Ex vivo and in vivo antioxidant activity of β-hydroxy-β-arylalkanoic acids.

The interplay between oxidative stress and inflammation is implicated in many chronic diseases including Alzheimer`s disease, cardiovascular diseases, diabetes and cancer. Thirteen β-hydroxy-β-arylalkanoic acids were previously synthesized and evaluated for their anti-inflammatory activity. The aim of this study was to asses ex vivo antioxidant activity of synthesized acids, as well as ibuprofen and to identify the compounds with the most promising results for further investigation on their capacity to counteract in vivo oxidative stress triggered by inflammation.

Antioxidant Activity of Natural Phenols and Derived Hydroxylated Biphenyls.

A comparative in vitro study of the antioxidant potential of natural phenols (zingerone, curcumin, raspberry ketone, magnolol) and their synthesized derivatives was performed. The antioxidant efficiency was evaluated in blood serum obtained from healthy individuals, by means of spectrophotometry, before and after the addition of pro-oxidant -butyl hydroperoxide (TBH). Moreover, the antioxidant effect of an equimolar mixture of curcumin and zingerone was investigated.

Square wave voltammetric study of interaction between 9-acridinyl amino acid derivatives and DNA.

Electrochemical oxidation of newly synthesized acridine derivatives (ADs): PG, PA, EG and EA was studied using square wave voltammetry at a glassy carbon electrode. Oxidation occurs as an irreversible process for all ADs. The ADs interaction with DNA was investigated using multi-layer DNA electrochemical biosensor.

Natural and natural-like polyphenol compounds: antioxidant activity and potential for therapeutic application.

Introduction: Phenols are a large family of natural and synthetic compounds with known antioxidant activity. The aim of this study was to perform screening of natural and natural-like phenol monomers and their C2-symmetric dimers (hydroxylated biphenyls) in order to identify those representatives whose pharmacophores have the strongest antioxidant and the lowest prooxidant activity.

Material And Methods: Antioxidative properties of 36 compounds (monomers and their C2-symmetric dimers) were evaluated .

Synthesis and evaluation of anticancer activity of new 9-acridinyl amino acid derivatives.

A series of eleven 9-acridinyl amino acid derivatives were synthesized using a two-step procedure. Cytotoxicity was tested on the K562 and A549 cancer cell lines and normal diploid cell line MRC5 using the MTT assay. Compounds , , and were the most active, with IC values comparable to or lower than that of chemotherapeutic agent amsacrine.

An electrochemical study of 9-chloroacridine redox behavior and its interaction with double-stranded DNA.

The electrochemical behavior of 9-chloroacridine (9Cl-A), a precursor molecule for synthesis of acridine derivatives with cytostatic activity, is a complex, pH-dependent, diffusion-controlled irreversible process. Oxidation of 9Cl-A initiates with the formation of a cation radical monomer, continues via the formation of a dimer subsequent oxidation to new cation radical. Reduction of 9Cl-A produces radical monomers which are stabilized by dimer formation.

Application of biopartitioning micellar chromatography and QSRR modeling for prediction of gastrointestinal absorption and design of novel β-hydroxy-β-arylalkanoic acids.

Gastrointestinal absorption of thirteen novel β-hydroxy-β-arylalkanoic acids (HAA) with anti-inflammatory activity was predicted by use of biopartitioning micellar chromatography and compared to ibuprofen. All tested HAA have lower retention factors (k) and lower expected gastrointestinal absorption than ibuprofen, whereas derivatives with the highest values of k are 1C, 2APTF and 2C. Quantitative structure-retention relationship (QSRR) analysis was performed in order to identify molecular descriptors with the highest influence on k and ANN(k) model was selected as optimal.

In vitro prediction of gastrointestinal absorption of novel β-hydroxy-β-arylalkanoic acids using PAMPA technique.

Prediction of gastrointestinal absorption of thirteen newly synthesized β-hydroxy-β-arylalkanoic acids (HAA) and ibuprofen was performed using PAMPA test. The highest values of PAMPA parameters (%T and P) were calculated for 1C, 1B and 2C and these parameters were significantly lower in comparison to ibuprofen. QSPR analysis was performed in order to identify molecular descriptors with the highest influence on %T and -logP and to create models which could be used for the design of novel HAA with improved gastrointestinal absorption.

Docking Studies, Synthesis and Biological Evaluation of β-aryl-β-hydroxy Propanoic Acids for Anti-inflammatory Activity.

Background: Nonsteriodal anti-inflammatory drugs (NSAIDs) are numerous and widely used for more than 60 years, but there is still a strong need for developing novel selective NSAIDs. The need is justified by the fact that nonselective NSAIDs can produce serious gastric side effects and that some of the selective NSAID are withdrawn due to their cardiotoxic side effects.

Methods: Eight β-hydroxy-β-arylpropanoic acids, which belong to the arylpropanoic acid class of compounds, structurally similar to some nonsteroidal anti-inflammatory drugs (NSAIDs), were docked into 3D catalytic site of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2).

Radioprotectors - the evergreen topic.

To protect organisms from ionizing radiation (IR), and to reduce morbidity or mortality, various agents, called radioprotectors, have been utilized. Because radiation-induced cellular damage is attributed primarily to the harmful effects of free radicals, molecules with radical-scavenging properties are particularly promising as radioprotectors. Early development of such agents focused on thiol synthetic compounds, known as WR protectors, but only amifostine (WR-2721) has been used in clinical trials as an officially approved radioprotector.

An improved HPLC method with the aid of a chemometric protocol: simultaneous determination of atorvastatin and its metabolites in plasma.

The aim of the present study was to optimize a chromatographic method for the analysis of atorvastatin (acid and lactone forms), ortho- and para-hydroxyatorvastatin by using an experimental design approach. Optimization experiments were conducted through a process of screening and optimization. The purpose of a screening design is to identify the factors that have significant effects on the selected chromatographic responses, and for this purpose a full 23 factorial design was used.

The effect of lipophilicity on the hepatobiliary properties of iminodiacetic acid derivatives in the conditions of hyperbilirubinemia.

The partition coefficients (log P) of theoretically possible alkyliodinated iminodiacetic acid (IDA) derivatives and commercial IDA derivatives were calculated using two computer programs: ChemSketch Log P and ChemOffice Ultra. Newly synthesized ligands (DIETHYLIODIDA and DIISOPROPYLIODIDA) with the highest calculated log P were labeled with technetium-99m. The biodistribution and the influence of bilirubin on their biokinetics were investigated in rats and compared to corresponding results for commercial (99m)Tc-BROMIDA.

Simultaneous analysis of irbesartan and hydrochlorothiazide: an improved HPLC method with the aid of a chemometric protocol.

Experimental design method was used for HPLC determination of irbesartan and hydrochlorothiazide in combined dosage forms. The traditional approach for optimization of experiments is time-consuming, involves a large number of runs and does not allow establishing the multiple interacting parameters. The main advantages of the experimental design method include the simultaneous screening of a larger number of factors affecting response and the estimation of possible interactions.

Study of valsartan interaction with micelles as a model system for biomembranes.

In this study, the interaction of valsartan (VAL), an angiotensin II receptor antagonist, with cationic surfactant cetyltrimethylammonium bromide (CTAB) was investigated. The effect of cationic micelles on spectroscopic and acid-base properties of VAL was carried out using UV spectrophotometry at physiological conditions (pH 7.4).

Determination of fluocortolone pivalate and fluocortolone hexanoate in suppositories using reverse-phase HPLC.

Fluocortolone and its esters are synthetic corticosteroids used topically in the treatment of various skin disorders. A method that can be successfully used for the separation and determination of fluocortolone pivalate and fluocortolone hexanoate in suppositories was developed. This method is based on reverse-phase HPLC on Supelcosil LC-18 (25 cm x 4.