Mini Reviews in Medicinal Chemistry - Volume 15, Issue 7, 2015

Diabetes and its major risk factor, obesity, have become a world-wide epidemic and cause of suffering for millions of people. There is still no drug of cure for diabetes and the currently available drugs suffer from a number of limitations either due to side effects and/or loss of efficacy during prolonged use. Rutin is one of the most abundant polyphenolic compounds belonging to the flavonoid class. In the present communication, its therapeutic potential for diabetes is critically analysed by reviewing its effect on the various targets of diabetes. The multifunctional nature of rutin including action via antioxidant, anti-inflammatory, organoprotection, etc., mechanisms is outlined through review of evidences from in vitro and in vivo studies.

Along with the exuberant development of nanotechnology, a large number of nanoformulations or non materials are successfully applied in the clinics, biomedicine, cosmetics and industry. Despite some unique advantages of nanoformulations, there exist potentially worrying toxic effects, particularly those related to metal and metal-containing nanoparticles (NPs). Although various researches have been conducted to assess the metallic and metal-containing nanoparticles toxic effects, only little is known about the toxicity expressive types and evaluation, reasons and mechanisms, influencing factors and research methods of metal and metal-containing nanotoxicity. Therefore, it is of importance to acquire a better understanding of metal and metal-containing nanoparticles toxicity for medical application. This review presents a summary on the metal and metal-containing nanoparticles toxicity research progress consulting relevant literature.

Nanocellulose is an emerging sustainable biomaterial with exceptional physicochemical properties. It can be isolated from inexpensive renewable cellulosic biomass and a number of natural plant fibers have been extensively investigated as a source for such isolation. The geometrical dimensions of the prepared cellulose nanocrystals (CNCs) are however, found to vary widely, depending on the source of the cellulosic material and hydrolysis conditions. CNCs are biocompatible and biodegradable which exhibit very low cytotoxicity thus, offering a wide range of opportunities for biomedical applications. By surface modification of nanocellulose, various functional materials with tunable properties can also be developed. Over the past two decades, CNCs have garnered a significant interest as biobased reinforcing nanofiller material. This mini review will provide an overview into the production methods, sources of cellulosic fibers, surface modification strategies and drug delivery applications of the chemically or mechanically isolated nanocellulose.

Hepatitis C virus infection is a major health and economic burden worldwide. The standard of care is associated with low sustained virological response and some adverse effects. As an important component of all-oral direct-acting antiviral regimes, inhibitors of NS5A demonstrate potent pan-genotypic activity in vitro and in vivo. This review summarized the discovery and development of NS5A inhibitors, including the early chemotypes for which resistance maps to the NS5A protein, as well as first- and second-generation NS5A inhibitors and other analogues. The mechanism of action of NS5A inhibitors and related clinical trials were also described.

The identification of biologically active and potentially therapeutically useful pharmacophores from natural products has been a long-term focus in the pharmaceutical industry. The recent emergence of a worldwide obesity and Type II diabetes epidemic has increased focus upon small molecules that can modulate energy metabolism, insulin sensitivity and fat biology. Interesting preliminary work done on mangiferin (MGF), the predominant constituent of extracts of the mango plant Mangifera indica L., portends potential for this pharmacophore as a novel parent compound for treating metabolic disorders. MGF is comprised of a C-glucosylated xanthone. Owing to the xanthone chemical structure, MGF has a redox active aromatic system and has antioxidant properties. MGF exerts varied and impressive metabolic effects in animals, improving metabolic disorders. For example we have discovered that MGF is a novel activator of the mammalian pyruvate dehydrogenase complex, leading to enhancement of carbohydrate utilization in oxidative metabolism, and leading to increased insulin sensitivity in animal models of obesity and insulin resistance. In addition, recent unbiased proteomics studies revealed that MGF upregulates proteins pivotal for mitochondrial bioenergetics and downregulates proteins controlling de novo lipogenesis in liver, helping to explain protective effects of MGF in prevention of liver steatosis. Several chemical studies have achieved synthesis of MGF, suggesting possible synthetic strategies to alter its chemical structure for development of structure-activity relationship (SAR) information. Ultimately, chemical derivatization studies could lead to the eventual development of novel therapeutics based upon the parent pharmacophore structure. Here we provide comprehensive review on chemical features of MGF, synthesis of its derivatives, its pharmacokinetics and biological activities.

Traditional Chinese Medicine (TCM) has a history that can be dated back to several thousand years ago. The extant earliest medical book is Huangdi Neijing (Canon of Internal Medicine, 770 BC˜221 BC), and the earliest pharmacy monograph is Shengnong Bencao Jing (Shengnong Materia Medica, AD25˜AD220). The most influential pharmacy monograph is the Bencao Gangmu (Compendium of Materia Medica, AD1368˜AD1644). There were also many other far-reaching influencial monographs, which become the main and the most important derived resources of modern China pharmacopoeia for TCM. In this paper, we try to introduce some representative medicine and pharmacy works of ancient China, and elaborate the origin, development and improvement process of modern China pharmacopoeia, which may have referential significance for traditional and natural drugs. China Pharmacopoeia and TCM still have to face many problems in authenticity discrimination, action mechanism, and adverse reaction, etc. The improvement of China Pharmacopoeia still has room for progress with the solutions of modern analytical methods to the problems. The start-up and development of Herbalomics project will be helpful to further improve the China Pharmacopoeia, especially Chinese patented medicine and compound prescription.