Current Organic Chemistry - Volume 20, Issue 28, 2016

By the developmentof new antineoplastic drugs addressed tospecific sites (key to tumor growth), targeted agents, which do not interfere with most normal cells have many advantages like fewer side effects (as personalized treatment), and prolonged survival time of cancer patients compared to conventional therapy. As current approaches in cancer therapy, drug delivery systems based on polymers (synthetic, natural or combinations like micelles, nanospheres, nanocapsules, nanogels, polymer-drug conjugates, polymer-drug polyplex, polymersomes) are more benefic compared to parent free drug, because of targeted effect of delivery, low toxicity, solubility in biological fluids and immunostimulatory effects. Synthetic polymers (polyesters, polyamides and polyethers) are the most used core materials for drug delivery systems, many of them being officially certified. On the other hand due to their better biocompatibility and biodegradability, the natural ones (polysaccharides and proteins) are still a hot topic on cancer therapy as drug delivery and targeting materials. This article reviews the multifunctional materials used in targeting of drugs with polymer based delivery systems as current-day data and key of future applications on cancer therapy. An increasing interest in the last decades returns to the new, engineered inorganic materials as well as to the newly optimized composites and nanocomposites.

Background: Smart stimulus-responsive nanocarriers represent a rapidly growing class of drug-delivery systems for cancer and other diseases. Objective: The alterations of redox potential between the intracellular environment and the extracellular space have been widely utilized as a trigger for delivery of therapeutic agents by smart stimulus-responsive nanocarriers. We set out to review the scientific literature. Method: Published papers between 1980 and the present day were surveyed. Results: The advantages of redox-activated smart delivery of drugs, genes, and imaging agents include: the amplitude of the redox-responsive signal; the simple chemical features needed to trigger the activation process; and the relative simplicity of preparing these nanocarriers with an integrated redox-sensitive triggering element. Redox-sensitive nanovehicles are often sensitive to glutathione (GSH) as a regulator of cellular redox potential, which is a very important redox couple in mammalian cells. Other nanostructures can be designed to respond to oxidation, which may be useful for drug-delivery to sites with oxidative stress. Conclusion: Redox-responsive nanocarriers are a prominent member of the class of smart nanocarriers, and are expected to grow importance in coming years.

RNA interference has been developed as a powerful technology for cancer therapy by intracellular delivery of siRNA and stably silences the specific related genes. Despite rapid advances regarding the intracellular delivery technologies of siRNA, cytotoxicity, survivability, and responses still generate significant challenges for the translation of basic medicine to clinical practices. In this review, biogenesis and function of siRNAs, current physical approaches for the delivery of siRNA with relative high survivability and low in cytotoxicity, and immunogenetic responses are discussed. Clinical evaluations of siRNA for cancer treatment are summarized and analyzed to point out the significant factors for applying bench technology to nanomedicine. Finally, some of the potential challenges that may limit the progress of siRNA therapeutics will be highlighted.

Current therapeutic strategies used in many types of cancer are confronted with the major problem of multidrug resistance (MDR) that can be acquired through several mechanisms. To overcome this limitation, new therapeutic options are being explored involving state-of-the-art technologies. In this respect, small- interfering RNA (siRNA) technology offers the possibility to block the expression of genes that are involved in the MDR development, improving the therapeutic index of anticancer drugs. Nanocarriers are promising delivery systems for small molecule drugs as well as for nucleic acids aiming to target specifically the cancer cells and to counteract MDR. Several types of organic and inorganic nanocarriers will be discussed in this review, together with their advantages and limitations in delivery of targeted siRNAs and cytotoxic drugs, using in vivo and in vitro experiments. Although siRNA-anticancer drug co-delivery employing nanocarriers seems to be associated with a higher antitumor activity than single drug or nucleic acid administration, more studies are needed to evaluate the efficacy and the toxicity of various nanoparticle delivery systems.

It is well known that over the time each species has directed a specific function of its metabolic activity for survival, development and perpetuation, towards a sustained seeking for a balance with the surrounding environment. In this respect, plants became a major point of interest for the pharmaceutical industry due to their capacity of synthetizing organic compounds with specific pharmacological activity, most of them as secondary metabolites. Several major classes of chemical compounds, i.e. flavones, phenolics, terpenoids and essential oils, alkaloids, lectins and polypeptides, and polyacetylenes are phytochemicals with important antimicrobial activity and, besides them, some other natural compounds involved in inter-kingdom communication, such as quorum sensing molecules or natural antimicrobial peptides. These compounds have been proposed as potential alternatives to antibiotics for fighting infectious diseases. Extensive research has been made regarding the antimicrobial efficiency for a plethora of such natural compounds, but, unfortunately, lesser importance has been given to the occurrence of microbial resistance to them. In this respect, our aim was to review the literature, highlighting the latest findings on this topic, for a comprehensive view regarding the risk of using antimicrobials from natural sources in selecting microbial resistance.

Functional biomaterials able to sense and respond to biotic and abiotic stimuli are currently clustered in the category of smart materials. Polymers represent the most investigated class of materials able to change different morphological, functional, architectural and biological properties as a feedback to an external inducing element. Although very useful in most industrial, biotechnological and ecological approaches, biopolymers bring important and intriguing impact in medicine. Numerous applications, ranging from tissue engineering to drug delivery have been recently emerged as a result of the technological progress made in the field of polymer engineering. Most interesting approaches refer to the development of intelligent targeting approaches and the design of tailored biopolymeric scaffolds utilized in therapy. The purpose of this review paper is to bring together and discuss the most recent knowledge regarding applications of smart biopolymers in biomedical scaffolding and drug delivery. Current progress made on the field of tissue engineering, cancer therapy and alternative antimicrobial approaches are highlighted.

Organocatalysis is an emerging and new field towards the direction of asymmetric synthesis and has shown a tremendous growth in 21st century. As the demand for chiral pharmaceuticals and chiral organic molecules is increasing immensely, different types of organocatalysts have been developed and used from time to time. The cinchona alkaloids and amino acid proline were the first organocatalysts used in this area followed by incredible growth in the form of urea/thiourea, DMAP, proline derivatives, squaramides, peptides, etc. The squaramide based organocatalysts are gaining impetus for asymmetric transformations and have shown remarkably good results in diverse type of reactions, wherein they usually act as linkers between two privileged skeletons. Due to its unique structural feature and wide application, squaramide holds a prominent and great potential in asymmetric synthesis. The present mini-review will briefly cover the squaramide based organocatalysts and the examples of organic reactions catalyzed by them.

9,9-Dimethyl-9H-9-silafluorene (1) is one of the hetero-polycyclic aromatic compounds containing a silicon atom in their rings. NMR observation of the reaction of 1 with superacid at low temperature showed the quantitative formation of biphenyl. The nitration of 1 with HNO3/CH2Cl2 gave 9,9-dimethyl-2-nitro-9H-9-silafluorene in 24% yield. Friedel– Crafts alkylation with tert-BuCl/FeCl3 afforded 4,4’-di-tert-butylbiphenyl in 98% yield. Bromination with Br2/Fe produced 2,2’-dibromobiphenyl in 18% yield. These electrophilic reagents were able to react through silylated arenium ions. DFT calculations suggested that 1 is likely to be protonated at the quaternary sp2 carbon C(8a) attached to the silicon atom to give a silylated arenium intermediate (1aH+), which is a σ- rather than a π-complex. Positive charge delocalization mapping based on computed Δδ13C and Δδ29Si values indicated delocalization into the limited sp2 carbons and the Si atom. A reaction of 1 with H+ to form a silolyl cation (4+) and CH4 by cleavage of the Si-CH3 bond was estimated to be comparable in energy to the formation of 1aH+. NICS(1)zz values suggested that the five-membered silolyl ring in 4+ is significantly anti-aromatic.