Among the strategies that can lead to the discovery of new drugs, the identification and use of privileged structures, molecular fragments that are able to interact with more than one target, gained particular attention, in an attempt to find new drugs in a shorter time with respect to other strategies. These structures, that have been identified mainly by empirical observations, can target only a given protein family, or can be able to interact with more, unrelated targets. This review deals with structures not covered in recent papers on this topic, and emphasizes the importance of understanding the structure target relationships, that confer the privileged status.

Recently, we demonstrated that the oligosaccharide portion of ganglioside GM1 is responsible, via direct interaction and activation of the TrkA pathway, for the ability of GM1 to promote neuritogenesis and to confer neuroprotection in Neuro2a mouse neuroblastoma cells. Recalling the knowledge that ganglioside GM1 modulates calcium channels activity, thus regulating the cytosolic calcium concentration necessary for neuronal functions, we investigated if the GM1-oligosaccharide would be able to overlap the GM1 properties in the regulation of calcium signaling, excluding a specific role played by the ceramide moiety inserted into the external layer of plasma membrane. We observed, by calcium imaging, that GM1-oligosaccharide administration to undifferentiated Neuro2a cells resulted in an increased calcium influx, which turned out to be mediated by the activation of TrkA receptor. The biochemical analysis demonstrated that PLCγ and PKC activation follows the TrkA stimulation by GM1-olig...

Background: Dual-targeting in cancer treatment by a single drug is an unconventional approach in relation to drug combinations. The rationale for the development of dualtargeting agents is to overcome incomplete efficacy and drug resistance frequently present when applying individual targeting agents. Consequently, -a more favorable outcome of cancer treatment is expected with dual-targeting strategies. Methods: We reviewed the literature, concentrating on the association between clinically relevant and/or novel dual inhibitors with the potential to modulate multidrug resistant phenotype of cancer cells, particularly the activity of P-glycoprotein. A balanced analysis of content was performed to emphasize the most important findings and optimize the structure of this review. Results: Two-hundred and forty-five papers were included in the review. The introductory part was interpreted by 9 papers. Tyrosine kinase inhibitors’ role in the inhibition of Pglycoprotein and chemosensitizati...

Purpose of review Lung being one of the vital and essential organs in the body, lung cancer is a major cause of mortality in the modern human society. Lung cancer can be broadly subdivided into nonsmall cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Although NSCLC is sometimes treated with surgery, the advanced and metastatic NSCLC and SCLC usually respond better to chemotherapy and radiation. The most important targets of these chemotherapeutic agents are various intracellular signaling molecules. The primary focus of this review article is to summarize the description of various cell signaling molecules involved in lung cancer development and their regulation by chemotherapeutic agents. Recent findings Extensive research work in recent years has identified several cellular signaling molecules that may be intricately involved in the complexity of lung cancer. Some of these cell signaling molecules are epidermal growth factor receptors, vascular endothelial growth factor receptors, mammalian target of rapamycin, mitogen-activated protein kinase phosphatase-1, peroxisome proliferator-activated receptor-gamma, matrix metalloproteinases and receptor for advanced glycation end-products. Summary The present review will strengthen our current knowledge regarding the efficacy of the above-mentioned cell signaling molecules as potential beneficial drug targets against lung cancer.

Traditional medicinal plants are a large source of natural anticancer compounds that might serve as leads for the development of novel drugs. In recent years, the scientific community in the Western world has recognized the potential of natural products, used in Traditional Chinese Medicine (TCM). Since ancient times Japanese knotweed (Fallopia japonica), has been utilized in many TCM herbal preparations as anti-cancer agent. F. japonica (FJ) is known to produce a series of bioactive secondary metabolites, including anthraquinones, stilbens, tannins, lignans, anthocyanins, phenethyl alcohols, sterols, and essential oils. Resveratrol (a stilben) and emodin (an anthraquinone) are the major active ingredients of FJ. The anticancer activity of both compounds has various molecular modes of action and mechanisms through their ability to modulate the proliferation, apoptosis, cell cycle, growth factors, protein kinase C (PKC), NF-kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) signaling cascades. This review presents an overview of the secondary metabolites of F. japonica and anticancer activities of the extract and main active principles, resveratrol and emodin. The possible molecular targets and potential chemopreventive effects are discussed.