The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly impacted human lives, overburdened the healthcare system and weakened global economies. The lack of specific drugs against SARS-CoV-2 is a significant hurdle towards the successful treatment of COVID-19. The SARS-CoV-2 Main protease (M^pro) is considered an appealing target because of its role in replication in host cells. Plant-derived natural compounds are being largely tested for their efficacy against COVID-19 targets to combat SARS-CoV-2 infection. To discover hit compounds that can be used alone or in combination with repositioned drugs, we curated a set of 2,24,205 natural product structures from the ZINC database and virtually screened against covid-19 M^pro. The sequential docking protocols involving different level of exhaustiveness were performed to screen a library of natural compounds. Final 88 compounds were selected and post-processed using the MM-GBSA analysis for the generation of binding free energies. The top four compounds (ZINC000085626103, ZINC000085569275, ZINC000085625768 and ZINC000085488571) showing higher affinity against covid-19 M^pro enzyme selected for MD simulation studies. The RMSD, RMSF and RoG analysis of the all four compound-protein complexes indicated the absolute stability during 100ns MD run. Further the post-MD simulation binding free energies were calculated for all four compounds and were found to be in range of -38.29 to -18.07 kcal/mol. The In-silico virtual screening results suggested that the selected natural compounds have the potential to be developed as a COVID-19 M^pro inhibitor and can be explored further for experimental research to evaluate the in vitro and in vivo efficacy of these compounds for the treatment of COVID-19.

The aim of this research is to identify potential candidate molecules against Leishmania mexicana, a local pathogen causative of leishmaniasis. Leishmaniasis is a neglected tropical disease that poses a significant public health challenge in the Americas due to its high incidence, morbidity, widespread geographic presence, diverse parasite species, various clinical manifestations, and the absence of adequate therapeutic and preventative measures. L. mexicana is the causative agent of cutaneous leishmaniasis in Mexico and Central America. Ecuador is an endemic area for cutaneous leishmaniasis with around 1200 annual cases. Many of the drugs used to treat leishmaniasis are from the early and mid-20th centuries, have limited efficacy in advanced stages of the disease, are nonspecific, and/or are highly toxic. Finding new starting points for developing new drugs to effectively treat and control these diseases is therefore a priority.

The current increase in microbial resistance is a very serious public health problem that requires immediate attention from the scientific-multidisciplinary sector and is supported by the corresponding socio-political commitment. Here we screen, through in silico methods, pre-synthesized compounds provided by Medicines for Malaria Venture (MMV) in the Pandemic Response box (PRB) (www.mmv.org). PRB is a collection of 400 compounds to facilitate drug discovery (Samby et al., 2022). The collection contains chemically characterized compounds that are freely available to the scientific community, with the understanding that the data will be shared. Here we assess the antimicrobial potential of the novel compounds against topoisomerases type II of L. mexicana by molecular docking. This pathogen has one Topo II located in the nucleus and another located in the mitochondria. These enzymes are essential for the parasite´s survival. We identified the 20 best candidates for both enzymes being 5 of the themes shared by both targets. These promising antimicrobial molecules will be tested in vitro against eukaryotic macrophages and leishmania models (promastigotes and amastigotes), to validate their effectivity.

Introduction

Recently, we have synthesized 2-(ethoxymethylene)malononitrile 1 to reveal its crystal structure. This simply built compound is a very convenient building block for the construction of various heterocycles and it is assuming as an intermediate in different three-component reactions. In this study, we present the results of XRD of the titled compound demonstrating in crystal the linkage of the co-oriented molecules via N-H···N≡C non-covalent interactions. To evaluate the energy of such interactions, we conducted DFT simulations.

Experimental

The ¹H and ¹³C NMR spectra were recorded with a Varian (Agilent) 400 spectrometer. An XRD study of 1 was performed an Xcalibur Ruby diffractometer. Compound 1 was obtained by the known procedure. Coordinates from Xray data were used as initial and full geometry optimization of monomers and dimers were performed using DFT with different functionals and the 6-311++G(d,p) basis set.

Results and Discussion

The molecules of 1 are linked into infinite chains via N-H···N≡C close contacts with distance of 2.494(3) Å. When theoretical measuring the energy of H···N non-covalent interactions by DFT, it was determined by M06-2X functional equal to -1.20 kcal/mol meaning weak attraction.

Acknowledgments

This work was supported by the Russian Science Foundation (grant no. 22-23-00171 to VSG).

Introduction

n,n'-(Alkanediyl)-bis(2-phenyl-3,5-dihydro-4H-imidazol-4-one)s (1) are of interest not only from the point of view of their chemical structure, but due to the properties of their N-alkylated derivatives. The latter are a class of biogenic QACs, which have antiseptic and disinfectant properties that have become especially relevant over the past few years. In this study, we investigated the conformational abilities of the titled compounds to gain insight into their biological potential as a platform for the generation of various QACs.

Experimental

The ¹H and ¹³C NMR spectra were recorded with a Varian (Agilent) 400 spectrometer. Quantum chemical calculations were performed using DFT at the B3LYP/6-31G(d,p) theory. Conformational analysis of the synthesized compounds was carried out using the Frog2 program followed by the optimization by the MM method AMMOS.

Results and Discussion

Among the conformers of 1, due to the flexibility of the polymethylene fragment, the phenyl rings can take on different mutual arrangements, while there is a clear tendency for the formation of π-π interactions of the rings. From the point of view of reactivity towards alkylating agents, a preliminary conclusion can be drawn about the favorable mutual arrangement of imidazolone rings, located at a sufficient distance to carry out both mono- and bisalkylation to obtain bis-QAC.

In this study, a rapid, simple approach was applied for the synthesis of silver nanoparticles using Pistia stratiotes aqueous leaf extract. The plant extract acts both as a reducing agent and as a capping agent. To identify the compounds responsible for the reduction of silver salt, the functional groups present in plant extract were investigated by FTIR (Fourier-Transform Infrared Spectroscopy). Various techniques used to characterize synthesized nanoparticles are surface morphology and particle size analysis by TEM (Transmission Electron Microscopy) and UV- visible spectrophotometer showed an absorbance peak in the range of 422 nm, surface morphology analyzed by SEM (Scanning Electron Microscopy), elemental analyzed by EDX
(Energy-dispersive X-ray spectroscopy), and Crystallinity analyzed by XRD (X-ray Powder Diffraction). The silver nanoparticles showed antibacterial activities against gram-negative (Escherichia coli) microorganisms. Results confirmed this protocol as simple, rapid, one-step, eco-friendly, non-toxic, and an alternative to conventional physical/chemical methods. Only 30 min were required for the conversion of silver salt into silver nanoparticles at room temperature, without the involvement of any hazardous chemical.

Abstract

In the context of the study of neurodegenerative diseases, particularly Alzheimer's disease (AD), this work focuses on the synthesis of tetrahydroquinolines (THQ) using a previously reported method, with N-allyl and N-propargyl structural variants. The antioxidant activity was evaluated through ABTS and DPPH assays, contributing to the calculation of SC₅₀ (free radical scavenging) through dose-response curves. Similarly, the enzymatic inhibition of AChE (acetyl cholinesterase) and BChE (butyryl cholinesterase) was determined to obtain the IC₅₀ values, framed within the cholinergic hypothesis for AD treatment.

A toxicity analysis was carried out through the in vitro hemolysis assay, demonstrating low toxicity of the evaluated compounds. Additionally, in silico ADME analysis (Swiss ADME tool) predicted a high probability of penetration through the blood-brain barrier (BBB), along with the estimation of relevant parameters regarding their biotransformation and involvement in xenobiotic metabolism.

It is important to highlight that the N-allyl/propargyl-THQs with a methyl substituent showed the highest activity in the different assays, where N-allyl exhibited better efficiency in inhibiting BChE and N-propargyl in AChE. Furthermore, ABTS seems to be more suitable than DPPH for THQ compounds, as DPPH showed low reactivity overall. These findings represent a significant advancement in the development of compounds with potential palliative therapeutic effects for AD, proposing THQs as promising candidates. The future research projection aims to elucidate mechanisms of action and complement with various bioactivity and cytotoxicity assays.

Introduction

Dimethylaminomethylenefuran-2(3Н)-ones are highly reactive due to the presence of several active reaction centers, as well as the pronounced push-pull nature of the C=C bond, which makes it possible to modify them in several directions.

Experimental details

The synthesis of 5-aryl-3-((dimethylamino)methylene)furan-2(3H)-ones was carried out by reacting 5-arylfuran-2(3H)-ones with dimethylformamide dimethyl acetal in equimolar quantities using solvents of different polarities. The structure of the obtained products was established using spectroscopic methods.

Results and Discussion

The introduction of a dimethylaminomethylene fragment into the molecule of 5-arylfuran-2(3H)-ones was achieved using a Monowave50 closed-type reactor. Based on NOESY1D NMR spectroscopy, it was established that the final structures exist as the E-isomer.

The unique size- and shape-dependent optical and thermal properties of gold nanoparticles (AuNPs), as well as versatility of their functionalization and targeting, make them valuable tools in a variety of scientific and technological fields for a wide range of applications, including diagnostics, drug delivery, imaging, sensors development, and synthesis of organic compounds [1-3].

Among AuNPs, gold nanorods (AuNRs) are in high demand due to the tunability and sensitivity of their longitudinal surface plasmon resonance [4, 5]. The anisotropic AuNRs structure displays two surface plasmon bands, corresponding to surface electron oscillation on transverse and longitudinal sides [6]. Typically, a two-step synthesis process using surfactants and seed particles, where gold seeds are prepared and then added to the growth solution, is used. Researchers continue to explore new applications for these nanomaterials, making them an active area of research and development [7].

The main aim of this study was to synthesize AuNRs of different lengths using different methods. The obtained AuNRs were characterized using the techniques SEM, DLS, and UV-VIS. These techniques allowed a detailed study of the structural and optical properties of the AuNRs and provided valuable insight into the synthesis. The characterization results were crucial to guide the synthesis and to further understand the potential applications of AuNRs.

In the broader realm of polymers, while they find numerous applications, conducting polymers (CPs) hold immense promise for the future, particularly in the context of their use across a wide spectrum of technological applications in various fields [1]. The ability of some polymers to conduct electric current has led to the term "conducting polymers. There are natural, synthetic, and semi-synthetic polymers: conducting polymers are synthetic “metallic” polymers [2].The synthesis of CPs can be carried out using chemical, electrochemical, enzymatical, and other methods. Commonly encountered CPs encompass polyaniline (PANI) and polypyrrole (PPy). PPy, in particular, stands out due to its remarkable characteristics, including its ease of synthesis, adaptability in structure, lack of toxicity, exceptional electrical conductivity, and strong redox capabilities. On the other hand, PANI boasts advantages such as straightforward synthesis, impressive stability in varying environmental conditions, favorable electrical conductivity (of the p-type), and affordability [3].

In this study, we have chosen various synthesis approaches for producing nanomaterials of PANI and PPy, and subsequently carried out the synthesis procedures. Additionally, the obtained materials are investigated by scanning electron microscopy (SEM), UV-VIS spectroscopy, dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FTIR). Obtained results allow to control synthesis of PPy and PANI nanostructures.

Bioisosteres of amide bonds such as 1,5-disubstituted-1,2,3-triazoles (1,5-DS-1,2,3-Ts) and 1,5-disubstituted tetrazoles (1,5-DST) are present in compounds with important biological activities like antineoplastic, antibacterial, antifungal and antiparasitic; and antifungal, antiparasitic, antiviral, and anti-inflammatory, respectively. In the present work, we present the synthesis of tetrazole-triazole bis-heterocycles via Ugi-Azide strategy. Bis-heterocycles were synthesized with moderate yields, under mild conditions, employing 2H-1,2,3-triazole aldehyde.