Synthesis and antioxidant potential evaluation of some new thiazolidine-4-one derivatives

Introduction: Diabetes mellitus (DM) is a chronic metabolic disorder resulting from a defect in insulin secretion, insulin action, or both. It is a major and growing threat to global public health. It is estimated that more than 285 million people worldwide have DM and according to WHO statistics, in 2025 the number of those affected by this disease will have risen to over 380 million. There are two main categories of this disease. Type 1, diabetes mellitus (T1DM), also called insulin-dependent diabetes mellitus and Type 2, diabetes mellitus (T2DM), the noninsulin dependent diabetes mellitus. Type 2 is far more common and it is characterized by disorders in insulin secretion and insulin resistance. This type of disease accounts for 90 to 95% of all diabetic patients. Diabetes claims four million lives every year and it is a leading cause of blindness, kidney failure, heart attack, stroke and amputation. Motivation and objectives: The classical therapy of the T2DM mellitus has four categories of pharmacological agents: sulfonylureas and glinides, biguanides, thiazolidinediones and alpha-glucosidase inhibitors. In the development and progression of diabetes and its complications, it is generally accepted that the increased oxidative stress plays a key role too. Diabetes is usually accompanied by an increased production of free radicals or impaired antioxidant defences. The aim and the objectives of this study is synthesis and antioxidant potential evaluation of new benzyliden-thiazolidine-4-one derivatives as potential antidiabetic drugs. Materials and methods: Benzylidine-thiazolidin-4-one derivatives with xanthine structure were obtained in several steps. Starting from 1,3-dimethyl-xanthine by reaction with chloracetyl chloride the corresponding ester was obtained, that with hydrazine hydrate leads to the hydrazide appropriate. This intermediary by reaction with aryl isothiocyanates (phenyl-, 4-chloro-phenyl- and 4-bromo-phenyl isothiocyanate) lead to the thiosemicarbazides that are cyclised with chloracethyl chloride. In the last step the obtained thiazolidine-4-ones were condensed with benzaldehyde. The antioxidant potential of the compounds was evaluated using phosphomolybdenum method. Results: By chemical modulation of the 1,3-dimethyl-xanthine at nitrogen from 7 position, new thiazolidine-4-ones and benzylidene-thiazolidine-4-ones were synthesized. The intermediary and final compounds were purified by recrystalization and flash chromatography. In the IR spectra all functional groups were found which is an argument to confirm their structure. Conclusions: Starting from 1,3-dimethyl-xanthine new thiazolidine-4-one derivatives with xanthine structure were obtained. The compounds were physico-chemical characterized and their structure was confirmed by IR spectroscopy. The antioxidant potential was also evaluated

Intracellular Uptake Study of Polymeric Nanoparticles Loaded with Cardiovascular Drugs Using Confocal Laser Scanning Microscopy

Confocal laser scanning microscopy (CSLM) is a powerful microscopic tool that gives valuable morphological and functional information within cells and tissues. CLSM is non-invasive, with high-contrast scanning, a simple and fast sample preparation procedure as well as easy operation. This paper aimed to study the intracellular uptake of polymeric nanoparticles loaded with cardiovascular drugs using confocal laser scanning microscopy. Polymeric nanoparticles were prepared via nanoprecipitation method using poly(lactide-co-glycolide) (PLGA) as a biodegradable polymeric matrix and Pluronic F127 as a stabilizer. A mixture of two cardiovascular drugs—valsartan (an angiotensin II receptor antagonist drug) and amlodipine besylate (a calcium channel blocker)—was loaded in polymeric nanoparticles. The prepared polymeric nanoparticles had sizes lower than 300 nm and narrow dispersity. The cellular uptake of polymeric nanoparticles was investigated by incubating adherent mouse embryo fibroblasts (NIH 3T3) with a suspension of nanoparticles (stained previously with phthalocyanine) at three different time points. Targeted cell compartments were labeled with two fluorophores: Rhodamine B (membrane stain) and Hoechst (nucleic acid stain). Live cell imaging was performed using a confocal microscope Zeiss LSM710 with Zeiss PALM microdissection system. The intracellular uptake of polymeric nanoparticles was revealed by confocal laser scanning microscopy for each incubation time. The results suggest a possible mechanism of endocytosis and clearly a vesicular-based accumulation of the nanoparticles in the cytoplasmatic compartments

Antioxidant Properties and Cytoprotective Effect Against H2O2-Induced Cytotoxicity in Mouse Fibroblasts Cells (L-929) of Horseradish Leaves

Horseradish (Armoracia rusticana L.) is a perennial plant from the Brassicaceae family native toEurope and Asia, and globally widespread through cultivation [...

Preliminary Evaluation of Pullulan Nanoparticles Loaded with Valsartan

The objective of this paper is to develop polymeric nanoparticles loaded with a cardiovascular drug (an angiotensin II receptor blocker, valsartan). Polymeric nanoparticles were prepared via the nanoprecipitation method using pullulan acetate as biodegradable polymeric matrix and Pluronic F127 as a stabilizer. Pullulan acetate was obtained through the chemical modification of pullulan (produced through a fermentation process using the Aureobasidium pullulans strain) with dimethylformamide, pyridine and acetic anhydride. The obtained nanoparticles were characterized in terms of entrapment efficiency, size, and polydispersity index using spectrophotometric and dynamic light scattering techniques. The valsartan-loaded nanoparticles showed a good entrapment efficiency of valsartan, nanometric sizes (lower than 200 nm), and a narrow dispersity (polydispersity index below 0.2). This research revealed that pullulan and pullulan derivatives show great potential for the production of nanoparticles, with potential application in the delivery of cardiovascular agents

Encapsulation of Polyphenols from Lycium barbarum Leaves into Liposomes as a Strategy to Improve Their Delivery

This study is focused on the encapsulation of polyphenols from Lycium barbarum leaves into liposomes as a strategy to improve their delivery. Liposomes loaded with Lycium barbarum leaves extract were obtained and characterized for particle size, polydispersity, entrapment efficiency, and stability. Liposomes presented entrapment efficiency higher than 75%, nanometric particle size, narrow polydispersity, and good stability over three months at 4 °C. The liposomes containing Lycium barbarum offered a slower release of polyphenols with attenuated burst effect compared with the dissolution of free Lycium barbarum extract in phosphate buffer solution at pH 7.4. Moreover, an in vitro pretreatment of 24 h with loaded liposomes showed a cytoprotective effect against H2O2-induced cytotoxicity on L-929 mouse fibroblasts cells. These preliminary findings imply that liposomes could be successfully employed as carriers for polyphenols in pharmaceutical applications

Formulation of Pullulan Acetate Nanoparticles Loaded with 5-fluorouracil

Introduction: The aim of this study was to obtain and characterize pullulan acetate-based nanoparticles, loaded with an anticancer agent, 5-fluorouracil (5-FU) [...

Polyphenolic Extract from Sambucus ebulus L. Leaves Free and Loaded into Lipid Vesicles

The paper deals with the preparation and characterisation of hydroalcoholic polyphenolic extract from Sambucus ebulus (SE) leaves that was further loaded into three-types of lipid vesicles: liposomes, transfersomes, and ethosomes, to improve its bioavailability and achieve an optimum pharmacological effect. For Sambucus ebulus L.-loaded lipid vesicles, the entrapment efficiency, particle size, polydispersity index and stability were determined. All prepared lipid vesicles showed a good entrapment efficiency, in the range of 75–85%, nanometric size, low polydispersity indexes, and good stability over three months at 4 °C. The in vitro polyphenols released from lipid vehicles demonstrated slower kinetics when compared to the free extract dissolution in phosphate buffer solution at pH 7.4. Either free SE extract or SE extract loaded into lipid vesicles demonstrated a cytoprotective effect, even at low concentration, 5 ug/mL, against hydrogen peroxide-induced toxicity on L-929 mouse fibroblasts’ cell lines. However, the cytoprotective effect depended on the time of the cells pre-treatment with SE extract before exposure to a hydrogen peroxide solution of 50 mM concentration, requiring at least 12 h of pre-treatment with polyphenols with radical scavenging capacity