Current Organic Chemistry - Volume 20, Issue 25, 2016

Mosquito-borne diseases, transmitted by mosquito vectors, continue to cause illness and death in many areas of the world, especially in tropical and subtropical countries. One of the control measures of these diseases has been contingent on mosquito vector control using synthetic chemical insecticides. Due to environmental health concerns of synthetic insecticides and the rise of resistance to synthetic insecticides in mosquitoes, eco-friendly and easily biodegradable natural plant compounds that are potential insecticides are imperative for mosquito vector control and management. Over past decades, searches for insecticidal phytochemicals against mosquitoes have provided a wealth of bioactive insecticidal compounds with various types of chemical structures. This paper provides an overview of compounds from plant sources that are grouped into chemical structural groups containing potential mosquitocidal activities. Each of these groups comprises individual core structure together with large numbers of derivatives. Relationships of chemical structures and toxicities of each compound group and derivatives are highlighted. Natural plant products conferring synergistic activities on cell-based assays with pyrethroid toxicity in relation to their chemical structures are described. Understanding of relationships of bioactive compounds of plant origin belonging to different classes of chemical structures and their activities could be beneficial for effective mosquito vector control measures.

Important strategies for combating mosquito vectors include the application of larvicides. However, existing larvicides use the active substances of synthetic insecticides, which are often risky substances for both the environment and human health. Therefore new suitable alternatives have been sought, including the development of botanical larvicides based on plant essential oils (EOs). Although they show excellent larvicidal efficacy, the persistence of this efficacy is often insufficient. Such formulation methods and techniques that would allow for extending the efficacy period of the larvicides have thus been sought. Highly promising methods also include EO encapsulation. This paper summarizes the current knowledge, and it discusses the opportunities and prospects offered by EO encapsulation methods when used for the development of botanical insecticides. Although research in this field has only begun, it was possible to conclude based on existing published papers that encapsulation methods may extend the efficacy period while gradually releasing the active substances of the EOs. These methods also seem to offer excellent prospects for the future direction of the development of new botanical larvicides which are safe for the environment and health.

In the near future, a number of molecules employed in insect pest control may lose their efficacy. Pesticide resistance is an increasing problem of public health importance, and more environmental-friendly control approaches against arthropod pests of medical and veterinary relevance are urgently needed. The seed oil of neem, Azadirachta indica (Meliaceae), contains more than 100 biologically active compounds. Many formulations derived from them showed biotoxicity, antifeedancy and repellent activity against several important mosquito species, including malaria, dengue, zika and filariasis vectors. In this review, we focus on the effectiveness of neem-borne mosquitocides, with the goal to develop an ideal mosquitocide, that should be effective, eco-friendly and cheap, being preferentially derived from botanical by-products (e.g. neem cake) easily produced by countries with limited industrial facilities.

Natural products are an ideal source of chemicals for topical application to human skin, and can be a means of personal protection from the bites of mosquitoes and other arthropods. This report covers a diverse array of natural compounds, and includes descriptions of observed correlations between chemical properties and repellency. Repellent efficacy is determined by a ‘cloth-patch’ assay, which involves human volunteers testing chemicallytreated cloth in cages of adult female mosquitoes. Known concentrations of chemical are applied to cloth and the treated cloth is affixed on the arm of a volunteer. The volunteer inserts the clothed arm into a cage of adult female mosquitoes to determine if they will land and bite through the treated cloth. The Minimum Effective Dosage (MED) is determined as the threshold concentration at which 1% of the mosquitoes bite through the treated cloth. This standardized assay has been used to develop in silico models to predict the relationship between chemical and structural properties, as well as the repellent performance. This report covers the past several years of our research, which has focused on natural products and essential oils extracted from plant species from different parts of the world. Structural indicators, such as the location of an oxygen or double bond in small molecules, have been found to predict repellency. The most potent natural repellent in our studies is carvacrol; however, this compound is also a skin irritant. Thymol, as well as terpinolene, α-terpineol, eugenol, and carvacrol methyl ether were also highly efficacious against Aedes aegypti. This work may lead to the discovery of derivatives of these compounds which possess both repellent efficacy and dermal safety.

Peptide nucleic acids (PNAs) are synthetic nucleic acid mimics wherein the sugarphosphate backbone is replaced with a peptide backbone. PNAs hybridize to complementary DNA and RNA with higher affinity and superior sequence selectivity compared with DNA. An important consideration when using PNAs is the possibility of adjusting their chirality in a controlled manner using PNA monomers. The chirality of PNAs plays a major role in their ability to recognize their complementary DNA because of the intrinsically chiral character of the DNA structure. The asymmetry generated and amplified in PNAs can also be transferred to other residues, including dyes for non-linear optics and reactive species for catalysis or template synthesis, thereby paving the way to other technological applications. However, despite the increasing number of reports published thus far, no full review has yet been conducted on chiral PNA monomers. This review focuses on state-of-the-art research on the design, synthesis, properties, and applications of chiral PNA monomers. Some perspectives on future development are also raised.

Glutathione is a thiol-containing tripeptide which composed of glutamic acid, cysteine and glycine. Reduced glutathione possesses the function of anti-oxidation, toxinremoving and other crucial physiological functions. Abnormal level of it indicates the emergence of diseases such as hepatitis, pneumonia, AIDS or even cancer. Therefore real-time detection of it has the important significance of keeping normal physiological condition and monitoring certain diseases. The fluorescence technique has obvious advantages of swift response, high sensitivity and selectivity comparing with other detection methods. The detection of glutathione by fluorescent reagents has attracted much attention. In this review, we summarized fluorescent probes reported so far for glutathione according to the classification of organic and inorganic probes, including coumarin-based probes, BODIPY-based probes, quantum dots-based probes, carbon dots-based probes and so on, focusing on the detection process and mechanism. The review concluded with an outlook towards potential applications of all kinds of probes for glutathione detection.

Prolonged exposure to estrogens as hormone replacement therapy agents to relieve menopausal symptoms is linked to an increased risk of breast and other types of human cancers. Previous studies showed the carcinogenic effect of estrogens occurred through formation of carcinogenic/tumor initiating quinone metabolites. Hence, it was found that occupying both ortho-positions by substituents on the A-ring effectively prevent the quinone formation. Hence, a new substituted phenolic series of A-CD estrogen family, where the five-membered Dring is substituted with a six-membered one, was designed and synthesized. Desired compounds were prepared by stereospecific reduction of Wieland-Miescher ketone followed by coupling with lithiated protected phenols. Dehydration of corresponding alcohols afforded the alkene intermediates. Final hydrogenation removed the protecting group and selectively reduced the double bond to give the desired 9-(S)-isomer.