Publications by authors named "Alexandru Sava"

4 Publications

  • Page 1 of 1

New nitric oxide-releasing indomethacin derivatives with 1,3-thiazolidine-4-one scaffold: Design, synthesis, in silico and in vitro studies.

Biomed Pharmacother 2021 Jul 6;139:111678. Epub 2021 May 6.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, "Grigore T. Popa" University of Medicine and Pharmacy of Iași, 16 University Street, Iasi, Romania. Electronic address:

In this study we present design and synthesis of nineteen new nitric oxide-releasing indomethacin derivatives with 1,3-thiazolidine-4-one scaffold (NO-IND-TZDs) (6a-s), as a new safer and efficient multi-targets strategy for inflammatory diseases. The chemical structure of all synthesized derivatives (intermediaries and finals) was proved by NMR and mass spectroscopic analysis. In order to study the selectivity of NO-IND-TZDs for COX isoenzymes (COX-1 and COX-2) a molecular docking study was performed using AutoDock 4.2.6 software. Based on docking results, COX-2 inhibitors were designed and 6o appears as the most selective derivative which showed an improved selective index compared with indomethacin (IND) and diclofenac (DCF), used as reference drugs. The biological evaluation of 6a-s, using in vitro assays has included the anti-inflammatory and antioxidant effects as well as the nitric oxide (NO) release. Referring to the anti-inflammatory effects, the most active compound was 6i, which was more active than IND and aspirin (ASP) in term of denaturation effect, on bovine serum albumin (BSA), as indirect assay to predict the anti-inflammatory effect. An appreciable anti-inflammatory effect, in reference with IND and ASP, was also showed by 6k, 6c, 6q, 6o, 6j, 6d. The antioxidant assay revealed the compound 6n as the most active, being 100 times more active than IND. The compound 6n showed also the most increase capacity to release NO, which means is safer in terms of gastro-intestinal side effects. The ADME-Tox study revealed also that the NO-IND-TZDs are generally proper for oral administration, having optimal physico-chemical and ADME properties. We can conclude that the compounds 6i and 6n are promising agents and could be included in further investigations to study in more detail their pharmaco-toxicological profile.
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http://dx.doi.org/10.1016/j.biopha.2021.111678DOI Listing
July 2021

Bulky Polyfluorinated Terphenyldiphenylboranes: Water Tolerant Lewis Acids.

Chemistry 2021 Mar 3;27(13):4327-4331. Epub 2021 Feb 3.

Institut für Anorganische Chemie und Kristallographie, Universität Bremen, Leobener Straße 7, 28359, Bremen, Germany.

Protocols for the synthesis of the bulky polyfluorinated triarylboranes 2,6-(C F ) C F B(C F ) (1), 2,6-(C F ) C F B[3,5-(CF ) C H ] (2), 2,4,6-(C F ) C H B(C F ) (3), 2,4,6-(C F ) C H B[3,5-(CF ) C H ] (4) were developed. All boranes are water tolerant and according to the Gutmann-Beckett method, 1-3 display Lewis acidities larger than that of the prominent B(C F ) .
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http://dx.doi.org/10.1002/chem.202005367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986919PMC
March 2021

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

Materials (Basel) 2019 Feb 13;12(4). Epub 2019 Feb 13.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy "Grigore T. Popa", 16 University Street, 700115 Iasi, Romania.

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 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 ( ATCC 25923, ATCC 9341) and Gram negative ( ATCC 25922) bacterial strains. The antifungal potential was investigated against Candida spp. ( ATCC 10231, ATCC MYA 2950, 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 ATCC 25923 (21.2 ± 0.43 mm) and 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 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.
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http://dx.doi.org/10.3390/ma12040558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416560PMC
February 2019

Post-Assembly Reactivity of N-Aryl Iminoboronates: Reversible Radical Coupling and Unusual B-N Dynamic Covalent Chemistry.

Chemistry 2018 Aug 25;24(46):12000-12005. Epub 2018 Jul 25.

Department of Chemistry, University of Cambridge, Lensfield Rd, Cambridge, CB2 1EW, UK.

Post-assembly reaction of a dynamic covalent iminoboronate system following addition of Cp Co resulted in the formation of a series of new reductively coupled dianionic dimers via C-C bond formation. The dimers formed as a mixture of BN-containing isomeric products: diastereomers rac and meso with coupled five-membered rings, and enantiomeric rac with a fused six-membered ring bicyclic system from C-C bond formation and rearrangement of the B-N bonds. Each isomer was identified using H NMR spectroscopy in combination with single crystal X-ray structure determination. Interestingly, interconversion between the coupled five-membered rings (rac ) and fused bicyclic systems (rac ) was found to occur through an unprecedented breaking and reforming of the B-N covalent bond. Further, the coupled products could be converted quantitatively back to their iminoboronate precursors with addition of the electron abstractor Ph C .
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http://dx.doi.org/10.1002/chem.201802790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175077PMC
August 2018