Time scale of glycation in collagen of bovine pericardium-derived bio-tissues

Glycosylation is the process of combining one or more glucose molecules (or other monosaccharides) with molecules of a different nature (which are therefore glycosylated). In biochemistry, glycosylation is catalyzed by several specific enzymes, and assumes considerable importance since it occurs mainly at the expense of proteins and phospholipids which are thus transformed into glycoproteins and glycolipids. Conversely, in diabetes and aging, glycation of proteins is a phenomenon of non-enzymatic nature and thus not easily controlled. Glycation of collagen distorts its structure, renders the extracellular matrix stiff and brittle and at the same time lowers the degradation susceptibility thereby preventing renewal. Based on models detailed in this paper and with parameters determined from experimental data, we describe the glycation of type 1 collagen in bovine pericardium derived bio-tissues, upon incubation in glucose and ribose. With arginine and lysine/hydroxylysine amino acids as the primary sites of glycation and assuming that the topological polar surface area of the sugar molecules determines the glycation rates, we modelled the glycation as a function of time and determined the glycation rate and thus the progression of glycation as well as the resulting volume increase.

Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives

A series of saccharide-modified thiadiazole sulfonamide derivatives has been designed and synthesized by the “tail approach” and evaluated for inhibitory activity against carbonic anhydrases II, IX, and XII. Most of the compounds showed high topological polar surface area (TPSA) values and excellent enzyme inhibitory activity. The impacts of some compounds on the viability of HT-29, MDA-MB-231, and MG-63 human cancer cell lines were examined under both normoxic and hypoxic conditions, and they showed certain inhibitory effects on cell viability. Moreover, it was found that the series of compounds had the ability to raise the pH of the tumor cell microenvironment. All the results proved that saccharide-modified thiadiazole sulfonamides have important research prospects for the development of CA IX inhibitors.

In Vitro Antioxidant and Anti-Glycation Activity of Resveratrol and Its Novel Triester with Trolox

Resveratrol (RSV) is well known for its many beneficial activities, but its unfavorable physicochemical properties impair its effectiveness after systemic and topical administration; thus, several strategies have been investigated to improve RSV efficacy. With this aim, in this work, we synthesized a novel RSV triester with trolox, an analogue of vitamin E with strong antioxidant activity. The new RSV derivative (RSVTR) was assayed in vitro to evaluate its antioxidant and anti-glycation activity compared to RSV. RSVTR chemical stability was assessed at pH 2.0, 6.8, and 7.2 and different storage temperatures (5 °C, 22 °C, and 37 °C). An influence of pH stronger than that of temperature on RSVTR half-life values was pointed out, and RSVTR greatest stability was observed at pH 7.2 and 5 °C. RSVTR showed a lower antioxidant ability compared to RSV (determined by the oxygen radical absorbance capacity assay) while its anti-glycation activity (evaluated using the Maillard reaction) was significantly greater than that of RSV. The improved ability to inhibit the glycation process was attributed to a better interaction of RSVTR with albumin owing to its increased topological polar surface area value and H-bond acceptor number compared to RSV. Therefore, RSVTR could be regarded as a promising anti-glycation agent worthy of further investigations.

Permeation measurement of 27 chemotherapy drugs after simulated dynamic testing on 15 surgical and examination gloves: A knowledge update

Purpose Exposure to anticancer drugs is one of the known risks for people working in specialist oncology units. Wearing gloves is a vital form of personal protection. The aim of this study was to assess, in close to real use dynamic conditions, the permeability of 15 surgical and examination gloves made from different materials when exposed to 27 anticancer drugs included in the list from international Guides and Recommendations. Methods Gloves were tested by using controlled dynamic conditions replicating flexion and extension movements that mimic typical clinical applications. Tests were performed at 37°C or at 43°C for 30 min and anticancer drugs were tested at the highest concentration used in clinical practice. To determine the permeation rate, the quantification of anticancer drugs was performed with selective and sensitive analytical methods such as inductively coupled plasma-mass spectroscopy and liquid chromatography-mass spectrometry. Results All the gloves met the EN 16523-1 European standard (1000 ng/(min.cm2)). The penetration rate of busulfan, carmustine and thiotepa exceeded the ASTM D-6978-05 American standard (10 ng/(min.cm2)) with several surgical and/or examination gloves. This standard was met in all of cases when double gloving was used. Breakage of several nitrile gloves was observed in relation with the excipient used by drugs suppliers. Conclusions Permeation is a complex multifactorial phenomenon. However, we have suggested that the thickness of the glove and three physicochemical parameters (molecular weight, topological polar surface area and hydrogen bond donor) of the drug were the main parameters affecting permeation.

MOLECULAR DOCKING AND PHARMACOKINETIC PREDICTION OF HERBAL DERIVATIVES AS MALTASE-GLUCOAMYLASE INHIBITOR

Objective: To perform molecular docking and pharmacokinetic prediction of momordicoside F2, beta-sitosterol, and cis-N-feruloyltyramine herbal derivatives as maltase-glucoamylase (MGAM) inhibitors for the treatment of diabetes.Methods: The herbal derivatives and standard drug miglitol were docked differently onto MGAM receptor using AutoDock Vina software. In addition, Lipinski’s rule, drug-likeness, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were analyzed using Molinspiration, ADMET structure–activity relationship, and prediction of activity spectra for substances online tools.Results: Docking studies reveal that momordicoside F2, beta-sitosterol, and cis-N-feruloyltyramine derivatives have high binding affinity to the MGAM receptor (−7.8, −6.8, and −6.5 Kcal/Mol, respectively) as compared to standard drug miglitol (−5.3 Kcal/Mol). In addition, all the herbal derivatives indicate good bioavailability (topological polar surface area <140 Ȧ and Nrot <10) without toxicity or mutagenic effects.Conclusion: The molecular docking and pharmacokinetic information of herbal derivatives obtained in this study can be utilized to develop novel MGAM inhibitors having antidiabetic potential with better pharmacokinetic and pharmacodynamics profile.