Simulated gastrointestinal digestion, intestinal permeation and plasma protein interaction of white, green, and black tea polyphenols

The gastrointestinal digestion, intestinal permeation, and plasma protein interaction of polyphenols from a single tea cultivar at different stages of processing (white, green, and black teas) were simulated. The salivary phase contained 74.8-99.5% of native polyphenols, suggesting potential bioavailability of significant amounts of antioxidants through the oral mucosal epithelium that might be gastric sensitive and/or poorly absorbed in the intestine. White tea had the highest content and provided the best intestinal bioaccessibility and bioavailability for catechins. Since most of native catechins were not absorbed, they were expected to accumulate in the intestinal lumen where a potential inhibition capacity of cellular glucose and cholesterol uptake was assumed. The permeated catechins (approximately, 2-15% of intestinal levels) significantly bound (about 37%) to plasma HDLs, suggesting a major role in cholesterol metabolism. White tea and its potential nutraceuticals could be effective in the regulation of plasma glucose and cholesterol levels

Toxicity of aflatoxin B1 towards the vitamin D receptor (VDR)

This research describes an unexpected toxicity of the aflatoxin B1 towards the vitamin D receptors. Rickets is a childhood disease, and calcium deficiency is the aetiological cause in Africa, being primarily associated with nutritional problems; in this research the contribution of aflatoxin B1 exposure during the early months of life is an interesting factor to deepen in order to prevent liver damages or the development of rickets. The results show that the expression of vitamin D receptor in osteosarcoma cell line SAOS-2 is significantly down-modulated by exposure to aflatoxin B1. This seems to suggest that Aflatoxin B1, toxic towards the vitamin D receptor, interferes with the actions of the vitamin D on calcium binding gene expression in the kidney and intestine. Experimental data indicate a 58% and 86% decrease if the cells are exposed to 5 ng/mL and 50 ng/mL of aflatoxin B1, respectively. These results seem to indicate that natural occurrence of the aflatoxin B1 and allelic variant of vitamin D receptor on (F allele) increase the risk of developing rickets of African children

Chimica farmaceutica: farmaci sistemici: Lezioni del prof. Ettore Novellino

[English]:For thousands of years, pharmacological knowledge coming from natural remedies, has been handed down from generation to generation, without any awareness of the ways in which preparations are made to face diseases. The advent of pharmaceutical chemistry and of the modern drug industry turned that lack of awareness into a scientific knowledge that changed the destiny of the human race. The twenty-eight chapters of this book, are taken from the lectures held by Professor Ettore Novellino every year in his course “Pharmaceutical Chemistry and Toxicology 2”. The first chapters address the basic notions of drugs, homeostasis, pharmacopoeia, and receptor; then, the different pharmaceutical classes are introduced by analyzing their pharmacological and chemical aspects. In particular, the structural study of the interaction between drugs and receptors or biological enzymes gives the fundamentals to connect the chemical and stereochemical properties of a compound family, with the biological activity, a correlation better known as Quantitative Structure-Activity Relationship (QSAR). Several examples of the synthesis of some of the most historically renown drugs, provided at the end of each chapter, integrate the book./ [Italiano]: Per migliaia di anni, la conoscenza farmacologica proveniente dai rimedi naturali è stata tramandata di generazione in generazione senza alcuna consapevolezza riguardo le modalità d’azione delle preparazioni allestite per affrontare le malattie. L’avvento della chimica farmaceutica e della moderna industria del farmaco ha permesso di tradurre quell’assenza di consapevolezza in un sapere scientifico capace di rivoluzionare le sorti dell’umanità. I ventotto capitoli di questo libro sono tratti dalle lezioni che il professor Ettore Novellino tiene ogni anno per il suo corso di “Chimica farmaceutica e tossicologica 2”. Il testo prende avvio dalle nozioni basilari di farmaco, omeostasi, farmacoforo e recettore e affronta le varie classi di farmaci analizzandone gli aspetti chimici e farmacologici. In particolare, lo studio strutturale dell’interazione tra il farmaco e il recettore o l’enzima biologico, fornisce al lettore le basi per correlare le proprietà chimiche e stereochimiche di una famiglia di composti all’attività biologica, correlazione meglio conosciuta come “relazione quantitativa struttura-attività” (QSAR). Completano il libro alcuni esempi, posti in chiusura di ogni capitolo, di sintesi dei farmaci storicamente più noti

Mechanistic insight into ligand binding to G-quadruplex DNA

Specific guanine-rich regions in human genome can form higher-order DNA structures called G-quadruplexes, which regulate many relevant biological processes. For instance, the formation of G-quadruplex at telomeres can alter cellular functions, inducing apoptosis. Thus, developing small molecules that are able to bind and stabilize the telomeric G-quadruplexes represents an attractive strategy for antitumor therapy. An example is 3-(benzo[d]thiazol-2-yl)-7-hydroxy-8-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)-2H-chromen-2-one (compound 1), recently identified as potent ligand of the G-quadruplex [d(TGGGGT)]4 with promising in vitro antitumor activity. The experimental observations are suggestive of a complex binding mechanism that, despite efforts, has defied full characterization. Here, we provide through metadynamics simulations a comprehensive understanding of the binding mechanism of 1 to the G-quadruplex [d(TGGGGT)]4. In our calculations, the ligand explores all the available binding sites on the DNA structure and the free-energy landscape of the whole binding process is computed. We have thus disclosed a peculiar hopping binding mechanism whereas 1 is able to bind both to the groove and to the 3' end of the G-quadruplex. Our results fully explain the available experimental data, rendering our approach of great value for further ligand/DNA studie

Thiazolidin-4-one formation. Mechanistic and synthetic aspects of the reaction of imines and mercaptoacetic acid under microwave and conventional heating

Microwave irradiation of a mixture of benzylidene-anilines and mercaptoacetic acid in benzene gives 1,3-thiazolidin-4- ones in very high yield (65–90%), whereas the same reaction performed through using the conventional method, at refluxtemperature, requires a much longer time and gives a much lower yield (25–69%). This difference seems to be due to someintermediates and by-products formed during the conventional reaction. On the basis of 1H NMR studies, two differentmechanisms, acting in benzene and in DMF, respectively, have been hypothesized for the thiazolidin-4-one system formation

Antitumor Agents. 5. Synthesis, Structure-Activity Relationships, and Biological Evaluation of Dimethyl-5H-pyridophenoxazin-5-ones, Tetrahydro-5H-benzopyridophenoxazin-5-ones, and 5H-Benzopyridophenoxazin-5-ones with Potent Antiproliferative Activity

New antiproliferative compounds, dimethyl-5H-pyrido[3,2-a]phenoxazin-5-ones (1-6), tetrahydro-5Hbenzopyrido[ 2,3-j]phenoxazin-5-ones (7-9), and 5H-benzopyrido[3,2-a]phenoxazin-5-ones (10-12) were synthesized and evaluated against representative human neoplastic cell lines. Dimethyl derivatives 1-6 were more active against carcinoma than leukemia cell lines. The tetrahydrobenzo derivatives 7-9 were scarcely active, whereas the corresponding benzo derivatives 10-12 showed notable cytotoxicity against a majority of the tested cell lines. Molecular modeling studies indicated that the high potency of 10 and 11, the most cytotoxic compounds of the whole series, could be due to the position of the condensed benzene ring, which favors ð-ð stacking interactions with purine and pyrimidine bases in the DNA active site. Biological studies suggested that 10-12 have no effect on human topoisomerases I and II and that they induce arrest at the G2/M phase

Antitumor Agents 6. Synthesis, Structure-Activity Relationships, and Biological Evaluation of Spiro[imidazolidine-4,3′-thieno[2,3-g]quinoline]-tetraones and Spiro[thieno[2,3-g]quinoline-3,5′- [1,2,4]triazinane]-tetraones with Potent Antiproliferative Activity†

Two series of quinolinquinone derivatives, 2′H-spiro[imidazolidine-4,3′-thieno[2,3-g]quinoline]-2,4′,5,9′- tetraones (2a-n) and 2H-spiro[thieno[2,3-g]quinoline-3,5′-[1,2,4]triazinane]-3′,4,6′,9-tetraones (3a-e), were designed and synthesized using the previously described ethyl 3-amino-4,9-dioxo-2,3,4,9-tetrahydrothieno[2,3- g]quinoline-3-carboxylate (1) as a starting material. All compounds were evaluated for their antiproliferative activity against a panel of representative liquid and solid human tumor cell lines and exhibit IC50 values in the micromolar/submicromolar range. Series 2 displayed higher cytotoxicity than did series 3. The nature of the substituents on both imidazoline and triazinane N1 nitrogen markedly affected the activity profile of these series. Spectrophotometric and fluorescence measurements as well as unwinding assays performed on the most cytotoxic compounds, 2c, 2g, and 2k, showed that they are nonintercalative DNA agents and inhibit the catalytic activity of Topo II in a concentration-dependent mode. 2g was the most active Topo II inhibitor with activity levels comparable to those of VP-16

Abelmoschus esculentus (L.): Bioactive Components Beneficial PropertiesFocused on Antidiabetic RoleFor Sustainable Health Applications

The main features of the okra, Abelmoschus esculentus (L.), are highlighted. The evaluation of interactions between biologically active compounds and other components of the food matrix can be considered as the first action in the investigation of potential benefits of this annual herb. Moreover, updated examples of current and innovative directions in an integrated and multidisciplinary approach are discussed, with particular attention to chemometrics. Among the main effects attributed to okra, its antidiabetic property is the focus. Finally, the use of okra in different fields will be discussed.(undefined)info:eu-repo/semantics/publishedVersio

Chemical composition and biological activity of Capparis spinosa L. from Lipari Island

Several plants belonging to the genus Capparis are the focus of growing interest due to their singular nutritional and medicinal properties. In the present study, flower bud samples from C. spinosa L. (Lipari Island, Italy) were subjected to decoction, Soxhlet, and microwave extraction techniques and the individual extracts investigated to better characterize the phytochemical and antioxidant profiles of the plant. Total phenolic and flavonoid amounts, phenolic composition, radical scavenging as well as reductive and metal chelating properties were determinated by well-established chemical and analytical procedures. Furthermore, cholinesterase inhibitory effects were evaluated by Ellman's method. Fatty acid percentage and essential oil composition were also detected by GC and GC-MS techniques respectively. Rutin was found to be the major component in the studied extracts. The Soxhlet extract exhibited the strongest radical scavenging and reductive activities as compared to the other extracts, most probably due to the highest concentration of phenolics, especially rutin. The best cholinesterase inhibitory effect was observed in the microwave extract. Palmitic acid was the most abundant fatty acid in the studied oil, whereas docosane was the major volatile compound in the essential oil. Present data corroborate the multipurpose potential of C. spinosa for designing bio-based drug formulations or functional applications. (c) 2018 SAAB. Published by Elsevier B.V. All rights reserved

Urantide Conformation and Interaction with the Urotensin-II Receptor

Urotensin II (U-II) is a disulfide bridged peptide hormone identified as the ligand of a G protein-coupled receptor. Human U-II (H-Glu-Thr-Pro-Asp-c[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH) has been described as the most potent vasoconstrictor compound identified to date. We have previously identified the compound termed urantide (H-Asp-c[Pen-Phe-DTrp-Orn-Tyr-Cys]-Val-OH), which is the most potent UT receptor (UTR) antagonist described to date. Urantide may have potential clinical value in the treatment of atherosclerosis. In the present study, we studied the conformational preferences of urantide in DPC micelles and developed a urantide/UTR interaction model. This model can help the design of novel peptides and small molecules as UTR antagonists