Alicia Reyes-Arellano

Fluorescent property of 3-hydroxymethyl imidazo[1,2-a]pyridine and pyrimidine derivatives

BackgroundImidazo[1,2-a]pyridines and pyrimidines are important organic fluorophores which have been investigated as biomarkers and photochemical sensors. The effect on the luminescent property by substituents in the heterocycle and phenyl rings, have been studied as well. In this investigation, series of 3-hydroxymethyl imidazo[1,2-a]pyridines and pyrimidines were synthesized and evaluated in relation to fluorescence emission, based upon the hypothesis that the hydroxymethyl group may act as an enhancer of fluorescence intensity.ResultsCompounds of both series emitted light in organic solvents dilutions as well as in acidic and alkaline media. Quantitative fluorescence spectroscopy determined that both fused heterocycles fluoresced more intensely than the parent unsubstituted imidazo[1,2-a]azine fluorophore. In particular, 3-hydroxymethyl imidazo[1,2-a]pyridines fluoresced more intensely than 3-hydroxymethyl imidazo[1,2-a]pyrimidines, the latter emitting blue light at longer wavelengths, whereas the former emitted purple light.ConclusionIt was concluded that in most cases the hydroxymethyl moiety did act as an enhancer of the fluorescence intensity, however, a comparison made with the fluorescence emitted by 2-aryl imidazo[1,2-a]azines revealed that in some cases the hydroxymethyl substituent decreased the fluorescence intensity.

Imidazolines as Non-Classical Bioisosteres of N-Acyl Homoserine Lactones and Quorum Sensing Inhibitors

A series of selected 2-substituted imidazolines were synthesized in moderate to excellent yields by a modification of protocols reported in the literature. They were evaluated as potential non-classical bioisosteres of AHL with the aim of counteracting bacterial pathogenicity. Imidazolines 18a, 18e and 18f at various concentrations reduced the violacein production by Chromobacterium violaceum, suggesting an anti-quorum sensing profile against Gram-negative bacteria. Imidazoline 18b did not affect the production of violacein, but had a bacteriostatic effect at 100 μM and a bactericidal effect at 1 mM. Imidazoline 18a bearing a hexyl phenoxy moiety was the most active compound of the series, rendering a 72% inhibitory effect of quorum sensing at 100 μM. Imidazoline 18f bearing a phenyl nonamide substituent presented an inhibitory effect on quorum sensing at a very low concentration (1 nM), with a reduction percentage of 28%. This compound showed an irregular performance, decreasing inhibition at concentrations higher than 10 μM, until reaching 100 μM, at which concentration it increased the inhibitory effect with a 49% reduction percentage. When evaluated on Serratia marcescens, compound 18f inhibited the production of prodigiosin by 40% at 100 μM.

Targeting quorum sensing by designing azoline derivatives to inhibit the N-hexanoyl homoserine lactone-receptor CviR: Synthesis as well as biological and theoretical evaluations

To counteract bacterial resistance, we investigated the interruption of quorum sensing mediated by non-classical bioisosteres of the N-hexanoyl homoserine lactone with an azoline core. For this purpose, a set of selected 2-substituted azolines was synthesized, establishing the basis for a new protocol to synthesize 2-amino imidazolines. The synthesized compounds were evaluated as inhibitors of violacein production in Chromobacterium violaceum. Theoretical studies on bioisostere-protein interactions were performed using CviR. The results show that some azolines decreased violacein production, suggesting an antiquorum sensing profile against Gram-negative bacteria. Docking and molecular dynamic simulations together with binding free energy calculations revealed the exact binding and inhibitory profiles. These theoretical results show relationship with the in vitro activity of the azoline series.

Synthesis of Azolines and Imidazoles and their Use in Drug Design

Heterocycles are very important functional groups, especially in medicinal chemistry. They are not only pivotal in the synthesis of drugs, but also form part of the structure of a diversity of drugs, vitamins, natural products and biomolecules. The importance of azolines and imidazoles in heterocycles lies in the fact that their derivatives are known for analgesic, antifungal, antihypertensive, antiobesity, anticancer, and other biological activity. Additionally, they can inhibit butyrylcholinesterase, acetylcholinesterase, carboxylesterase and quorum sensing. Due to these properties, the present contribution reviews the use of azoline and imidazole moieties in recent drug synthesis based on classic as well as non-classic methods, the latter employing microwave and sonication energies. Also included is the preparation from oxazoline of nanostructured material having biomedical applications. Hence, the present focus is on the synthesis of azolines and imidazoles that are directly involved in the preparation of drug precursors and potential drugs.

Synthesis, molecular docking and biological evaluation of novel phthaloyl derivatives of 3-amino-3-aryl propionic acids as inhibitors of Trypanosoma cruzi trans-sialidase

In the last two decades, trans-sialidase of Trypanosoma cruzi (TcTS) has been an important pharmacological target for developing new anti-Chagas agents. In a continuous effort to discover new potential TcTS inhibitors, 3-amino-3-arylpropionic acid derivatives (series A) and novel phthaloyl derivatives (series B, C and D) were synthesized and molecular docking, TcTS enzyme inhibition and determination of trypanocidal activity were carried out. From four series obtained, compound D-11 had the highest binding affinity value (-11.1 kcal/mol) compared to reference DANA (-7.8 kcal/mol), a natural ligand for TS enzyme. Furthermore, the 3D and 2D interactions analysis of compound D-11 showed a hydrogen bond, π-π stacking, π-anion, hydrophobic and Van der Waals forces with all important amino acid residues (Arg35, Arg245, Arg314, Tyr119, Trp312, Tyr342, Glu230 and Asp59) on the active site of TcTS. Additionally, D-11 showed the highest TcTS enzyme inhibition (86.9% ± 5) by high-performance ion exchange chromatography (HPAEC). Finally, D-11 showed better trypanocidal activity than the reference drugs nifurtimox and benznidazole with an equal % lysis (63 ± 4 and 65 ± 2 at 10 μg/mL) and LC50 value (52.70 ± 2.70 μM and 46.19 ± 2.36 μM) on NINOA and INC-5 strains, respectively. Therefore, D-11 is a small-molecule with potent TcTS inhibition and a strong trypanocidal effect that could help in the development of new anti-Chagas agents.

A convenient electrolytic process for the reduction of aldehydes

We report an efficient electrolytic procedure for the reduction of aldehydes to primary alcohols in the absence of dimeric products. In this promising approach, based on environmentally friendly chemical synthetic methods, a simple electrolytic undivided cell was designed. Two copper plates served as electrodes and recycled water as the medium. A 6-V battery provided the required energy. Although initially the method was intended for the preparation of 2-aryl-3-hydroxymethyl imidazo[1,2-a]azines, it was successfully extended to reduce other aliphatic and aromatic aldehydes. The attractiveness of this procedure includes its operational simplicity, practical viability, inexpensiveness and good yields. In most cases the results were better than those obtained with the standard reduction procedure using sodium borohydride.

An abnormal C–H⋯O bond directs intermolecular bonding arrangements in bisimines

Abstract N,N-bis (3-nitrobenzylidene)ethylenediamine ( 1 ) formed a supramolecule with meso -hydrobenzoin, whereas N,N-bis (4-nitrobenzylidene)ethylenediamine ( 2 ) underwent a self-assembling process. The X-ray diffraction analysis showed that C–H⋯O intermolecular contacts play an important role in the building of both structures.

trans-Chlorido­(4-fluoro­benzene­thiol­ato-κS)bis­(tri­phenyl­phosphane-κP)palladium(II) methanol hemisolvate

The title compound, [Pd(SC6H4F-p)Cl(PPh3)2]·0.5CH3OH, features a PdII complex with two triphenylphosphane (PPh3) ligands arranged in a trans conformation, with one chloride and one 4-fluorobenzenethiolate ligand completing the coordination sphere, giving rise to a slightly distorted square-planar geometry of the PdII ion. The methanol solvent molecule is disordered about an inversion centre with an occupancy of 0.25 for each molecule. In the crystal, weak C—H⋯Cl hydrogen-bonding interactions between the complex molecules generate chain frameworks parallel to [010].

trans-Bis(μ-benzene­thiol­ato-κ2S:S)bis[chlorido­(tri­phenyl­phosphane-κP)palladium(II)] chloro­form disolvate

The title compound, [Pd2Cl2(C6H5S)2(C18H15P)2]·2CHCl3, contains a centrosymmetric dinuclear palladium complex with the PdII cation in a slightly distorted square-planar coordination environment. The PdII cations are bridged by the S atoms of two benzenethiolate ligands with different Pd—S distances [2.2970 (11) and 2.3676 (11) Å]. The coordination of the metal atom is completed by a chloride anion [2.3383 (11) Å] and a triphenylphosphane ligand [2.2787 (11) Å]. Weak C—H⋯Cl interactions are present between complex molecules and the CHCl3 solvent molecule. The latter is disordered over two positions in a 0.792 (8):0.208 (8) ratio. The crystal under investigation was found to be twinned by nonmerohedry, with a fraction of 73.4 (1)% for the major twin component.