Effect of ß - hydroxy - γ -aminophosphonate (ß - HPC) on the hydrolytic activity of Nocardia brasiliensis as determined by FT-IR spectrometry.

The use of immunomodulatory and metabolic modulating drugs has been considered a better strategy to improve the efficacy of conventional treatments against pathogens and metabolic diseases. L-carnitine is relevant in fatty acid metabolism and energy production by ß-oxidation, but it also has a beneficial therapeutic immunomodulatory effect. The ß-hydroxy-γ-aminophosphonate (ß-HPC) was developed, synthesized and studied in different pathologies as a more soluble and stable analog than L-carnitine, which has been studied in bacterial physiology and metabolism; therefore, we set out to investigate the direct effect of ß-HPC on the metabolism of N. brasiliensis, which causes actinomycetoma in Mexico and is underdiagnosed. To analyze the effect of ß-HPC on the metabolic capacity of the bacterium for the hydrolysis of substrate casein, L-tyrosine, egg yolk, and tween 80, Fourier transform infrared spectroscopy (FT-IR) was employed. It was found that ß-HPC increases the metabolic activity of N. brasiliensis associated with increased growth and increased hydrolysis of the substrates tested. By the effect of ß-HPC, it was observed that, in the hydrolysis of L-tyrosine, the aromatic ring and functional groups were degraded. At 1515 cm-1, any distinctive signal or peak for this amino acid was missing, almost disappearing at 839, 720, 647, and 550 cm-1. In casein, hydrolysis is enhanced in the substrate, which is evident by the presence of NH, OH, amide, and CO. In casein, hydrolysis is enhanced in the substrate, which is evident by the presence of NH, OH, amide, COO, and P = O signals, characteristic of amino acids, in addition to the increase of the amide I and II bands. In Tween 80 the H-C = and C = C signals disappear and the ether signals are concentrated, it was distinguished by the intense band at 1100 cm-1. Egg yolk showed a large accumulation of phosphate groups at 1071 cm-1, where phosvitin is located. FT-IR has served to demonstrate that ß-HPC is a hydrolysis enhancer. Furthermore, by obtaining the spectrum of N. brasiliensis, we intend to use it as a quick comparison tool with other spectra related to actinobacteria. Eventually, FT-IR may serve as a species identification option.

Evaluation of Inhibitory Activity In Silico of In-House Thiomorpholine Compounds between the ACE2 Receptor and S1 Subunit of SARS-CoV-2 Spike.

At the end of 2019, the world was struck by the COVID-19 pandemic, which resulted in dire repercussions of unimaginable proportions. From the beginning, the international scientific community employed several strategies to tackle the spread of this disease. Most notably, these consisted of the development of a COVID-19 vaccine and the discovery of antiviral agents through the repositioning of already known drugs with methods such as de novo design. Previously, methylthiomorphic compounds, designed by our group as antihypertensive agents, have been shown to display an affinity with the ACE2 (angiotensin converting enzyme) receptor, a key mechanism required for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) entry into target cells. Therefore, the objective of this work consists of evaluating, in silico, the inhibitory activity of these compounds between the ACE2 receptor and the S1 subunit of the SARS-CoV-2 spike protein. Supported by the advances of different research groups on the structure of the coronavirus spike and the interaction of the latter with its receptor, ACE2, we carried out a computational study that examined the effect of in-house designed compounds on the inhibition of said interaction. Our results indicate that the polyphenol LQM322 is one of the candidates that should be considered as a possible anti-COVID-19 agent.

Structure-Activity Relationship (SAR) and in vitro Predictions of Mutagenic and Carcinogenic Activities of Ixodicidal Ethyl-Carbamates.

Ethyl-4-bromophenyl-carbamate (LQM 919) and Ethyl-4-chlorophenyl-carbamate (LQM 996) are compounds that inhibit egg-laying and hatching of tick larvae that are resistant to conventional ixodicides. The structure-activity relationship (SAR) to get the endpoint predictions of mutagenicity and carcinogenicity of the LQM 919 and LQM 996 was performed and the absence of mutagenicity was confirmed by Ames test. SAR analysis show no structural alerts indicating the ability of ethyl-carbamates to bind biomolecules or estrogen receptors. Endpoint of mutagenicity with and without metabolic activation showed that the ethyl-carbamates were negative (p <0.05) for mutagenicity induction in strains TA97, TA98, TA102, TA1535, TA1537 and TA1538 of Salmonella typhimurium. Pre-incubation with different ethyl-carbamate concentrations did not increase the number of spontaneously reverting colonies; moreover, the compounds did not induce a concentration-dependent increase in the number of reverting colonies in any of the strains used. This confirmed the absence of mutagenic activity in this test system. Exogenous metabolic activation did not modify these observations; suggesting that no metabolites with mutagenic activity were present. The endpoint of carcinogenicity in rats were negative for LQM 919 (p <0.05,) and LQM 996 (p <0.001). The results of the present study strongly suggest that ethyl-carbamates do not represent a risk for cancer in mammals.

Docking Studies of Methylthiomorpholin Phenols (LQM300 Series) with Angiotensin-Converting Enzyme (ACE).

A main target in the treatment of hypertension is the angiotensin-converting enzyme (ACE). This enzyme is responsible for producing angiotensin II, a potent vasoconstrictor. Therefore, one of the targets in the treatment of hypertension is to inhibit ACE activity. Hence, this study's aim is to use computational studies to demonstrate that the proposed heterocyclic compounds have a molecular affinity for ACE and that, furthermore, these heterocyclic compounds are capable of inhibiting ACE activity, thus avoiding the production of the vasopressor Angiotensin II. All this using computer-aided drug design, and studying the systems, with the proposed compounds, through molecular recognition process and compared with the compounds already on the market for hypertension.