Structural, vibrational, and electronic properties of the glucoalkaloid strictosidine: A combined experimental and theoretical study

A detailed structural analysis and spectral behavior of the glucoalkaloid strictosidine, a precursor of all monoterpene indole alkaloids, are discussed. The experimental NMR, FTIR, and UV results were compared to the theoretical DFT spectra calculated by Becke using the three-parameter Lee-Yang-Parr (B3LYP) function with 6-31G(d) and 6-311++G(2d,p) basis sets. The theoretical geometry optimization data were compared with the X-ray data for precursors and similar structures in the associated literature. The similarity between the theoretical and experimental coupling constants values made it possible to affirm the values of dihedral angles and their configuration, reinforcing findings from previous stereochemical studies. Theoretical UV analysis agreed well with the measured experimental data, with bands assigned. Calculated HOMO/LUMO gaps show low excitation energy for strictosidine, justifying its stability and reaction kinetics. The molecular electrostatic potential map shows opposite potentials regions that form hydrogen bonds that stabilize the dimeric form, which were confirmed by excellent agreement of the dimeric form theoretical wavenumbers with the experimental IR spectrum. ESI-MS/MS data revealed patterns for the fragmentation of the protonated strictosidine molecule outlined by an NBO study. © 2016 Renyer Alves Costa et al

Comparative docking of SARS-CoV-2 receptors antagonists from repurposing drugs

Observations: This work is not conclusive and is only computational simulations. Under no circumstances should we extrapolate in silico studies into clinical practice, as it would violate medical ethics principles. The main conclusion was that some drugs can be classified as false positives as predicted on the Hit Dexter 2.0 platform. Our main example is ivermectin, where the probability of nonspecificity is extremely high, thus leading to hasty and erroneous conclusions.SARS-CoV-2 is the seventh coronavirus to infect humans. Currently, there are no pharmacological treatments proven against COVID-19 or that may be of a broad spectrum to minimize the sequelae. This work aims to identify compounds or drugs already commercialized that may be supporting in the treatment of infectious conditions of COVID-19, parallel to the administration of vaccines. In this context, molecular docking simulations were carried out to understand which drugs are most effective in modulating a total of ten receptors, whether directly in viral, pro-inflammatory or central nervous system signaling, related to COVID-19. Subsequently, some results were validated through molecular dynamics simulations based on publicly available trajectory files. Among a total of 71 molecular docking simulations, the drug ledipasvir administered to patients with Hepatitis-C (HCV) was the most promising with a mean value ΔGº ≈ -10.3 kcal · mol-1 and a nonspecific probability according to neural networks of 0.21. Ivermectin, although it had an average affinity of -9.6 kcal · mol-1, was shown to be a ligand with a very expressive degree of nonspecificity of 0.93. When analyzing the atomic fluctuations of molecular dynamics, telaprevir stood out for the large number of rotational freedom in line with expressive RMSF fluctuations with a peak around 20 Å in the interaction with the Spike protein. Consequently, it was shown to be superior to the various anecdotally reported medications, such as nitazoxanide, and that due to the low mobility, the affinity was not so expressive due to the relative high fluctuations of 10 Å. Finally, these results seek to clarify from a theoretical point of view the interaction of numerous medications from viral signaling to the neuroinflammatory system.</div

Atividade biológica de extratos, hidrolatos e óleos voláteis de pau-rosa (Aniba duckei Kostermans) e quantificaç ão do linalol no hidrolato de folhas

The objective of this study was to evaluate the bioactivity of extracts and by-products of volatile oil extraction from rosewood, as well as to quantify linalool levels in hydrolates. Branch and trunkwood methanol extracts presented significant lethality to Artemia franciscana larvae (LC 50 58 ± 33 and 71 ± 31 mg mL -1, respectively). Hydrolates (diluted to 25%) and volatile oil (2 mg mL -1) caused 100% mortality. These results show that A. duckei is a potential source of cytotoxic substances. The volatile oil obtained from branchwood presented larvicidal activity in vitro towards Aedes aegypti (hemorrhagic dengue fever vector, LC 50 2,2 g L -1). Quantitative GC analysis performed on the hydrolate obtained from leaf extraction revealed a linalool concentration of 0.09% v/v (6 mM), which could be responsible for the observed bioactivity