Current Medicinal Chemistry - Volume 21, Issue 38, 2014

The efficacy, cellular uptake and specific transport of dietary antioxidants to target organs, tissues and cells remains the most important setback for their application in the treatment of oxidative-stress related disorders and in particular in neurodegenerative diseases, as brain targeting remains a still unsolved challenge. Nanotechnology based delivery systems can be a solution for the above mentioned problems, specifically in the case of targeting dietary antioxidants with neuroprotective activity. Nanotechnology-based delivery systems can protect antioxidants from degradation, improve their physicochemical drug-like properties and in turn their bioavailability. The impact of nanomedicine in the improvement of the performance of dietary antioxidants, as protective agents in oxidative- stress events, specifically through the use of drug delivery systems, is highlighted in this review as well as the type of nanomaterials regularly used for drug delivery purposes. From the data one can conclude that the research combining (dietary) antioxidants and nanotechnology, namely as a therapeutic solution for neurodegenerative diseases, is still in a very early stage. So, a huge research area remains to be explored that hopefully will yield new and effective neuroprotective therapeutic agents in a foreseeable future.

One of the most challenging areas in drug design is the area of new antibacterial drugs. Despite significant progress in target validation and screening programs, discovery of new antibacterial classes is not keeping pace with the growing threat of bacterial resistance. In this review we describe examples of the use of NMR spectroscopy methods in different phases of antibacterial drug design. First, several frequently used liquid and solid-state NMR techniques are presented, followed by a review and discussion of the application of NMR spectroscopy to the discovery of new antibacterial agents.

Antimicrobial diazanaphthalenes are indispensable in the treatment of various infections. The quinoxaline scaffold possesses unique physicochemical properties and provides a possibility of a great number of targeted modifications. Quinoxaline-based compounds have a wide range of promising biological properties; therefore a special attention is paid to them for research and designing of new drugs. In fact, quinoxaline can be considered as a privileged structure. The scaffold can be easily and rapidly constructed, which emphasizes the significance of this favourable structure. The review is focused on recently reported potential antibacterial, antimycobacterial, antifungal and antiprotozoal agents derived from the quinoxaline scaffold, their mechanism of action and structure-activity relationships. A brief classification of synthetic pathways of quinoxaline derivatives is provided too.

The epidermal growth factor receptor (EGFR) family includes four structurally related receptor tyrosine kinases, termed as HER1 (EGFR, erbB1), HER2 (erbB2), HER3 (erbB3), and HER4 (erbB4). Given its intimate role in the development of several solid tumors, excessive HER signaling provides a unique opportunity for anticancer intervention. Along with extensive pharmacological studies validating the therapeutic potential of targeting the EGFR family for cancer therapy, kinase inhibitors of this family are continuously coming up and entering clinical studies. Herein, we review the EGFR family small molecule kinase inhibitors which have been approved or progressed into clinical studies, mainly focusing on their mechanisms of action, structure-activity relationships, binding modes, synthetic routes, and clinical status.

p38 mitogen-activated protein kinases (p38 MAPK, p38) consist of 4 subunits: p38α, p38β, p38γ and p38δ. They play a well-recognized role in regulating intracellular signaling transduction in mammalian cells. p38 MAPK induces a variety of intracellular responses associated with neuropathic pain and other chronic pain. Thus, specific targeting p38 MAPK molecule and its signaling pathway represent potential therapeutic strategies for pain management. Based on the understanding of the crystal structure, biological functions and its signaling pathway of p38 MAPK, chemically synthesized p38 MAPK inhibitors have become available. Natural products and biological components may also serve as potential p38 MAPK inhibitors. To this end, we will evaluate their potential for chronic pain management.