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  • Open access
  • 16 Reads
Theoretical study on cation–π interaction in graphene fragments

The interaction between cations and delocalized electronic clouds (the cation-π interaction) occupies a very important place within non-binding interactions. Its presence has long been recognized as fundamental for both, the structure and function, of proteins and other important biological molecules. Rechargeable batteries and fuel cells industries of are also interested in cation-π interaction and the use of graphene and similar carbon allotropes are investigated as promising alternatives in their technological applications. Reliable and practically applicable theoretical models of cation-π interaction are needed for guiding these researches. In this work, the interaction of cations (Li+, Na+, K+, ammonium and guanidinium) with graphene fragments (from benzene to circumcoronene) is modeled using DFT level of theory. Linear scans (TPSS+D3/Def2TZVPP) that follow trajectories perpendicular to the central ring of the graphene fragments allow the location of the distance at which the strongest interaction takes place. Using the geometry of the minima, the interaction energy is decomposed in physically meaningful contributions using a SAPT(DFT) method (PBE0/Def2TZVP). It is observed that benzene complexes systematically deviate from the trend followed by complexes with larger fragments, so this system does not constitute a good model for the study of cation-π interaction in graphenes or other large conjugate molecules. While induction is the main contribution in complexes with Li+ and Na+, the stability of most of the complexes investigated depends on a balanced combination of the three contributions: electrostatic, induction and dispersion. Following the tendencies observed with organic fragments with an increasing number of conjugate rings, the results can be extrapolated to extended π systems as graphene.

  • Open access
  • 17 Reads
Antioxidant activity of biphenolic compounds anchored on mesoporous alumina

Phenolic antioxidants are used in the industry to delay the oxidation of fats being the most used butyl hydroxy anisole (BHA) and butyl hydroxy toluene (BHT). However, the consumer concern respects their safety has motived to study natural alternatives. In this sense, the aim of this work was to evaluate the behavior of 3,3'- dimethoxy-5,5'-di-2-propenyl-1,1'-biphenyl-2,2'-diol and 6,6'- dihidroxi-5,5’-dimethoxy-(1,1'-biphenyl)-3,3'-dicarbaldehyde free and supported on mesoporous alumina. Biphenolic compounds were synthesized by radical coupling and then anchored on alumina by microwave-assisted process. The antioxidant activity of these compounds was investigated by phosphomolybdenum method. The results showed that phenolic compounds anchored on mesoporous alumina have a marked antioxidant activity better than free antioxidants. Biphenolic compounds supported on alumina display antioxidant properties and hence have the potential for use as a food preservative, beverage, cosmetics, and pharmaceutical industries.

  • Open access
  • 13 Reads
New Tacrine derivatives and Tacrine-Chitosan systems for application against degenerative diseases

Chitosan is a natural non-toxic, biodegradable and biocompatible biopolymer, which is derived from chitin, whose structure allows a wide variety of chemical modifications that can confer new physical-chemical properties, functions and applications in different fields.

Among the great challenges facing the Society is the search for solutions to Alzheimer's disease. This disease presents high cellular oxidative stress, as a result of the imbalance between the oxidizing species generated in the cells and antioxidant compounds. One of the strategies used in the treatment of Alzheimer's is based on the use of acetylcholinesterase (AChE) inhibitors, an enzyme that catalyzes the hydrolysis of acetylcholine, a neurotransmitter involved in memory. In this context, Tacrine was the first drug approved for this purpose, later withdrawn due to liver damage caused by inducing oxidative stress.

Therefore, in the present work, new Tacrine derivatives that could reduce the original hepatotoxicity of the compound while preserving its properties as an AChE inhibitor have been prepared and characterized. Furthermore, by means of the formation of different functional bridges between Tacrine and Chitosan, new hybrid systems Tacrina-Chitosan, have been synthesized and characterized in order to serve as vectors of the drug in the human body. Among them, presence of a selenourea bridge must contribute to reduce oxidative stress, given the property of Se to reduce the number of ROS species in the cell.

  • Open access
  • 24 Reads
Green, microwave-assisted synthesis of O-perbutirylated-alkyl-glycosides

Carbohydrate chemical synthesis is a hard task that involves several protection and deprotection steps of hydroxyl groups to improve the regioselective formation of the glycosidic bond. Usually, this process is made through acylation reactions, where conventional heating and Lewis acids are used as promoters. However, these processes are time consuming, and sometimes catalysts disposal could represent an environmental problem. Given this, some alternatives to enhance the acylation process is the application of either microwaves and/or the use of other Lewis acids with less or null toxicity. Moreover, these approaches could be combined allowing to reduce reaction times and thus offering a “green” strategy synthesis for peracylated compounds. Thus, the present research proposes a green and fast alternative to produce peracylated glycosides through the synthesis of perbutyrilated sugars with potential to be used in enzymatic carbohydrate preparation. Model compound O-perbutirylated-phenyl-galactose was synthesized using imidazole as catalyst with different reaction conditions: at room temperature and assisted by microwaves. In the first case, reaction was held for 60 h, time required to totally consume the starting material according to TLC analysis. Then, modifications in perbutyrilation process and microwave assistance allowed to reduce to only 1 h for target sugar synthesis. NMR analyses confirmed that product formation was achieved with overall yields of 33% to reaction carried out at room temperature and 50% to microwave-assisted process. In conclusion, the combination of imidazole and microwaves is an excellent alternative to synthesize peracylated glycosides, which can be obtained swiftly and through a “green-chemistry” approach.

  • Open access
  • 41 Reads
A new efficient route to 2-alkylsemicarbazides

Synthesis of hardly available 2-alkylsemicarbazides and their hydrochlorides from semicarbazide hydrochloride has been developed. This general and efficient protocol is based on preparation of acetone semicarbazone, its N2-alkylation in the presence of sodium hydride, and hydrolysis under mild conditions.

  • Open access
  • 30 Reads
VALIDATED STABILITY- INDICATING HPTLC METHOD FOR NINTEDANIB & CHARACTERIZATION OF DEGRADANTS BY LC-MSn

A simple and rapid stability-indicating method for determination of nintedanib (NTB) in bulk drug using HPTLC and LC-MSn was developed and validated. Stress degradation studies were carried out by hydrolysis, oxidation, thermal and photolytic. Drug was found to be stable in thermal whereas one degradant was found in acid hydrolysis, three in basic hydrolysis, five in oxidative and two in photolytic stress. The probable structures of the degradation products were predicted & the degradation pathway was also established. Chromatography was carried out using silica gel 60 F254 TLC plate and mobile phase of Chloroform : Methanol in the ratio 7:3 v/v. The densitometric determination was done at 386 nm. The degradants were not detectable when stressed as per ICH recommended conditions but on increasing the strength of acid, base and peroxide, the degradants were very much prominent and were easily detectable in HPTLC. The LC system consisted of a Zorbax Bonus C18 (150 mm×4.6 mm, 3.5 µ). A gradient mobile phase consisting of mobile phase A: 10mM Ammonium formate (0.05% formic acid): ACN (pH 3.9) (90:10) and mobile phase B: 10mM Ammonium formate (0.05% formic acid): ACN (pH 3.9) (10:90) with a flow rate of 0.7mL/min was used to separate the degradants up to a total retention time of 15 min. Mass spectrometric detection was performed using Thermo Scientific LCQ fleet Ion Trap LC/MSn.

  • Open access
  • 35 Reads
Activiral activity and physicochemical properties of 4-Amino-phenyl-quinazoline derivatives for Bovine Viral Diarrhea Virus (BVDV).

Bovine viral diarrhea virus (BVDV) is a pestivirus whose infection in cattle is globally distributed being endemic in many countries. The use of antivirals could complement vaccination as a tool of control and reduce economic losses.

We have identified potential molecules that dock into the allosteric binding pocket of BVDV RdRp via structure-based virtual screening approach. Five of these compounds resulted active against BVDV in vitro and displayed EC50 values in the sub and low-micromolar range. One of them, N-(2-morpholinoethyl)-2-phenylquinazolin-4-amine (EC50= 9.68 ± 0.49 µM), was selected to perform different chemical modifications in order to improve its antiviral profile. Thirty-nine derivatives were obtained, seven of which showed improved antiviral activity. Between them, 2-(4-(2-phenylquinazolin-4-yl)piperazin-1-yl)ethanol afforded the best values of antiviral activity and selectivity index (SI) and their physicochemical properties was examined in vitro, in terms of solubility and stability.

The solubility (S) of the last compound was evaluated at pH 1.2, 6.8, and 7.4, employing the shake flask method by UV spectroscopy, while the stability was tested in mouse plasma by HPLC. The compound presented good solubility values at pH 1.2, 6.8 and 7.4, which were in concordance within the range normally observed for oral drugs, i.e., 4-4000 µg/mL (corresponding to S values ranging from 10-2 to 10-5 M for molecules with a molecular weight of 400). Stability studies in mouse plasma showed that the compound is stable at least for 120 min.

  • Open access
  • 102 Reads
A MOLECULAR DOCKING OF NEW 9β-HALOGENATED PROSTAGLANDINE ANALOGUES

Prostaglandins with cytoprotective activity were studied for a long time and a few PGE1 and PGE2 stable analogues were promoted as drugs: arbaprostil, enprostil, misoprostol and rioptostol; the same activity has nocloprost, a 9β-chlorine prostaglandin analogue, and many 9β- ar 11β-substituted prostaglandins were synthesized and studied for their biological activity. We previously synthesized new 9β-halogenated prostaglandins with an ester group at the carbon atom 6 (PGs numbering) by reaction of a δ-lactone intermediate with diols in acid catalysis.

These compounds were now used in a molecular docking study to determine their potential cytoprotective (anti-ulcer) activity. The study has been done with CLC Drug Discovery Workbench 2.4. software and an oxidoreductase enzyme receptor, chosen from the Protein Data Bank, ID: 4KEW. (www.rcsb.org). In the study we used as standard two recognized drugs, omeprazole (co-crystallized with the enzyme) and nocloprost. The 9β-halogenated prostaglandin analogs were finally docked. Nocloprost and all 9β-halogenated compounds had docking score greater than that of omeprazole. The majority of the 9β-halogenated analogs have a docking score even greater than that of nocloprost, indicating that these compounds could have potential cytoprotective (anti-ulcer) activity. A few correlations between docking score and substituents on the prostaglandin skeleton have been done.

  • Open access
  • 36 Reads
AURONE AS PROMISING HUMAN PANCREATIC LIPASE INHIBITORS THROUGH IN SILICO STUDY

In this study, 82 aurone compounds, a subclass of flavonoids were investigated towards to human pancreatic lipase inhibitory activity. Molecular docking of the aurones was done successfully into the catalytic position of lipase (Pdb: 1LPB) using AutoDock Vina software 1.5.7.rc1. The results showed that 62 compounds interacted well with residues in the catalytic trial Ser152-Asp176-His263 and Phe77 of protein 1LPB. In particular, A32 was selected as the best binding compound (docking score: -10.6 kcal.mol-1) and suitable for oral drug following the 5-Lipinski rule. Combining the results of docking and molecular dynamics simulation of A32- protein complex during 10 ns, this study performed that the A32 compound bound well and formed a stable complex with 1LPB protein. Therefore, the A32 compound was considered as the lead compound which could be synthesized and tested for pancreatic lipase inhibitor.

  • Open access
  • 15 Reads
Highly asymmetric reduction of new benzofuryl and benzothiophenyl α-amino ketones

Heterocyclic compounds play an important role in the medicinal chemistry and occupy a central position in synthetic organic chemistry. Both benzofuran and benzothiophene are considered as very important structures due to their diverse biological and pharmacological profile. Many of the clinically approved drugs are synthetic and naturally occurring substituted benzofuryl and benzothiophenyl derivatives in conjunction with other heterocycles. Therefore a new series of α-amino ketones (containing various azole rings) derivatives of benzofuran and benzothiophene were synthesized and subjected to the transfer hydrogenation with formic acid, catalyzed by RhCl[(R,R)-TsDPEN](C5Me5). The corresponding optically active β-amino alcohols were obtained in high yields and excellent enantioselectivities (93-99%), as determined by chiral HPLC. The absolute configuration of the products was confirmed by means of ECD spectroscopy supported by theoretical calculations.

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