LpxC inhibition: Potential and opportunities with carbohydrate scaffolds.

Uridine diphosphate-3-O-(hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is a key enzyme involved in the biosynthesis of lipid A, an essential building block, for the construction and assembly of the outer membrane (OM) of Gram-negative bacteria. The enzyme is highly conserved in almost all Gram-negative bacteria and hence has emerged as a promising target for drug discovery in the fight against multi-drug resistant Gram-negative infections. Since the first nanomolar LpxC inhibitor, L-161,240, an oxazoline-based hydroxamate, the two-decade-long ongoing search has provided valuable information regarding essential features necessary for inhibition.

Storage and Temperature Stability of Emulsified Biodiesel-Diesel Blends.

The scarcity of fossil fuel has led to the recent worldwide commercialization of biodiesel-blended diesel. The benefits associated with emulsion fuels have encouraged researchers to study the blended emulsified fuels in diesel engines. Recent results show the effectiveness of blended emulsified fuels in terms of better fuel economy and less harmful emissions.

Natural Products & Bioactivity Inspired Synthetic Pursuits Interfacing with Carbohydrates: Ongoing Journey with C-Glycosides.

Natural products, remains the most important source for the discovery of new drugs for the treatment of human diseases. This has inspired the synthetic community to design and develop mimics of natural products either to answer important questions in biology or to explore their therapeutic potentials. Glycosides present themselves abundantly in nature, right from the cell surface receptors to natural products of any origin.

Novel Chemical Scaffolds to Inhibit the Neutral Amino Acid Transporter BAT1 (SLC6A19), a Potential Target to Treat Metabolic Diseases.

Lack of BAT1 (SLC6A19) partially protects mice against the onset of non-alcoholic steatohepatitis (NASH). To achieve a similar outcome through pharmacological treatment, we improved previously identified inhibitors of BAT1 by medicinal chemistry and identified second generation inhibitors by high through-put screening. Modified diarylmethine compounds inhibited BAT1 with IC values ranging from 8-90 μM.

Discovery of an isocoumarin analogue that modulates neuronal functions via neurotrophin receptor TrkB.

Isocoumarins are lactone ring-containing natural products, are quite abundant in microbes and higher plants, and have been shown to exhibit a broad range of pharmacological properties. However, the molecular mechanism or target of this class of molecules is not known. In this study, we have synthesized 14 isocoumarin derivatives and evaluated for their activity at TrkB receptor in transiently transfected HEK293T cells.

Stereoselective total synthesis of Oxylipin from open chain gluco-configured building block.

Total synthesis of naturally occurring Oxylipin has been achieved from open chain gluco-configured building block which is readily assembled from inexpensive and commercially available D-(+)-gluconolactone. Grignard reaction and Wittig olefination reactions are key steps for the requisite CC bond formation.

Valuable building block for the synthesis of lunularic acid, hydrangeic acid and their analogues.

A new functionalised sulphone-based building block has been synthesised that enabled C-C bond formation through Julia olefination. The utility of developed building block was demonstrated by successful synthesis of two natural products lunularic acid, hydrangeic acid and initial libraries of their analogues.

Inhibition of the enzymes in the leukotriene and prostaglandin pathways in inflammation by 3-aryl isocoumarins.

The biosynthesis of leukotrienes in one of the arachidonic acid pathways and PGE in the other by 5-LOX and mPGES1 respectively, play pivotal roles in augmenting inflammatory responses. PGE is known to participate in cancer pathological processes as well. Isocoumarins are natural compounds with a wide range of biological activities.

Study of aqueous phase aggregation of FTY720 (fingolimod hydrochloride) and its effect on DMPC liposomes using fluorescent molecular probes.

This work focuses on the study of aqueous phase aggregation of the recently FDA approved oral drug molecule FTY720 (fingolimod hydrochloride) and its effect on dimyristoylphosphatidylcholine (DMPC) liposomes using different fluorescent molecular probes and fluorescence parameters. The variation of the steady state fluorescence intensity of 8-anilino-1-naphthalene sulfonic acid (ANS) with FTY720 in water shows an efficient micellar aggregation with the critical micellar concentration (CMC) at ~75 μM. The aggregation number calculation from steady state fluorescence quenching of pyrene shows the formation of small micellar aggregates in aqueous solution having an aggregation number of 42 ± 3 with the free energy of micellization ~-23 kJ mol(-1).

Convenient synthesis of D- and L-xylo-1,2,3,4-alkane tetrols from a D-gluco-configured common building block.

D-gluco-configured building block derived from D-(+)-gluconolactone has served as a common chiral template for the synthesis of enantiopure D- and L-xylo-configured 1,2,3,4-alkane tetrols. This has enabled synthesis of medicinally important guggultetrols and their enantiomers from a common starting point. Wittig and Grignard reactions are the key steps used for the incorporation of lipophilic chain.

Convenient strategies for the synthesis of 1,4-phenylene spaced sugars.

Two synthetic strategies have been developed for the synthesis of spaced sugars with lipophilic 1,4-phenylene core. A building block combining the usefulness of Weinreb amide functionality and modified Julia olefination reaction has been explored towards this objective. This building block offers complete flexibility in attaching any desired sugar derivative across phenylene spacer via C-C bond formation.

Propargyl bromide as an excellent alpha-bromoacetone equivalent: convenient and new route to alpha-aroylacetones.

[reaction: see text] A variety of alpha-aroylacetones 4a-g have been prepared in excellent yields following a new protocol wherein alpha-aminonitriles 1a-g as the aryl acyl anion equivalents readily react with propargyl bromide as the alpha-bromoacetone equivalent. The alkylated product undergoes one-pot unmasking of the keto functionality along with Markovnikov's hydration of the terminal alkyne with CuSO4 x 5H2O in aqueous methanol at 60 degrees C to furnish the desired target in excellent isolated yields.

Consequences of rigidity and conformational locking in a 4,4-dimethyl-1,3-dioxolane ring system during protection of internal diol.

The presence of an isopropylidene ketal protection of an internal diol in 3,4-O-isopropylidene-D-arabino-1-C-phenyl hexanone locks it in a conformation that prevents its cyclization to a pyranose ring.

Umpolung strategy for the synthesis of 2-deoxy-C-aryl glycosides: a serendipitous, efficient route for C-furanoside analogues.

[reaction: see text] 2-Deoxy-C-aryl glycosides are potential synthetic targets as they form a very vital moiety of several biologically active natural products. This paper describes a synthetic route using an umpolung strategy, which has not been explored till date. Our synthetic endeavor led to a versatile intermediate aryl ketone 10, which has paved the way for two important classes of C-glycosides, viz.