Bioactive properties of Clitocybe geotropa and Clitocybe nebularis

© 2020, Springer Science+Business Media, LLC, part of Springer Nature. We studied neuroprotective, antioxidative, antimicrobial and cytotoxic activity of acetone extracts of Clitocybe geotropa and Clitocybe nebularis. The ability of extracts to inhibit acetylcholinesterase was tested in order to examine neuroprotective potential of selected mushroom species. DPPH, superoxide anion and reducing power assays were used in assessing the antioxidative potential of studied mushrooms. Total phenolics content was estimated as pyrocatechol equivalent. Antimicrobial activity was evaluated through microdilution method. MTT assay was utilized in determining the cytotoxic activity of extracts. The results demonstrated that studied extracts express relatively strong neuroprotective, antioxidative, antimicrobial and moderate cytotoxic activity. The results of acetylcholinesterase inhibition for Clitocybe geotropa were in range 46.95–14.82% and for Clitocybe nebularis 36.73–12.49%. DPPH assay’s IC50 for Clitocybe geotropa were 246.58 μg/mL and for Clitocybe nebularis 46.49 μg/mL. IC50 in superoxide anion assay was 151.36 μg/mL for Clitocybe geotropa and 35.69 μg/mL for Clitocybe nebularis. In reducing power assay the absorbance for Clitocybe geotropa was in range 0.0708–0.0132 and for Clitocybe nebularis 0.0324–0.0141. Total phenolics content of Clitocybe geotropa was 95.71 µg PE/mg and of Clitocybe nebularis 93.94 µg PE/mg. MIC values for Clitocybe geotropa were in range 0.78–25 mg/mL and for Clitocybe nebularis 3.12–25 mg/mL. Cytotoxic activity of extracts was moderate, IC50 values for Clitocybe geotropa ranged from 124.2 to 155.3 μg/mL and for Clitocybe nebularis from 134.03 to 199.03 μg/mL. Both mushroom species are edible and can be referred to as functional food

Formulation, preparation and in vitro - in vivo evaluation of compression-coated tablets for the colonic-specific release of ketoprofen

ABSTRACT The aim of this study was to formulate and prepare compression-coated tablets for colonic release (CR-tablets), and to evaluate the bioavailability of ketoprofen following the administration of a single dose from mini-tablets with immediate release (IR-tablets) compared to CR-tablets. CR-tablets were prepared based on time-controlled hydroxypropylmethylcellulose K100M inner compression-coating and pH-sensitive Eudragit® L 30D-55 outer film-coating. The clinical bioavailability study consisted of two periods, in which two formulations were administered to 6 volunteers, according to a randomized cross-over design. The apparent cumulative absorption amount of ketoprofen was estimated by plasma profile deconvolution. CR-tablets were able to delay ketoprofen’s release. Compared to IR-tablets used as reference, for the CR-tablets the maximum plasma concentration (Cmax) was lower (4920.33±1626.71 ng/mL vs. 9549.50±2156.12 ng/mL for IR-tablets) and the time needed to reach Cmax (tmax) was 5.33±1.63 h for CR-tablets vs. 1.33±0.88 h for IR-tablets. In vitro-in vivo comparison of the apparent cumulative absorption amount of ketoprofen showed similar values for the two formulations. Therefore, the obtained pharmacokinetic parameters and the in vitro-in vivo comparison demonstrated the reliability of the developed pharmaceutical system and the fact that it is able to avoid the release of ketoprofen in the first part of the digestive tract

A road map for prioritizing warheads for cysteine targeting covalent inhibitors

WOS:000450383500008International audienceTargeted covalent inhibitors have become an integral part of a number of therapeutic protocols and are the subject of intense research. The mechanism of action of these compounds involves the formation of a covalent bond with protein nucleophiles, mostly cysteines. Given the abundance of cysteines in the proteome, the specificity of the covalent inhibitors is of utmost importance and requires careful optimization of the applied warheads. In most of the cysteine targeting covalent inhibitor programs the design strategy involves incorporating Michael acceptors into a ligand that is already known to bind non-covalently. In contrast, we suggest that the reactive warhead itself should be tailored to the reactivity of the specific cysteine being targeted, and we describe a strategy to achieve this goal. Here, we have extended and systematically explored the available organic chemistry toolbox and characterized a large number of warheads representing different chemistries. We demonstrate that in addition to the common Michael addition, there are other nucleophilic addition, addition-elimination, nucleophilic substitution and oxidation reactions suitable for specific covalent protein modification. Importantly, we reveal that warheads for these chemistries impact the reactivity and specificity of covalent fragments at both protein and proteome levels. By integrating surrogate reactivity and selectivity models and subsequent protein assays, we define a road map to help enable new or largely unexplored covalent chemistries for the optimization of cysteine targeting inhibitors. (C) 2018 Elsevier Masson SAS. All rights reserved