Hydrogel: Preparation, characterization, and applications: A review

Nitrogen heterocycles are among the most significant structural components of pharmaceuticals. Analysis of our database of U.S. FDA approved drugs reveals that 59% of unique small-molecule drugs contain a nitrogen heterocycle. In this review we report on the top 25 most commonly utilized nitrogen heterocycles found in pharmaceuticals. The main part of our analysis is divided into seven sections: (1) three- and four-membered heterocycles, (2) five-, (3) six-, and (4) seven- and eight-membered heterocycles, as well as (5) fused, (6) bridged bicyclic, and (7) macrocyclic nitrogen heterocycles. Each section reveals the top nitrogen heterocyclic structures and their relative impact for that ring type. For the most commonly used nitrogen heterocycles, we report detailed substitution patterns, highlight common architectural cores, and discuss unusual or rare structures.

Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals

Thiazolidinediones (TZDs) are potent insulin sensitizers that act through the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) and are highly effective oral medications for type 2 diabetes. However, their unique benefits are shadowed by the risk for fluid retention, weight gain, bone loss and congestive heart failure. This raises the question as to whether it is possible to build a safer generation of PPARγ-specific drugs that evoke fewer side effects while preserving insulin-sensitizing potential. Recent studies that have supported the continuing physiologic and therapeutic relevance of the PPARγ pathway also provide opportunities to develop newer classes of molecules that reduce or eliminate adverse effects. This review highlights key advances in understanding PPARγ signaling in energy homeostasis and metabolic disease and also provides new explanations for adverse events linked to TZD-based therapy.

PPARγ signaling and metabolism: the good, the bad and the future

The terms 'antioxidant', 'oxidative stress' and 'oxidative damage' are widely used but rarely defined. This brief review attempts to define them and to examine the ways in which oxidative stress and oxidative damage can affect cell behaviour both in vivo and in cell culture, using cancer as an example.

Biochemistry of oxidative stress

Oxidative stress is proposed as a regulatory element in ageing and various neurological disorders. The excess of oxidants causes a reduction of antioxidants, which in turn produce an oxidation–reduction imbalance in organisms. Paucity of the antioxidant system generates oxidative-stress, characterized by elevated levels of reactive species (oxygen, hydroxyl free radical, and so on). Mitochondria play a key role in ATP supply to cells via oxidative phosphorylation, as well as synthesis of essential biological molecules. Various redox reactions catalyzed by enzymes take place in the oxidative phosphorylation process. An inefficient oxidative phosphorylation may generate reactive oxygen species (ROS), leading to mitochondrial dysfunction. Mitochondrial redox metabolism, phospholipid metabolism, and proteolytic pathways are found to be the major and potential source of free radicals. A lower concentration of ROS is essential for normal cellular signaling, whereas the higher concentration and long-time exposure of ROS cause damage to cellular macromolecules such as DNA, lipids and proteins, ultimately resulting in necrosis and apoptotic cell death. Normal and proper functioning of the central nervous system (CNS) is entirely dependent on the chemical integrity of brain. It is well established that the brain consumes a large amount of oxygen and is highly rich in lipid content, becoming prone to oxidative stress. A high consumption of oxygen leads to excessive production of ROS. Apart from this, the neuronal membranes are found to be rich in polyunsaturated fatty acids, which are highly susceptible to ROS. Various neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), among others, can be the result of biochemical alteration (due to oxidative stress) in bimolecular components. There is a need to understand the processes and role of oxidative stress in neurodegenerative diseases. This review is an effort towards improving our understanding of the pivotal role played by OS in neurodegenerative disorders.

https://www.mdpi.com/1420-3049/24/8/1583/pdf

Oxidative Stress: A Key Modulator in Neurodegenerative Diseases.

In the last few decades, a lot of work has been done on thiazole ring to find new compounds related to this scaffold to act as antioxidant, analgesic, anti-inflammatory, antimicrobial, antifungal, antiviral, diuretic, anticonvulsant, neuroprotective, and antitumor or cytotoxic drug molecules with lesser side effects. This review presents the up to date development on the design and development of different thiazole derivatives.

Thiazoles: having diverse biological activities

The ocular insert represents a significant advancement in the therapy of eye disease. Ocular inserts are defined as sterile, thin, multilayered, drug-impregnated, solid or semisolid consistency devices placed into the cul-de-sac or conjuctival sac, whose size and shape are especially designed for ophthalmic application. They are composed of a polymeric support that may or may not contain a drug. The drug can later be incorporated as dispersion or a solution in the polymeric support. They offer several advantages as increased ocular residence and sustained release of medication into the eye. The insert includes a body portion sized to position within a lachrymal canaliculus of the eyelid. The inserts are classified according to their solubility as insoluble, soluble, or bioerodible inserts. The release of drug from the insert depends upon the diffusion, osmosis, and bioerosion of the drug, and this article is an attempt to present a brief about this newer drug delivery system.

Ocular inserts - Advancement in therapy of eye diseases

Protein tyrosine phosphatase 1B inhibitors as antidiabetic agents - A brief review

Objectives Fetuin-A is a circulating glycoprotein, formed in the liver. It regulates bone remodelling and calcium metabolism. Fetuin-A has adipogenic properties, so fat accumulation in the liver may be associated with higher levels of fetuin-A. Fetuin-A is an inhibitor of the phosphorylation of the insulin receptor tyrosine kinase.



Key findings  High concentrations of fetuin-A in humans causes insulin resistance. Insulin sensitivity is also found to be increased in fetuin-A knockout mice. Fetuin-A has been shown to cause insulin resistivity in type-2 diabetes mellitus and worsens the pro-atherogenic milieu.



Summary  Fetuin-A should be considered as a hepatic bio-marker. Vascular diseases like atherosclerosis are major causes of disability in patients with diabetes mellitus.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.2042-7158.2012.01561.x

Vipin Kumar Garg

Papers

Thiazoles: having diverse biological activities

Ocular inserts - Advancement in therapy of eye diseases

Protein tyrosine phosphatase 1B inhibitors as antidiabetic agents - A brief review

Role of fetuin-A in atherosclerosis associated with diabetic patients.

Platelet-activating factor (PAF)-antagonists of natural origin.