Mini Reviews in Medicinal Chemistry - Volume 16, Issue 15, 2016

Compounds with the quinoline scaffold are widely investigated and offer a variety of therapeutical properties. A number of quinoline derivatives have been synthesized and among these there are glycoconjugated derivatives. Based on the interest for this family of compounds, we reviewed the different biological activities (molecular probes, antiinfective, antiproliferative, antiaggregant and antioxidant) and the potential applications in medicinal chemistry of quinoline glycoconjugates. This review wants to show an example of the glycoconjugation strategy which arose not only to modify the water solubility of the quinolines but also to influence their activity and targeting properties.

Trypanosomatids possess an unremitting requirement for distinctive endogenous sterols for their life cycle and cannot use the copious availability of cholesterol existing in their mammalian hosts. Exhaustion of endogenous sterols such as ergosterol or of its next biosynthetic product 24-ethylcholesta-5,7,22-trien- 3β-ol brings forth an inhibition of proliferation on Trypanosoma cruzi, the etiologic agent of American trypanosomiasis or Chagas disease. These metabolites are crucial; consequently, the enzymes implicated in catalyzing their formation constitute interesting molecular targets for drug design. Selective inhibition of an enzyme associated to the ergosterol biosynthesis will produce T. cruzi cell arrest. Trypanosomatids, fungi, and yeasts have need of these endogenous sterols for cell viability and growth. In fact, some effective ergosterol biosynthesis inhibitors bearing suitable pharmacokinetic properties in mammals have become putative antiparasitic agents by inducing almost complete parasitological cure in both acute and chronic experimental Chagas disease. WC-9 (compound 7; 4-phenoxyphenoxyethyl thiocyanate) holds our attention bearing in mind that this compound exhibits ED50 values at the low nanomolar range against the clinically more relevant replicative form of T. cruzi (amastigotes). The cellular activity of WC-9 is due to an exhaustion of endogenous sterols demonstrating a blockade of the biosynthetic pathway at a pre-squalene level.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the widely used medications all over the world, indicated for pain, fever, and inflammation. It is now well established that inflammation and cancer are closely linked with each other. Inflammatory mediators, like cyclooxygenase (COX), vascular endothelial growth factor (VEGF), tumor growth factor (TGF), fibroblast growth factor (FGF), chemokines, and cytokines and related genes, such as inhibitor of nuclear factor-kappa B kinase (IKK) and nuclear factor-kappa B (NF-ΚB) have been shown to be up-regulated in various cancers. Till date, numerous anticancer agents of different classes have been discovered to treat and eradicate various forms of cancer; though, limitations like cytotoxicity to normal cells and acquired tumor resistance restrict the scope of present cancer therapeutics. NSAIDs have shown to decrease the incidence, recurrence, and proliferation of various cancers, viz. colon, breast, lung, and pancreatic, etc. Therefore, the developing agents, such as NO-and H2S-releasing NSAIDs, NSAID–metal complexes, natural product–NSAID conjugates, phospho–NSAIDs, and various other NSAIDs derivatives represent the next generation therapeutics to treat both inflammation and cancer.

As one of the leading causes of deaths worldwide, cancer is posing threat despite efforts being taken to develop effective anticancer drugs. There is an increase in number of chemotherapy treatments due to growing number of manifestations causing increasing toxicities of cytotoxic agents. Almost all the anticancer agents available till date have one or the other side effects. Topoisomerases are the attractive targets to develop effective anticancer agents. There has been development of many topoisomerase inhibitors till date and has shown good anticancer activity but their side effects outnumber their anticancer potential. Hence, there is an urgent need to develop effective therapeutic agents with fewer side effects. This review deals with design and development aspect of topoisomerase inhibitors as exciting novel anticancer agents. The emphasis has been laid in particular on the new potential heterocyles as TOP inhibitors in the field of medicinal chemistry. The review discusses about the topoisomerase poisons, TOP1 suppressors, TOP inhibitors and Dual TOP 1/2 inhibitors.

Cancer is a major cause of death worldwide despite significant advances in surgery and biology. Several recent studies have suggested that there is a close connection between tumorigenesis and inflammation. Cyclooxygenase-2 (COX-2), a link between inflammation and cancer, was proposed as a prime target for cancer therapy. However, the main available COX-2 inhibitors, nonsteroidal antiinflammatory drugs (NSAIDs), have several side effects that limit their application in cancer treatment. Additional research is needed to identify drugs that can regulate COX-2 or prostaglandin E2 (PGE2) with greater efficacy. Understanding the mechanism of COX-2/PGE2-mediated cancer and inflammation would be very useful for successful drug development. Progress of research and development into the role of COX related signaling both in inflammation and tumorigenesis in recent years has been summarized and introduced in this paper. Novel drugs designed to inhibit COX-2-related cancers are discussed to provide references for further development of novel drugs.

Polysaccharides and their derivatives have opened up new industrial field because of their special biochemical functions. Their biological immune, biological inhibition, antioxidant and anticoagulant properties have begun to help people enhance their physique, the fight against aging. Molecular modification is an important way to study the structure-activity relationship of polysaccharides which should be focused on. After molecular modification, various derivatives of different types of structures and biological activities are gained. Chemical modification of polysaccharides, e.g., carboxymethylation, sulfonylation, phosphorylation, acetylation, and hydroxypropylation, cationic or other derivatives, can improve their bioavailability and applications in different biological systems.

The incidence of diabetes in developing countries in Asia has increased over the last few years. The economic development is radically changing the lifestyle of the younger generation who prefer to embrace the western lifestyle of eating high calorie fast food with minimal physical exercise. Previously, the rate of diabetes was very low but it is increasing at an alarming rate in the developing countries in Asia. Admittedly, there is paucity of literature on the prevalence of patients with type-1 diabetes in Asian developing countries due to lower field surveys and lack of quantitative data. Few contributing factors such as body mass index (BMI) and its relation with obesity and diabetes, energy dense diet, excessive caloric intake, sedentary behaviors, lifestyle and family history, gene and genomewide association of diabetes, genes and gene polymorphisms are being discussed especially with regard to the Asian population. Dynamics of the diabetes and obesity was depicted for the population of Asian developing countries with special emphasis on China and India. Diabetes has become widespread among the low-income communities. Hence, it is necessary to develop appropriate healthcare policies in order to mitigate this rampant epidemic before it is too late.