Evaluation of Anti-Alzheimer Activity of Synthetic Coumarins by Combination of in Vitro and in Silico Approaches.

Series of synthetic coumarin derivatives (1-16) were tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), two enzymes linked to the pathology of Alzheimer's disease (AD). Compound 16 was the most active AChE inhibitor with IC50 32.23±2.91 µM, while the reference (galantamine) had IC50 =1.85±0.12 µM. Compounds 9 (IC50 75.14±1.82 µM), 13 (IC50 =16.14±0.43 µM), were determined to be stronger BChE inhibitors than the reference galantamine (IC50 =93.53±2.23 µM). The IC50 value of compound 16 for BChE inhibition (IC50 =126.56±11.96 µM) was slightly higher than galantamine. The atomic interactions between the ligands and the key amino acids inside the binding cavities were simulated to determine their ligand-binding positions and free energies. The three inhibitory coumarins (9, 13, 16) were next tested for their effects on the genes associated with AD using human neuroblastoma (SH-SY5Y) cell lines. Our data indicate that they could be considered for further evaluation as new anti-Alzheimer drug candidates.

ANTIOXIDANT AND PHYTOBIOLOGICAL STUDIES ON TWO ALLIUM CEPA L. EXTRACTS.

AIM: To investigate the antioxidant potential of two Allium cepa L. extracts. MATERIAL AND METHODS: The antioxidant activity of the two extracts (encoded EC1 and EC2) was assessed using two methods: DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging capacity and determination of their reducing power; phytobiological, studies were performed using grains of Triticum aestivum L., Falmura variety. RESULTS AND DISCUSSIONS: EC1 and EC2 extracts had a particular affinity for binding DPPH radicals. At equivalent concentrations, the reducing power of EClextract was about 2 times higher compared to EC2, increasing with the concentration of the analyzed sample. The phytobiological study demonstrated that the investigated extracts had no cytotoxic and genotoxic potential.

α,ß-DIBROMOCHALCONE DERIVATIVES--SYNTHESIS AND ANTIMICROBIAL ACTIVITY.

AIM: To obtain some chalcones and their dibrominated analogues and to evaluate their antimicrobial potential. MATERIAL AND METHODS: Eight chalcones were synthesized using the Claisen-Schmidt condensation of acetophenone/4-bromo-acetophenone and different benzaldehyde derivatives. These chalcones were further brominated using two different bromination agents: molecular bromine and pyridinium tribromide. The antimicrobial activity was tested using the disk diffusion method. RESULTS AND DISCUSSIONS: The classical bromination technique was compared to the eco-friendly one using pyridinium tribromide. Pyridinium tribromide bromination did not improve the reaction yields (except for one compound), but it had the advantage of being a stable, non-corrosive and non-toxic salt. The results of the antimicrobial assessment indicated that the bromination of the double bond slightly increased the antimicrobial potential in some cases, but the results obtained during the antimicrobial evaluation were modest, some of the derivatives being active especially on Sarcina lutea ATCC 9341 and Bacillus cereus ATCC 14579. CONCLUSIONS: In this study, eight chalcones and their dibrominated analogues were synthesized, four of the α,ß-dibromochalcones being reported for the first time. Pyridinium tribromide was used as an alternative for liquid bromine, the main advantage of this method being related to the reduced toxicity of the reagents. The synthesized compounds did not exhibit a very good antimicrobial potential.

Synthesis and in vitro analysis of novel dihydroxyacetophenone derivatives with antimicrobial and antitumor activities.

Herein we report a feasible study concerning the design, syntheses and in vitro antimicrobial and antitumoral activities of some novel compounds with dihydroxyacetophenone (DA) moiety. An efficient and general method for the preparation of diazine with dihydroxyacetophenone (DDA) skeleton under conventional thermal heating (TH), microwave (MW) and ultrasounds (US) irradiation is presented. Antimicrobial and antitumoral tests prove that some dihydroxyacetophenone compounds (the brominated derivatives BrDA 3) have a significant biological activity. It is also to be pointed out that, basically all the dihydroxyacetophenone derivatives proved to have a powerful antibacterial activity against drug resistant Gram-negative strain Pseudomonas aeruginosa ATCC 27853. Of particular interest could be the excellent antibacterial activity of our dihydroxyacetophenone compounds against drug resistant Gram-negative strain Pseudomonas aeruginosa.

Ultrasound and microwave assisted synthesis of dihydroxyacetophenone derivatives with or without 1,2-diazine skeleton.

A thorough study concerning O-alkylation and α-bromination of dihydroxyacetophenone (DA) and N-alkylation of 1,2-diazine, under ultrasound (US) and microwave (MW) irradiation as well as under conventional thermal heating (TH) is presented. Under US and MW irradiation the yields are higher, the amount of used solvent decreases substantially, the reaction time decreases considerable (from hours or days to minutes) and the consumed energy decreases, consequently the O-alkylation, α-bromination and N-alkylation methods could be considered environmentally friendly. A selective and efficient way to either bis-O-alkylation or mono-O-alkylation of DA has been found, the relative position of the two hydroxyl groups on the phenyl moiety being compulsory. A selective and efficient way for α-bromination in heterogeneous catalysis of DA derivatives under US irradiation is presented. The N-alkylation reaction of DA under US and MW irradiation proved to be the most convenient setup procedure for these types of reactions. Overall, the use of US proved to be more efficient than MW or TH.

[Antimicrobial activity of some cinnamic acid derivatives]. / Evaluarea actiunii antimicrobiene a unor derivati de acid cinamic.

Due to drug-resistance phenomenon, there is a constant need for discovering new antiinfectious agents. A series of cinnamic acid derivatives was synthesized and then brominated with bromine in the presence of chloroform or acetic acid. The structure of the new compounds was confirmed by elemental and spectral data. Their antimicrobial activity was tested by disc-diffusion method. The tested compounds had mainly antifungal activity and were moderately active against Gram-positive bacteria. Bromination of the double bond determined the enhancement of the antimicrobial activity for all the tested compounds.