could refer to the references. In summary, advanced technology towards bioanalysis and applications of QS itself as biosensing and biomonitoring technology are discussed. The critical analysis, current trends, potential technology applications and the path forward are touched upon in key opinion and conclusion.

A novel synthetic route to substituted esters of imidazoles, oxazoles, thiazoles, and diethyl pyrazine-2,5-dicarboxylates via C-formylation of glycine ethyl ester hydrochloride is reported. This methodology is simple, robust, and gives good yields of different heterocyclic esters in one or two steps from a common acyclic precursor and is amenable to large scale synthesis.

In this paper, we investigated the intra-species bacterial quorum sensing at the single cell level using a double droplet trapping system. Escherichia coli transformed to express the quorum sensing receptor protein, LasR, were encapsulated in microdroplets that were positioned adjacent to microdroplets containing the autoinducer, N-(3-oxododecanoyl)- l-homoserine lactone (OdDHL). Functional activation of the LasR protein by diffusion of the OdDHL across the droplet interface was measured by monitoring the expression of green fluorescent protein (GFP) from a LasR-dependent promoter. A threshold concentration of OdDHL was found to induce production of quorum-sensing associated GFP by E. coli. Additionally, we demonstrated that LasR-dependent activation of GFP expression was also initiated when the adjacent droplets contained single E. coli transformed with the OdDHL synthase gene, LasI, representing a simple quorum sensing circuit between two droplets.

A microfluidic device capable of exploiting the permeability of small molecules through polydimethylsiloxane (PDMS) has been fabricated in order to control the contents of microdroplets stored in storage wells. We demonstrate that protein precipitation and crystallization can be triggered by delivery of ethanol from a reservoir channel, thus controlling the protein solubility in microdroplets. Likewise quorum sensing in bacteria was triggered by delivery of the auto-inducer N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) through the PDMS membrane of the device.

A series of highly functionalised γ-hydroxyacryl γ-hydroxybutenolides, 2, were synthesised in 25–50% overall yields in two or three steps from 2-furfural using a tandem Baylis–Hillman-singlet oxygen oxidation reaction.

The scope and limitations of a regioselective synthesis of either alpha- or beta-substituted gamma-hydroxybutenolides from 3-furfural and enones are described. The sequence features a Baylis-Hillman reaction followed by singlet oxygen oxidation with use of either an amine base or TBAF as the regioselectivity switches. Structural studies in solution on some of the resulting gamma-hydroxybutenolides are also reported.

Here we present the design, fabrication and operation of a microfluidic device to trap droplets in a large array of droplet pairs in a controlled manner with the aim of studying the transport of small molecules across the resultant surfactant bilayers formed between the droplet pairs.

A series of highly functionalised γ-hydroxyacryl γ-hydroxybutenolides, 2, were synthesised in 25–50% overall yields in two or three steps from 2-furfural using a tandem Baylis–Hillman-singlet oxygen oxidation reaction.

The scope and limitations of a regioselective synthesis of either alpha- or beta-substituted gamma-hydroxybutenolides from 3-furfural and enones are described. The sequence features a Baylis-Hillman reaction followed by singlet oxygen oxidation with use of either an amine base or TBAF as the regioselectivity switches. Structural studies in solution on some of the resulting gamma-hydroxybutenolides are also reported.

A facile synthesis of alpha-substituted gamma-hydroxybutenolides from 3-furfural was achieved using a Baylis-Hillman reaction followed by singlet oxygen oxidation. The regioselectivity of this conversion was controlled by using TBAF.

A facile synthesis of beta-functionalized gamma-hydroxybutenolides was achieved using a Baylis-Hillman reaction followed by singlet oxygen oxidation. The conversion from 3-furfural was regio- and diastereoselective. [reaction: see text].

A variety of substituted aryl amines were transformed into aryl azides using t-BuONO and moist NaN 3 in t-BuOH in good to excellent yields. Smooth transformation was observed with anilines, having electron withdrawing anddonating groups. Both acid- and base-sensitive groups survived the reaction conditions.

The title compound, C28H32N2O9Si, contains a rigid [3,3]-bicyclic oxazoledione core. The substituent on the quaternary bridge C atom contains two long-chain hydro­phobic groups that are in extended conformations.