Design, in silico studies, synthesis and in vitro evaluation of oseltamivir derivatives as inhibitors of neuraminidase from influenza A virus H1N1.

Since the neuraminidase (NA) enzyme of the influenza A virus plays a key role in the process of release of new viral particles from a host cell, it is often a target for new drug design. The emergence of NA mutations, such as H275Y, has led to great resistance against neuraminidase inhibitors, including oseltamivir and zanamivir. Hence, we herein designed a set of derivatives by modifying the amine and/or carboxylic groups of oseltamivir.

Design of multi-target compounds as AChE, BACE1, and amyloid-β(1-42) oligomerization inhibitors: in silico and in vitro studies.

Despite great efforts to develop new therapeutic strategies against Alzheimer's disease (AD), the acetylcholinesterase inhibitors (AChEIs): donepezil, rivastigmine, and galantamine, have been used only as a palliative therapeutic approach. However, the pathogenesis of AD includes several factors such as cholinergic hypothesis, amyloid-β (Aβ) aggregation, and oxidative stress. For this reason, the design of compounds that target the genesis and progression of AD could offer a therapeutic benefit.

Three amino acid derivatives of valproic acid: design, synthesis, theoretical and experimental evaluation as anticancer agents.

Valproic acid (VPA) is extensively used as an anticonvulsive agent and as a treatment for other neurological disorders. It has been shown that VPA exerts an anti-proliferative effect on several types of cancer cells by inhibiting the activity of histone deacetylases (HDACs), which are involved in replication and differentiation processes. However, VPA has some disadvantages, among which are poor water solubility and hepatotoxicity.

Ethers and esters derived from apocynin avoid the interaction between p47phox and p22phox subunits of NADPH oxidase: evaluation in vitro and in silico.

NOX (NADPH oxidase) plays an important role during several pathologies because it produces the superoxide anion (O2•-), which reacts with NO (nitric oxide), diminishing its vasodilator effect. Although different isoforms of NOX are expressed in ECs (endothelial cells) of blood vessels, the NOX2 isoform has been considered the principal therapeutic target for vascular diseases because it can be up-regulated by inhibiting the interaction between its p47phox (cytosolic protein) and p22phox (transmembrane protein) subunits. In this research, two ethers, 4-(4-acetyl-2-methoxy-phenoxy)-acetic acid (1) and 4-(4-acetyl-2-methoxy-phenoxy)-butyric acid (2) and two esters, pentanedioic acid mono-(4-acetyl-2-methoxy-phenyl) ester (3) and heptanedioic acid mono-(4-acetyl-2-methoxy-phenyl) ester (4), which are apocynin derivatives were designed, synthesized and evaluated as NOX inhibitors by quantifying O2•- production using EPR (electron paramagnetic resonance) measurements.

o-Alkylselenenylated benzoic acid accesses several sites in serum albumin according to fluorescence studies, Raman spectroscopy and theoretical simulations.

In the circulatory system, serum albumin (SA) is an important transporter of the majority of molecules with biological activity. We focused the current study on the anti-inflammatory compound, o-alkylselenenylated benzoic acid (ALKSEBEA), to determine its ability to access SA. Herein, we employed experimental procedures (fluorescence studies, Raman spectroscopy) and docking study on SA obtained from the Protein Data Bank and key conformers obtained from molecular dynamics simulations.

Synthesis and anti-inflammatory activity evaluation of unsymmetrical selenides.

The alkylation reaction of 2,2'-diseleno and 4,4'-diseleno-bis(benzoic acid) derivatives in the presence of sodium borohydride and alkyl halides allowed the synthesis of various new o- and p-alkylselenenylated benzoic acid derivatives in good yields. The anti-inflammatory activity of selected selenide derivatives on granuloma induced by subcutaneous implantation of cotton pellets in Wistar rats was examined. Selenium derivatives 2a, 2c and 2e showed anti-inflammatory activity although to a lesser extent as compared to indomethacin, however they were found less toxic than the latter.

Crystal structure of 2-selenobenzyl-1-benzoic acid.

C14H12O2Se is monoclinic, P2(1)/c. Unit-cell dimensions at 293 K are a = 8.1055(7), b = 5.

Crystal structure of 2-Se-(2-methyl-2-propenyl)-1-benzoic acid.

C11H12O2Se is triclinic, P1. Unit-cell dimensions at 293 K are a = 5.8450(10), b = 8.

Crystal structure of dibenzoyl diselenide.

C14H10O2Se2 is monoclinic, P2(1)/c. The unit-cell dimensions at 293 K are a = 12.795(2), b = 12.