Glutathione (GSH) is a tripeptide, which has many biological roles including protection against reactive oxygen and nitrogen species. The primary goal of this paper is to characterize the principal mechanisms of the protective role of GSH against reactive species and electrophiles. The ancillary goals are to provide up-to-date knowledge of GSH biosynthesis, hydrolysis, and utilization; intracellular compartmentalization and interorgan transfer; elimination of endogenously produced toxicants; involvement in metal homeostasis; glutathione-related enzymes and their regulation; glutathionylation of sulfhydryls. Individual sections are devoted to the relationships between GSH homeostasis and pathologies as well as to developed research tools and pharmacological approaches to manipulating GSH levels. Special attention is paid to compounds mainly of a natural origin (phytochemicals) which affect GSH-related processes. The paper provides starting points for development of novel tools and provides a hypothesis for investigation of the physiology and biochemistry of glutathione with a focus on human and animal health.

https://downloads.hindawi.com/archive/2012/736837.pdf

Glutathione Homeostasis and Functions: Potential Targets forMedical Interventions

Indole synthesis: a review and proposed classification

Indoles, both naturally occurring and synthetic, exhibit wide-ranging biological activity. Unusual and complex molecular architectures occur among their natural derivatives. As a result, this important ring system continues to attract attention from the international chemical community, and new methodologies for the construction of this ever relevant heteroaromatic ring continue to be developed. Unfortunately, many methods frequently start from ortho-substituted anilines, thereby greatly restricting the availability of starting materials. A more general approach would start from a mono-functionalized arene such as an aniline or halobenzene, followed by cyclization with C–C or C–N bond formation to an unactivated C–H bond. Such methods are the subject of this perspective.

http://www.chtf.stuba.sk/~szolcsanyi/education/files/Chemia%20heterocyklickych%20zlucenin/Prednaska%202/Doplnkove%20studijne%20materialy/Indole/Indole%20synthesis%20%96%20something%20old,%20something%20new.pdf

Indole synthesis – something old, something new

In recent years, transition metal-catalyzed direct (hetero)arylation reactions of heteroarenes with (hetero)aryl halides and pseudohalides have received significant attention as eco-friendly and economic alternatives to classical methods for the construction of heteroaryl-(hetero)aryl CC bonds by transition metal-catalyzed cross-couplings involving the use of stoichiometric amounts of organometallic reagents. This critical review with 430 references covers the results obtained in the period January 2009 to February 2013 in the area of the transition metal-catalyzed direct inter- and intramolecular (hetero)arylation reactions of heteroarenes containing one heteroatom. Particular attention has been given to illustrate chemo- and site selectivity aspects of these reactions as well applications of these CC bond forming reactions in the synthesis of pharmaceutically relevant compounds, natural products and their analogues and precursors. The most recent advancements into the mechanism(s) of these reactions have also been briefly reported.

Cross‐Coupling of Heteroarenes by CH Functionalization: Recent Progress towards Direct Arylation and Heteroarylation Reactions Involving Heteroarenes Containing One Heteroatom

Accumulating lines of experimental evidence have revealed that hypoxia-inducible factors, HIF-1α and HIF-2α, are key regulators of the adaptation of cancer- and metastasis-initiating cells and their differentiated progenies to oxygen and nutrient deprivation during cancer progression under normoxic and hypoxic conditions. Particularly, the sustained stimulation of epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), stem cell factor (SCF) receptor KIT, transforming growth factor-β receptors (TGF-βRs) and Notch and their downstream signalling elements such as phosphatidylinositol 3′-kinase (PI3K)/Akt/molecular target of rapamycin (mTOR) may lead to an enhanced activity of HIFs. Moreover, the up-regulation of HIFs in cancer cells may also occur in the hypoxic intratumoral regions formed within primary and secondary neoplasms as well as in leukaemic cells and metastatic prostate and breast cancer cells homing in the hypoxic endosteal niche of bone marrow. The activated HIFs may induce the expression of numerous gene products such as induced pluripotency-associated transcription factors (Oct-3/4, Nanog and Sox-2), glycolysis- and epithelial-mesenchymal transition (EMT) programme-associated molecules, including CXC chemokine receptor 4 (CXCR4), snail and twist, microRNAs and angiogenic factors such as vascular endothelial growth factor (VEGF). These gene products in turn can play critical roles for high self-renewal ability, survival, altered energy metabolism, invasion and metastases of cancer cells, angiogenic switch and treatment resistance. Consequently, the targeting of HIF signalling network and altered metabolic pathways represents new promising strategies to eradicate the total mass of cancer cells and improve the efficacy of current therapies against aggressive and metastatic cancers and prevent disease relapse.

https://digitalcommons.unmc.edu/cgi/viewcontent.cgi?article=1081&context=com_bio_articles

Hypoxia-inducing factors as master regulators of stemness properties and altered metabolism of cancer- and metastasis-initiating cells.

Novel approach to arylhydrazones, the precursor for Fischer indole synthesis, via diazo esters derived from α-amino acid esters

Novel method for synthesis of aryl hydrazones from α-diazo esters: scope and limitations of nucleophiles

Glyoxalase-I is a novel target against Bcr-Abl + leukemic cells acquiring stem-like characteristics in a hypoxic environment

/pdf/glyoxalase-i-is-a-novel-target-against-bcr-abl-leukemic-26essjfym8.pdf

Glyoxalase-I is a novel target against Bcr-Abl+ leukemic cells acquiring stem-like characteristics in a hypoxic environment.

Development of novel pyrrole synthesis for the preparation of intermediates of bioactive pyrrole alkaloids

Versatile electrophiles N-acylhydrazones are synthesized via diazotization, reduction, and acylation of alpha-amino acid esters. Reduction of diazo esters with L-selectride or tributylphosphine affords the corresponding hydrazones in good yields. Both reducing agents give anti-hydrazones as the major product although the reactivity of each reductant is slightly different. The resulting hydrazones are acylated to give N-acylhydrazones, which are subjected to further reactions to give 1,3,4-oxadiazin-6-ones that serve as useful synthetic intermediates for the Diels-Alder reaction.

Eiko Yasui

Papers

Novel approach to arylhydrazones, the precursor for Fischer indole synthesis, via diazo esters derived from α-amino acid esters

Novel method for synthesis of aryl hydrazones from α-diazo esters: scope and limitations of nucleophiles

Glyoxalase-I is a novel target against Bcr-Abl+ leukemic cells acquiring stem-like characteristics in a hypoxic environment.

Development of novel pyrrole synthesis for the preparation of intermediates of bioactive pyrrole alkaloids

New Entry for Synthesis of N- Acylhydrazones, Pyridazinones, and 1,3,4-Oxadiazin-6-ones from α-Amino Acid Esters