Mini-Reviews in Organic Chemistry - Volume 9, Issue 2, 2012

Nowadays, natural products, which could provide novel unique structures and usually have new mechanisms of action, constitute a prolific source of lead compounds for the development of novel drugs and pesticides, therefore, they play the very important roles in medicine chemistry and agrochemistry. This special issue is aimed at providing a recent update on the chemistry and modes of action of the natural products as the novel drugs and pesticides. The lead compounds from natural products optimized as the candidates by rational design-based structural modification and structure-activity relationship analysis are also addressed. Dr. Diego Gamba-Sanchez describes synthesis, biological activities, and structure-activity relationships of fumagillin and structurally related compounds. Dr. Devendra Singh Negi summarizes Himalayan plant species as pesticidal agents. Dr. Shi-Wu Chen reviews the biological and pharmacological activities, total synthesis and structure-activity relationships of triptolide and congeners. Prof. Jason T. C. Tzen presents the cardiac therapeutic effect of Magnesium Lithospermate B through both in vitro study and molecular modeling. Dr. Biswanath Das summarizes the sources, chemistry, bioactivities, and structure-activity relationships of some promising natural anticancer compounds. Prof. Gordana Stojanovic reviews the structure, biological properties, biosynthesis and structure-activity relationships of known lichen depsidones. Dr. R.S. Mann presents the recent work on natural compounds evaluated for control of insect vectors of human and animal pathogens. I would like to thank the Editorial Board of Mini Reviews in Organic Chemistry for their trust and the opportunity to organize this special issue. Meanwhile, my sincere thanks are attributed to all authors for their excellent contributions, and the anonymous peer reviewers for their constructive comments. Finally, I sincerely thank Miss Qurrat-ul-Ain Khan for her nice support and cooperation.

Cancer is one of the most prolific causes of death all around the world. Currently there is a huge focus around the globe on the identification of effective drugs against this disease. One important target is the development of new anti-angiogenic compounds. Fumagillin and other structurally related molecules are some of the most potent anti-angiogenic compounds reported to date with several currently being investigated in clinical studies. Fumagillin has been used for more than 50 years against microsporidial parasites in animals, however, angiogenesis inhibition constitutes a new activity and an important research topic, this is the reason why nowadays some teams are working to achieve an effective way to obtain fumagillin analogues with more potent anti-angiogenic activity. Here we present an overview on fumagillin and fumagillin analogues as leads products; we summarize the key structural features for antiangiogenic activity and discuss the total synthesis and synthesis of analogues and their biological activity.

The control of diseases and insect, pests for securing world is important issue for us. A significant way to find a better treatment for crop is the search for insecticidal, pesticidal and antimicrobial constituents. From many years research in biology and biochemistry has made it possible a complete new approach for the protection of plants. As part of our Botanical pesticide research project, numerous compounds from Himalayan plant species of Uttarakhand, India with potential antifeedant activity have been identified. The plants selected for complete investigations were Boenninghausenia albiflora, Skimmia anquetillia, Glycosmis arborea, Vitex negundo, Premna barbata, Callicarpa arborea and Clerodendron indicum and the pests selected were the Plecoptera reflexa, the popular defoliator Clostera cupreta, bamboo leaf roller Crypsiptya coclesalis and polyphagous pest Spodoptera litura. The extracts and pure compounds were also tested against plant pathogens, Agrobacterium tumifaciens, Pseudomonas syringae and Pactobacterium carotovorum for antibacterial activity. In all tested plants B. albiflora and S. anquetillia showed potent insecticidal and antibacterial properties. In addition all investigated plants of Rutaceae and Verbenaceae family were found to be active against S. litura pest.

Tripterygium wilfordii Hook.f. has a long history of use in traditional Chinese medicine. The diterpene triepoxide triptolide 1, as the main bioactive constituent of Tripterygium extracts, has been used to treat a variety of autoimmune, inflammation-related conditions and neurodegenerative diseases, and it also displays antiinflammatory activity, antiproliferative and apoptotic effects, antifertility and insecticidal activity. Several synthetic studies and structure-activity relationships (SAR) have been carried out on triptolide as well as others structurally related molecules. This review focused on the biological and pharmacological activities, total syntheses and their structure-activity relationships of triptolide and congeners.

The therapeutic effect of cardiac glycosides lies in their reversible inhibition on the membrane-bound Na+/K+-ATPase in human myocardium. Unfortunately, the utilization of steroidal cardiac glycosides suffers some severe adverse side effects. Magnesium lithospermateB (MLB), a derivative of caffeic acid tetramer found in Danshen (Salvia miltiorrhiza), is suggested to provide a comparable cardiac therapeutic effect by effectively inhibiting Na+/K+-ATPase via the same molecular mechanism triggered by cardiac glycosides. Molecular modeling suggests that ouabain, a cardiac glycoside, and MLB presumably bind to the same extracellular pocket of the Na+/K+-ATPase. Moreover, MLB outperforms ouabain in cell toxicity, and thus has a great potential, with extensive clinical trials, to become a safe substitute for cardiac glycosides. Neuroprotective effects of cardiac glycosides and MLB against ischemic stroke have been observed, and cumulative data suggest that effective inhibitors of Na+/K+-ATPase in the brain may be potential drugs for the treatment of ischemic stroke. Taken together, recent studies on MLB seem to promote a paradigm shift of searching potential drugs for the treatment of cardiac diseases from steroid-like compounds to non-steroid ones.

Natural products have been a rich source of anticancer compounds. Several anticancer “lead” compounds have been isolated and identified from different natural sources. These lead compounds after proper chemical modifications and bioevaluations afforded potential drugs. In the present article the sources, chemistry and bioactivities of some promising natural anticancer compounds have been discussed. The structure-activity relationship of these natural products and the discovery of useful drugs derived from them have also been highlighted.

For centuries, lichens have been used in traditional medicine and their use persists to the present day in some parts of the world. Depsidones are one of the classes of secondary metabolites which are mostly produced in lichens. Lichen depsidones have been reported to possess many biological activities, such as antitumor and antimicrobial activities. In order to point out the pharmacological potential of this class of compounds, the present article reviews the structure and biological properties of the known lichen depsidones. The biosynthesis of depsidones and the relationship between their chemical structure and biological activity is also discussed.

Natural chemicals have considerable potential for vector management because these chemicals are safer than conventional insecticides on account of their rapid environmental biodegradation and low toxicity to natural enemies, humans and other mammals and they suffer less from problems of registration difficulties. However, isolation and chemical characterization of the active compounds from plants with strong biological activities can be a tedious process compared to synthesizing new synthetic compounds because natural compounds are generally isolated in small amounts. In addition, the purity of natural products is highly variable and is dependent upon the extraction method, plant part, plant age, geographic origin and location, climate and the overall growth and health of the plant from which the chemical is extracted. Furthermore, the research and development of natural pesticides against insect vectors is constrained because of the perceived lack of economic return to the manufacturers on investment in insect vector control and also due to the difficulties in registration. Despite these difficulties, research in plant-derived pesticides has increased considerablly. In this paper we provide an overview of the compounds isolated from plants that have been evaluated for control of insect vectors of human and animal pathogens.

The industrial synthesis of pharmaceutical compounds often involves the use of organic solvents. Unfortunately, these reaction media are responsible for organic contaminations in the final product. In recent years, ionic liquids (ILs) have become the “green alternatives” of volatile organic solvents. Thus, the application of ILs instead of conventional reagents offer a new opportunity to solve problems of environmentally harmful solvents. This mini-review discusses a new application of ILs in laboratory-scale pharmaceutical synthesis.

The paper reviews synthesis of different classes of biheterocyclic five/five membered heterocyclic cyanine dyes. In this review paper detailed synthesis steps for some of the biheterocyclic five/five membered cyanine dyes were represented by equations. The synthesis covers, monomethine cyanine dyes (simple cyanine dyes), aza-monomethine cyanine dyes, dimethine cyanine dyes, trimethine cyanine dyes (carbocyanine dyes), aza-trimethine cyanine dyes, tetramethine cyanine dyes, heptamethine cyanine dyes (tricarbocyanine dyes), styryl cyanine dyes (hemi cyanine dyes), aza-styryl cyanine dyes (aza-hemi cyanine dyes) and apocyanine dyes. In addition, in the introduction section we shed some light on the use and applications of cyanine dyes.

Some recent developments concerning the syntheses, physical properties and application of metal ion containing ionic liquids (ILs) with magnetic behavior are highlighted. The component ions used so far include both inorganic and organic types, and various strategies, namely not only the proper choice but also the synthesis of anions to introduce the functionality, are presented.