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

Environmental profile of the manufacturing process of perovskite photovoltaics: Harmonization of life cycle assessment studies

The development of perovskite solar cell technology is steadily increasing. The extremely high photoconversion efficiency drives factor that makes these devices so attractive for photovoltaic energy production. However, the environmental impact of this technology could represent a crucial matter for industrial development, and the sustainability of perovskite solar cell is at the center of the scientific debate. The life cycle assessment studies available in the literature evaluate the environmental profile of this technology, but the outcomes vary consistently depending on the methodological choices and assumptions made by authors. In this work, we performed the harmonization of these life cycle assessment results to understand which are effectively the environmental hotspots of the perovskite solar cell fabrication. The outcomes of this analysis allowed us to outline an environmental ranking of the profiles of the several cell configurations investigated and, most importantly, to identify the material and energy flows that mostly contribute to the technology in terms of environmental impac

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

The double face of metals: The intriguing case of chromium

Chromium (Cr) is a common element in the Earth’s crust. It may exist in different oxidation states, Cr(0), Cr(III) and Cr(VI), with Cr(III) and Cr(VI) being relatively stable and largely predominant. Chromium’s peculiarity is that its behavior relies on its valence state. Cr(III) is a trace element in humans and plays a major role in glucose and fat metabolism. The beneficial effects of Cr(III) in obesity and types 2 diabetes are known. It has been long considered an essential element, but now it has been reclassified as a nutritional supplement. On the other hand, Cr(VI) is a human carcinogen and exposure to it occurs both in occupational and environmental contexts. It induces also epigenetic effects on DNA, histone tails and microRNA; its toxicity seems to be related to its higher mobility in soil and swifter penetration through cell membranes than Cr(III). The microorganisms Acinetobacter sp. Cr1 and Pseudomonas sp. Cr13 have been suggested as a promising agent for bioremediation of Cr(VI). This review intends to underline the important role of Cr(III) for human health and the dangerousness of Cr(VI) as a toxic element. The dual and opposing roles of this metal make it particularly interesting. An overview of the recent literature is reported in support

Thallium use, toxicity, and detoxification therapy: An overview

Thallium (Tl) is released into the environment, where is present at very low levels, from both natural and anthropogenic sources. Tl is considered as one of the most toxic heavy metals; it is a non‐essential metal, present in low concentrations in humans. Tl toxicity causes dermatological and gastrointestinal diseases and disorders of the nervous system, and may even result in death. Many isotopes of Tl exist, with different uses. One of the isotopes of this metal (201Tl) is used in cardiovascular scintigraphy and for the diagnosis of malignant tumors such as breast or lung cancer and osteosarcoma bone cancer. Many Tl compounds are tasteless, colorless, and odorless. Due to these characteristics and their high toxicity, they have been used as poisons in suicides and murders for criminal purposes, as well as instances of accidental poisoning. Impaired glutathione metabolism, oxidative stress, and disruption of potassium‐regulated homeostasis may play a role in the mechanism of Tl toxicity. Solanum nigrum L. and Callitriche cophocarpa have been suggested as promising agents for the phytoremediation of Tl. In addition, macrocyclic compounds such as crown ethers (18‐crown‐6) are good candidates to absorb Tl from wastewater. Through this review, we present an update to general information about the uses and toxicity of Tl. Furthermore, the attention is focused on detoxification therapies

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

Chemopreventive molecules of coffee and beneficial metabolic effects

Among all the plant species examined, together with the food products that derive from it, coffee has a reputation that over the course of history has had a rather controversial evolution: some episodes are emblematic of the mistrust that, in the first decades of its diffusion in Europe and in the World, accompanied the drink. Coffee is obtained by infusing the powder obtained by grinding the toasted seeds of some species of tropical shrubs belonging to the genus Coffea, practiced through various techniques; although there are over 100 species, those used for food consumption are very few, and almost all of the market is aimed at only two of them: Coffea arabica and Coffea canephora, better known commercially (but improperly) with the name of Robusta. Today it can be said that the antioxidant activity of coffee, intended both as a vegetable and as a drink, has been known for some time and has been evaluated through different methods; various studies have shown that the high content of polyphenols in coffee plays an important role in its strong antioxidant action. Since 1997, the year in which the first works on this activity were presented, the concern about the potential risks related to coffee intake has rapidly diminished and a line of research has originated aimed at evaluating its therapeutic effects, especially chemopreventive, antidiabetic and anticarginogenic effects. It was immediately proposed that, at the head of the wide family of active polyphenolic compounds, there were chlorogenic acids, whose remarkable ability to prevent oxidative cell damage was immediately determined

New titanocene derivatives with high antiproliferative activity against breast cancer cells

The synthesis and characterization of some new titanocene-complexes, having a ethenyl-phenoxide or a benzyl group as substituents of the cyclopentadienyl rings, are reported. The synthesized compounds have been evaluated for their cytotoxic potential against two human breast cancer cell lines, that is: MCF7 and SkBr3. Most of these compounds have shown significant cytotoxic effects, compared to cisplatin, in MTT-based cell tests

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)

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