Synthesis, Antimicrobial, Antioxidant and Molecular Docking Studies on Novel 6-Methoxybenzothiazole-piperazine Derivatives with Propanamide Chain.

BACKGROUND: Infectious diseases are a major threat in the developing world and the discovery of novel antimicrobial agents remains to be crucial due to acquired resistance by the microorganisms. Additionally, various diseases can be prevented with antioxidant agents as they can eliminate the harmful effects of reactive oxygen species. OBJECTIVE: In this study, it was aimed to synthesize novel compounds bearing N-(6- methoxybenzothiazol-2-yl)-3-(4-substitued piperazinyl)propanamide backbone that had antimicrobial and antioxidant activities. Mechanisms of activity were aimed to be revealed by docking studies. METHODS: Antimicrobial activities were tested by agar-based disc diffusion assay, and antioxidant activities were determined by CUPRAC assay. RESULTS: In agar-based disc diffusion assay, the most active compounds were 2b and 2e against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans. Compounds 2e and 2j showed promising antioxidant activity in CUPRAC assay. Docking studies were performed to optimize the interactions of compounds with DNA gyrase subunit B of S. aureus. Under the light of docking studies, a new compound with potential GyrB inhibition was designed. Antioxidant activity was also supported by docking studies on superoxide dismutase 1 enzyme in which interactions with key residues were observed. CONCLUSION: Ten novel benzothiazole-piperazine derivatives were synthesized and their antimicrobial and antioxidant activities were evaluated. Superoxide dismutase 1 enzyme was suggested to be a possible target for the antioxidant activity of the series.

Simultaneous quantification of six flavonoids in four Scutellaria taxa by HPLC-DAD method

Abstract The objective of this study was to develop and validate a new HPLC method to quantify several flavonoids in the methanol extract prepared from the aerial parts of four Scutellaria L. taxa from flora of Turkey. A simple, sensitive and precise reversed phase HPLC-DAD method was developed and validated for simultaneous determination of six main flavonoids; scutellarein 7-O-β-d-glucopyranoside, hispidulin 7-O-β-d-glucuronopyranoside, apigenin 7-O-β-d-glucopyranoside, hispidulin 7-O-β-d-glucopyranoside, luteolin and apigenin. All standard compounds showed a good linearity (R 2 > 0.999) in a relatively wide concentration range (1-120 µg/ml). The limit of detection of the compounds was in the range of 0.016-1.883 µg/ml and the limit of quantification was in the range of 0.232-3.368 µg/ml. The recoveries of the selected compounds were calculated in the range of 92.20-107.93%. The amounts of flavonoids showed variation in the extracts. The developed method was found to be accurate, precise, reproducible, and can be successfully applied to identify and quantify the flavonoid composition of Scutellaria species.

Preformulation, Characterization, and In Vitro Release Studies of Caffeine-Loaded Solid Lipid Nanoparticles.

Encapsulation of active agents in solid lipid nanoparticles (SLNs) is an alternative to other controlled release systems for topical delivery. In this study, caffeine was encapsulated in SLNs to produce a delivery system with controlled release. Caffeine-loaded SLNs (Caf-SLNs) were prepared using the double emulsion method with homogenization and ultrasonication. The characterization studies were performed using dynamic light scattering (DLS), zeta potential, scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) analyses. The encapsulation efficiency tests were performed using UV spectrophotometry. In vitro release studies were conducted using a dialysis bag technique and high-performance liquid chromatography (HPLC) for the quantification of caffeine (Caf). The results from the DLS analysis showed that all formulations had a polydispersity index <0.3 with particle sizes <210 nm. The DSC and SEM results showed that Caf was dispersed in the SLNs. The encapsulation efficiency was 49.22%. The release studies indicated that after an initial burst at 3 min, the SLNs released Caf in a controlled manner over a 6-h period. Taken together, the SLNs can be used as a carrier for the topical delivery of Caf.

Safety evaluation of styrax liquidus from the viewpoint of genotoxicity and mutagenicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Styrax liquidus is a resinous exudate (balsam) obtained from the wounded trunk of the Liquidambar orientalis Mill. (Hamamelidaceae). Styrax has been used for treatment of various ailments in Turkish folk medicine such as skin problems, peptic ulcers, nocturnal enuresis, parasitic infections, antiseptic or as expectorant. AIM OF STUDY: In spite of frequent use of styrax in Turkish folk medicine as well as once as a stabilizer in perfumery industry, negative reports have been noticed by the international authority for restriction its use based on some limited evidences from an in vitro study. The aim of the present study was to evaluate the genotoxic and cytotoxic potential of styrax and its ethanolic extract using in vivo and in vitro assays, as well as an antimutagenic assay and also to determine its phenolic constituents with chromatographic analysis. MATERIALS AND METHODS: In vitro mutagenicity and antimutagenicity of styrax and its ethanolic extract were evaluated by Ames test performed on Salmonella TA98 and TA100 strains with and without metabolic activation (10- 30,000µg/plate). The genotoxicity was also studied in vivo by chromosomal aberrations assay on bone marrow of Balb C mice with different its concentrations (500-2000mg/kg body weight). Cytotoxicity has been evaluated by the MTT assay using L929 cell line. Its phenolic constituents were determined by HPLC analysis. RESULTS: Genotoxicological investigations of styrax or its ethanolic extract showed that none of the tested concentrations induced a significant increase in the revertant number of TA98 and TA100 strains with or without metabolic activation, indicating no mutagenicity to the tested strains. Also results indicated that up to 2000mg/kg body weight, styrax is not genotoxic in mammalian bone marrow chromosome aberration test in vivo. In cytotoxicity study, the IC50 values of styrax and its ethanolic extract were found to be 50.22±1.80 and 59.69±11.77µg/mL, respectively. Among the studied reference standards the major phenolic acids in styrax balsam was found to be p-coumaric acid (2.95mg/g), while in its ethanolic extract not only p-coumaric acid (11.46mg/g), but also gallic acid (1.60mg/g) were found to the main components. CONCLUSION: The findings of the present study provide scientific basis to the safety of styrax from the viewpoint of genotoxicity risk, and in fact, it was found to be beneficial against genotoxicity.

The cysteine releasing pattern of some antioxidant thiazolidine-4-carboxylic acids.

Oxidative stress that corresponds to a significant increase in free radical concentration in cells can cause considerable damage to crucial biological macromolecules if not prevented by cellular defense mechanisms. The low-molecular-weight thiol glutathione (GSH) constitutes one of the main intracellular antioxidants. It is synthesized via cysteine, an amino acid found only in limited amounts in cells because of its neurotoxicity. Thus, to ensure an efficient GSH synthesis in case of an oxidative stress, cysteine should be provided extracellularly. Yet, given its nucleophilic properties and its rapid conversion into cystine, its corresponding disulfide, cysteine presents some toxicity and therefore is usually supplemented in a prodrug approach. Here, some thiazolidine-4-carboxylic acids were synthesized and evaluated for their antioxidant properties via the DDPH and CUPRAC assays. Then, the cysteine releasing capacity of the obtained compounds was investigated in aqueous and organic medium in order to correlate the relevant antioxidant properties of the molecules with their cysteine releasing pattern. As a result, the structures' antioxidative properties were not only attributed to cysteine release but also to the thiazolidine cycle itself.

Effect of in vitro gastrointestinal digestion on the bioavailability of phenolic components and the antioxidant potentials of some Turkish fruit wines.

This study was designed to evaluate the effects of in vitro gastrointestinal simulation method on the antioxidant potentials and phenolic profile of some Turkish fruit wines and to compare the results with a Turkish red wine prepared from native grape varieties (Papazkarasi). For this purpose, blueberry, black mulberry and cherry wines were studied since they are widely consumed in Turkey. Papazkarasi wine was chosen due to the lack of studies regarding this type of wine. Antioxidant potentials of samples were measured with four different methods: DPPH radical-scavenging activity, H2O2-scavenging activity, cupric reducing capacity and total antioxidant capacity assays. The phenolic profiles of samples were evaluated by the determination of total phenolic content and HPLC-DAD analysis of seven different molecules. The results of this study provided information not only the effect of gastrointestinal digestion on parameters mentioned above, but also the bioaccessibility about the phenolic compounds found in these four different wine samples.