2.5 CuAAC and Metal-Free 1,3-Dipolar Huisgen Cycloadditions in Drug Discovery

Proclaimed by Sharpless in 2001, the manifesto of click chemistry philosophy shifted the focus from target-oriented to drug-like-oriented synthesis, and has enormously accelerated the drug-discovery process over the last two decades. Copper(I)-catalyzed and metal-free versions of the Huisgen 1,3-dipolar cycloaddition of azides and alkynes have become the reference click chemistry synthetic tools. These processes are adaptable to various drug-design modes such as kinetic target guided synthesis (in situ click chemistry assembling; KTGS), combinatorial chemistry/high-throughput-screening approaches, or structure-based rational projecting. Moreover, the facile click chemistry derivatization of natural or synthetic products, linking molecules or improving the stability of leads by installation of 1,2,3-triazoles, is another important stream of bioactivities. This review is intended to provide a general overview of click-chemistry-powered drug design, with dozens of successful examples resulting in the discovery of nanomolar-active 1,2,3-triazoles in every stage of drug development.

The use of plant fibers for oligosaccharide production with libraries constructed by combinatorial enzyme technology

: Combinatorial chemistry involves the chemical or biological synthesis of libraries of the diverse structural population of a template molecule and the screening for the variants expressing desirable target properties. The approach has been a focus of research activity in modern drug discovery and biotechnology for accelerating the discovery and development of novel therapeutic and bioactive compounds. This review describes the application of combinatorial chemistry in enzyme technology as a novel technique and invention developed in our laboratory to construct oligosaccharide libraries in the conversion of plant fibers. The theory, mechanism, development, and application of this combinatorial enzyme approach are presented for the first time. The potential food and non-food uses of oligosaccharides are described. Citrus pectin and wheat insoluble fiber have been used as substrates for combinatorial enzyme reactions. Generation of libraries of structural variants of pectic oligosaccharides (oligoGalA) and feruloyl oligosaccharides (FOS) demonstrates the feasibility and usefulness of the technique in the transformation of plant biomass to value-added products.

Computing Edge Metric Dimension of One-Pentagonal Carbon Nanocone

Minimum resolving sets (edge or vertex) have become an integral part of molecular topology and combinatorial chemistry. Resolving sets for a specific network provide crucial information required for the identification of each item contained in the network, uniquely. The distance between an edge e = cz and a vertex u is defined by d(e, u) = min{d(c, u), d(z, u)}. If d(e1, u) ≠ d(e2, u), then we say that the vertex u resolves (distinguishes) two edges e1 and e2 in a connected graph G. A subset of vertices RE in G is said to be an edge resolving set for G, if for every two distinct edges e1 and e2 in G we have d(e1, u) ≠ d(e2, u) for at least one vertex u ∈ RE. An edge metric basis for G is an edge resolving set with minimum cardinality and this cardinality is called the edge metric dimension edim(G) of G. In this article, we determine the edge metric dimension of one-pentagonal carbon nanocone (1-PCNC). We also show that the edge resolving set for 1-PCNC is independent.

Evaluating Aged Consumers Insight Regarding Modern Medicine and Traditional Medicine

The term traditional medicine is used to explain the traditional medical practice that has been in existence even before the advent of modern medicine. It is widely accepted and used in the prevention and treatment of physical and mental treatment as well as a social imbalance. There seem to be limits to the development of new drugs based exclusively on modern technologies. Since the 1980s, the pharmaceutical industry has tended to use high throughput synthesis and drug development based on combinatorial chemistry in developing new drugs/medicines. However, significant efforts in this direction have not resulted in the drug's expected productivity. Some large pharmaceutical companies are facing significant challenges in developing new products. Our study was to evaluate the aged population's insight regarding traditional medicine and modern medicine. It was a prospective study with duration of three months from February 2021 to April 2021. The study was conducted in the population in and around Vijayawada. A total of 400 samples were collected. Generally, nowadays people are not aware of traditional medicines even if they are inexpensive when compared to modern drugs. So we conducted this study to know the knowledge of aged peoples on traditional medicine and to know their perception regarding both modern medicine and traditional medicine. Keywords: Traditional medicine, Modern medicine, Natural, Aged, Population.

Drugs modulating apoptosis: current status

Apoptosis (programmed cell death) is a natural process that helps in removing potentially harmful cells from the body and replacing it with normal ones. Like any other process, it is also subjected to lots of deregulations and can lead to diseases like cancer, neurodegenerative conditions, multiple sclerosis, Parkinson’s disease, autoimmune disorders and inappropriate death of cells after liver failure, stroke and myocardial infarction. The knowledge of the molecular mechanisms involved in apoptosis has been progressed tremendously. Thus, therapeutics targeting apoptosis have been emerged as a novel approach for treating various disease conditions. Current approaches induce or inhibit apoptosis by targeting the key regulators of apoptosis such as Bcl2 family of proteins, TRAIL, caspases, MDM2, IAPs and p53. While many apoptotic drugs proved its efficacy in preclinical studies, some are already approved and entered the clinical setting. Numerous novel approaches such as antisense therapy, gene therapy, recombinant biologics and combinatorial chemistry are being employed to target these regulators. This review focused on the pathways of apoptosis, various therapeutic targets in apoptosis and the drugs modulating these targets.

Enzyvitands: evolvable biosynthetic and colorimetric chalices

<div><div><div><p>Designing the perfect sensor is the dream of any chemist. Since decades, a wide diversity of chemosensors targeting analytes has been explored in chemistry. Their chemical optimization is hard and with no guarantee of success. In this context, we propose a fast and easy-to-assemble colorimetric bio-chemical receptor coined Enzyvitand. It consists only of commercial chemicals. It relies on the reunification of combinatorial chemistry, first and second coordination spheres interactions and indicators displacement assays. All harbored within a protein cavity. The sensor is highly modular, cheap and evolvable. Thanks to its solved X-ray structure, we rationally designed it for the naked-eye recognition of dopamine. Hence, our sensor imitates a biological receptor for the recognition of neurotransmitters. Its immediate high versatility and evolvability is valuable for the selective detection of a wide assortment of analytes from small molecules up to micro-organisms. For the future, we anticipate new biotechnological or immunotherapeutic applications of our bio-sensor.</p></div></div></div>