Carbazole Derivatives: A Promising Scenario for Breast Cancer Treatment

Chemotherapeutics used in cancer treatment may elicit pleiotropic effects interfering, for instance, directly on DNA metabolism or on endoplasmic organelles functions. Recently there has been a trend towards the use of molecular-targeted therapies as alternative treatments of cancer, arising from the need to overcome the onset of undesired side effects or drug-resistance. Thus, a major challenge is the design and synthesis of new agents able to interact with specific cellular components, often over-expressed or altered in cancerous cells, such as telomerase and topoisomerase or protein kinases, with reduced toxicity at effective doses. The main molecular targets for the development of new anticancer drugs include: cell surface receptors, signal transduction pathways, enzymes, gene transcription, ubiquitin-proteasome/heat shock proteins, and anti-angiogenic agents. Several natural or synthetic polycyclic molecules with carbazolic nucleus, which show attractive drug-like properties, were identified with the aim to increase their biological activities and their specificity, obtaining cytotoxic agents effective in a panel of cancer cell lines. The cytotoxic profile of these compounds has been assessed using several in vitro assays as, for instance, MTT, colony formation, and flow cytometry assays and some of these compounds showed an interesting profile at sub-micromolar concentrations. The usefulness of some carbazole derivatives has been demonstrated, as well, in preclinical studies. - See more at: http://www.eurekaselect.com/132941/article#sthash.sPhGDh36.dpu

"COOPETITION" FOR CULTURAL TOURISM: AN ACCOUNTING HISTORY PERSPECTIVE

This research proposes an accounting history perspective on “coopetition”—a competitive approach based on cooperation—in the cultural tourism sector. The analysis is based on the International Museums Campaigns proclaimed by UNESCO in 1956 and 1957 and investigates the contribution of the Egyptian Museum of Turin, in the context of the local tourism system, in constructing an event and its related communication campaign. The purpose is to highlight, through accounting documents, the importance of coopetition in stimulating visitors’ presence and reaching higher shared socio-economic results

Diarylureas as antitumor agents

The diarylurea is a scaffold of great importance in medicinal chemistry as it is present in numerous heterocyclic compounds with antithrombotic, antimalarial, antibacterial, and anti-inflammatory properties. Some diarylureas, serine-threonine kinase or tyrosine kinase inhibitors, were recently reported in literature. The first to come into the market as an anticancer agent was sorafenib, followed by some others. In this review, we survey progress over the past 10 years in the development of new diarylureas as anticancer agents

Changes in the amounts of cytoskeletal proteins within the perikarya and axons of regenerating frog motoneurons

Changes in the amounts of tubulin, actin, and neurofilament polypeptides were found in regenerating motoneurons of grass frogs during the period of axonal elongation. Ventral roots 9 and 10 were transected unilaterally about 7 mm from the spinal cord. 35 d later, [3H]colchicine binding had decreased in the proximal stumps to approximately one-half of contralateral control values, well before the regenerating motor axons had reinnervated skeletal muscles of the hind limb. [3H]colchicine binding did not change significantly in the operated halves of the 9th and 10th spinal cord segments over a 75-d period. The relative amounts of actin, tubulin, and neurofilament polypeptides in the operated ventral roots were measured by quantitative densitometry of stained two-dimensional electrophoretic gels. Alpha-tubulin, beta-tubulin, and the 68,000 molecular weight subunit of neurofilaments (NF68) decreased within the transected ventral roots to 78%, 57%, and less than 15% of control values, respectively. The amount of actin increased to 132% of control values within the operated ventral roots, although this change was not statistically significant. Opposite changes were found within motoneuronal cell bodies isolated from the spinal cord. The relative amounts of alpha-tubulin, beta-tubulin and NF68 within axotomized perikarya increased, respectively, to 191%, 146%, and 144% of that in control perikarya isolated from the contralateral side of the spinal cord. Thus, the changes in NF68 and tubulin did not occur uniformly throughout the injured cells. The possible structural and functional consequences of these changes are discussed

Catalytic and biological activity of silver and gold complexes stabilized by nhc with hydroxy derivatives on nitrogen atoms

In this paper is reported the synthesis of N,N′ hydroxy derivative of NHC silver (3a–4a) and gold(I) (3b–4b) complexes of general formula [M(NHC)2 ]+ [MX2 ]−. All compounds were characterized by spectroscopic and analytic techniques. The complexes turned out to be effective in both catalytic and biological applications. They catalyzed the coupling of aldehyde, piperidine, and phenylacetylene in A3-reaction to produce propargylamines and showed antimicrobial activity. In fact, minimal inhibition concentration (MIC) tests with Gram-positive and Gram-negative bacteria demonstrated that the silver compounds are selective toward E. coli, whereas the gold analogues are active against S. aureus. Moreover, the N,N′ hydroxy derivative of NHC silver complexes 3a and 4a exhibited good anticancer activity on the HeLA cancer cells (3a-IC50 = 12.2 ± 0.1 µM, 4a-IC50 = 11.9 ± 1.2 µM), whereas gold complex 4b displayed good anticancer activity towards the MCF-7 cells (IC50 = 12.2 ± 1.2 µM)

Multidrug Resistance (MDR): A Widespread Phenomenon in Pharmacological Therapies

Multidrug resistance is a leading concern in public health. It describes a complex phenotype whose predominant feature is resistance to a wide range of structurally unrelated cytotoxic compounds, many of which are anticancer agents. Multidrug resistance may be also related to antimicrobial drugs, and is known to be one of the most serious global public health threats of this century. Indeed, this phenomenon has increased both mortality and morbidity as a consequence of treatment failures and its incidence in healthcare costs. The large amounts of antibiotics used in human therapies, as well as for farm animals and even for fishes in aquaculture, resulted in the selection of pathogenic bacteria resistant to multiple drugs. It is not negligible that the ongoing COVID‐19 pandemic may further contribute to antimicrobial resistance. In this paper, multidrug resistance and antimicrobial resistance are underlined, focusing on the therapeutic options to overcome these obstacles in drug treatments. Lastly, some recent studies on nanodrug delivery systems have been reviewed since they may represent a significant approach for overcoming resistance

Schiff bases: Interesting scaffolds with promising antitumoral properties

Schiff bases, named after Hugo Schiff, are highly reactive organic compounds broadly used as pigments and dyes, catalysts, intermediates in organic synthesis, and polymer stabilizers. Lots of Schiff bases are described in the literature for various biological activities, including antimalarial, antibacterial, antifungal, anti-inflammatory, and antiviral. Schiff bases are also known for their ability to form complexes with several metals. Very often, complexes of Schiff bases with metals and Schiff bases alone have demonstrated interesting antitumor activity. Given the innumerable vastness of data regarding antitumor activity of all these compounds, we focused our attention on mono-and bis-Schiff bases alone as antitumor agents. We will highlight the most significant examples of compounds belonging to this class reported in the literature

Simple thalidomide analogs in melanoma: Synthesis and biological activity

Thalidomide is an old well-known drug that is still of clinical interest, despite its terato-genic activities, due to its antiangiogenic and immunomodulatory properties. Therefore, efforts to design safer and effective thalidomide analogs are continually ongoing. Research studies on thalidomide analogs have revealed that the phthalimide ring system is an essential pharmacophoric fragment; thus, many phthalimidic compounds have been synthesized and evaluated as anticancer drug candidates. In this study, a panel of selected in vitro assays, performed on a small series of phthalimide derivatives, allowed us to characterize compound 2k as a good anticancer agent, acting on A2058 melanoma cell line, which causes cell death by apoptosis due to its capability to inhibit tubulin polymerization. The obtained data were confirmed by in silico assays. No cytotoxic effects on normal cells have been detected for this compound that proves to be a valid candidate for further investigations to achieve new insights on possible mechanism of action of this class of compounds as anticancer drugs

Novel anti-obesity quercetin-derived Q2 prevents metabolic disorders in rats fed with high-fat diet

Objective: Obesity is often accompanied by an increased morbidity and mortality due to an increase of the cardiovascular disease risk factors, diabetes mellitus and dyslipidemia. Research is constantly working on protective molecules against obesity. In the present study, a novel Quercetin derivative Q2 was synthesized to overcome the poor bioavailability and low stability of Quercetin, a natural flavonoid with antioxidative and antiobesity properties. Methods: Rats were fed (12ws) with normodiet (fat:INS; 6.2%), High Fat Diet (fat:60%), HFDINS; +INS; Q2 in water (500INS; nM). Metabolic and anthropometric parameters were measured. 3T3-L1 preadipocytes were incubated with Q2 (1-25μM) and the differentiation program was evaluated by lipid accumulation through ORO staining. Gene and protein expression levels were assessed by RT-PCR and Western blot analysis. Results: Compared to HFD, HFDINS; +INS; Q2 rats showed reduced body weight, abdominal obesity, dyslipidemia and improved glucose tolerance. This is associated to lower adipose and liver modifications compared to hypertrophy and steatosis observed in HFD. In 3T3-L1 cells, lipid accumulation was significantly impaired by treatment with Q2. Indeed, Q2 significantly decreased the expression of the main adipogenic markers, c/EBPα and PPARγ both at mRNA and protein level. Conclusions: Our results indicate that Q2 markedly decreases differentiation of 3T3-L1 preadipocytes and contributes to prevent metabolic disorders as well as adipose and liver alterations typical of severe obesity induced by a HFD

Pomegranate: Nutraceutical with promising benefits on human health

Pomegranate is an old plant made up by flowers, roots, fruits and leaves, native to Central Asia and principally cultivated in the Mediterranean and California (although now widespread almost all over the globe). The current use of this precious plant regards not only the exteriority of the fruit (employed also for ornamental purpose) but especially the nutritional and, still potential, health benefits that come out from the various parts composing this one (carpellary membranes, arils, seeds and bark). Indeed, the phytochemical composition of the fruit abounds in compounds (flavonoids, ellagitannins, proanthocyanidins, mineral salts, vitamins, lipids, organic acids) presenting a significant biological and nutraceutical value. For these reasons, pomegranate interest is increased over the years as the object of study for many research groups, particularly in the pharmaceutical sector. Specifically, in-depth studies of its biological and functional properties and the research of new formulations could be applied to a wide spectrum of diseases including neoplastic, cardiovascular, viral, inflammatory, metabolic, microbial, intestinal, reproductive and skin diseases. In this review, considering the increasing scientific and commercial interest of nutraceuticals, we reported an update of the investigations concerning the health-promoting properties of pomegranate and its bioactive compounds against principal human pathologies