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

A Sustainable Approach to a Cleaner Production of Antimicrobial and Biocompatible Protein Fibers

This study presents the production, characterization, and application of celandine (Chelidonium majus L.) extracts (aqueous, acidic, alcoholic, and ultrasound) on wool fibers and their characterization. The study aims to obtain an ecologically dyed wool support that possesses biocompatible and antimicrobial activities. The plant extracts were characterized based on pH, total polyphenol content, and berberine content. Ecologically dyed wool supports were characterized based on scanning electron microscopy, levelness index, color measurements, contact angle indirect biocompatibility, and antibacterial analysis. According to the obtained results, celandine extract can be considered a potential candidate for the sustainable dyeing and functionalization of wool fibers

Design, Synthesis, In Silico and In Vitro Studies for New Nitric Oxide-Releasing Indomethacin Derivatives with 1,3,4-Oxadiazole-2-thiol Scaffold

Starting from indomethacin (IND), one of the most prescribed non-steroidal anti-inflammatory drugs (NSAIDs), new nitric oxide-releasing indomethacin derivatives with 1,3,4-oxadiazole-2-thiol scaffold (NO-IND-OXDs, 8a–p) have been developed as a safer and more efficient multitarget therapeutic strategy. The successful synthesis of designed compounds (intermediaries and finals) was proved by complete spectroscopic analyses. In order to study the in silico interaction of NO-IND-OXDs with cyclooxygenase isoenzymes, a molecular docking study, using AutoDock 4.2.6 software, was performed. Moreover, their biological characterization, based on in vitro assays, in terms of thermal denaturation of serum proteins, antioxidant effects and the NO releasing capacity, was also performed. Based on docking results, 8k, 8l and 8m proved to be the best interaction for the COX-2 (cyclooxygense-2) target site, with an improved docking score compared with celecoxib. Referring to the thermal denaturation of serum proteins and antioxidant effects, all the tested compounds were more active than IND and aspirin, used as references. In addition, the compounds 8c, 8h, 8i, 8m, 8n and 8o showed increased capacity to release NO, which means they are safer in terms of gastrointestinal side effects

Formulation and Characterization of New Polymeric Systems Based on Chitosan and Xanthine Derivatives with Thiazolidin-4-One Scaffold

In the past many research studies have focused on the thiazolidine-4-one scaffold, due to the important biological effects associated with its heterocycle. This scaffold is present in the structure of many synthetic compounds, which showed significant biological effects such as antimicrobial, antifungal, antioxidant, anti-inflammatory, analgesic, antidiabetic effects. It was also identified in natural compounds, such as actithiazic acid, isolated from Streptomyces strains. Starting from this scaffold new xanthine derivatives have been synthetized and evaluated for their antibacterial and antifungal effects. The antibacterial action was investigated against Gram positive (Staphyloccoccus aureus ATCC 25923, Sarcina lutea ATCC 9341) and Gram negative (Escherichia coli ATCC 25922) bacterial strains. The antifungal potential was investigated against Candida spp. (Candida albicans ATCC 10231, Candida glabrata ATCC MYA 2950, Candida parapsilosis ATCC 22019). In order to improve the antimicrobial activity, the most active xanthine derivatives with thiazolidine-4-one scaffold (XTDs: 6c, 6e, 6f, 6k) were included in a chitosan based polymeric matrix (CS). The developed polymeric systems (CS-XTDs) were characterized in terms of morphological (aspect, particle size), physic-chemical properties (swelling degree), antibacterial and antifungal activities, toxicity, and biological functions (bioactive compounds loading, entrapment efficiency). The presence of xanthine-thiazolidine-4-one derivatives into the chitosan matrix was confirmed using Fourier transform infrared (FT-IR) analysis. The size of developed polymeric systems, CS-XTDs, ranged between 614 µm and 855 µm, in a dry state. The XTDs were encapsulated into the chitosan matrix with very good loading efficiency, the highest entrapment efficiency being recorded for CS-6k, which ranged between 87.86 ± 1.25% and 93.91 ± 1.41%, depending of the concentration of 6k. The CS-XTDs systems showed an improved antimicrobial effect with respect to the corresponding XTDs. Good results were obtained for CS-6f, for which the effects on Staphylococcus aureus ATCC 25923 (21.2 ± 0.43 mm) and Sarcina lutea ATCC 9341 (25.1 ± 0.28 mm) were comparable with those of ciprofloxacin (25.1 ± 0.08 mm/25.0 ± 0.1 mm), which were used as the control. The CS-6f showed a notable antifungal effect, especially on Candida parapsilosis ATCC 22019 (18.4 ± 0.42 mm), the effect being comparable to those of nystatin (20.1 ± 0.09 mm), used as the control. Based on the obtained results these polymeric systems, consisting of thiazolidine-4-one derivatives loaded with chitosan microparticles, could have important applications in the food field as multifunctional (antimicrobial, antifungal, antioxidant) packaging materials