Introduction: SARS-CoV-2 is an emerging pathogen that has strongly affected humanity over the past few years. Its S-glycoprotein receptor-binding domain provides the primary recognition of the host cell and initiates the viral penetration.The goal of our work was to find potential inhibitors of the entry stage of the SARS-CoV-2 life cycle. Methodology: firstly seven investigated compounds were prepared by generating their three-dimensional coordinates and protonating according to neutral pH in the OpenBabel ObGUI interface. Next, the mini-library was docked into the RBD interaction site with hACE2 using the AutoDock Vina. Part of the target amino acid residues was considered mobile. Based on the affinity assessment, four substances were selected for research in a simulation experiment implemented within the CHARMM-GUI, GROMACS and gmx_MMPBSA functionality. Results: only four out of seven studied compounds were characterized by the optimal initial pattern of interactions and the calculated affinity. Further simulation studies allowed to discard three more on the basis of their dissociation from the docking site within 5ns from the simulation beginning. The last compound pyrazolothiadiazepine 1794 had an optimal position and the RMSD value of 1-2 Å during 150ns of simulation. At the same time, the calculated binding free energy of 1794 with RBD was -20.59 kcal/mol. Conclusion: on the basis of molecular dynamics simulation analysis of the ligand-receptor complex, compound 1794 was selected as a potential inhibitor of the SARS-CoV-2 RBD interaction with human ACE2. It is characterized by the RMSD within 1-2 Å and a calculated ΔG of -20.59 kKal/mol.

Apart from the pharmacodynamics of drugs and the resistance of the Plasmodium falciparum parasite to existing antimalarial drugs, pharmacokinetic-related properties of drugs also hamper their translation. The need to develop novel drugs with optimum solubility profiles necessitated the training of an efficient machine learning regression model for the prediction of the solubility of a series of compounds. Four descriptors: octanol-water partition coefficient, molecular weight, number of rotatable bonds and aromatic proportion from the simplified molecular-input line-entry system (SMILES) of 11,478 antiplasmodial molecules were used. This was trained using five regression models; multiple linear regression, k-nearest neighbors, LASSO regression, support vector regressor and random forest regressor (RFR)) to predict the solubility of molecules. The evaluation metrics (R², mean squared error (MSE), mean absolute error (MAE) and root mean squared error (RMSE)) were used to assess the model performance. Of the performed algorithms, the RFR produced a robust model with model statistics of MSE 0.54, R² 0.85, MAE 0.41 and RMSE 0.73. The F-statistic for the model was 7214, showing a strong correlation between the descriptors and solubility of molecules. This could efficiently predict the antimalarial activity for untested molecules to select promising ligands as leads for further optimization.

The goal is to develop a throat spray containing Bacillus and ivy leaves extract that prevents and aids in the treatment of pharyngitis and upper respiratory tract infections. JMP 14 Pro software was used to create an experimental model using 16 formulas. The percentages of ivy leaves extract, honey, and Bacillus spores are independent variables, while Bacillus survival and mean beam width spray are dependent variables. Based on the variance analysis of the dependent variables and the effect of the independent factors on the dependent variable, the computer creates optimum equations with various desired values. The assessment of appropriate formulae by examining anti-inflammatory efficacy as well as quality standards such as organoleptic, pH, qualitative ivy leaves extract, and Bacillus survival quantification. The findings demonstrated that JMP 14 Pro suggested an ideal formula with an index that was the most preferred and contained 1,65% ivy leaves extract. The survey approach showed that the formula had good anti-inflammatory power when compared to the reference drug. The anti-inflammatory potential was evaluated using the mouse paw edema test on white mice. The end product is a suspension with a mild and sweet flavor. It achieves a constant spray volume, with a pH range of 5,5 to 6,5, and a round or almost circular spray shape that measures 7,2 to 9,3 cm in diameter. It also matches the standard's Rf on thin layer chromatography (HPTLC). Strong anti-inflammatory properties are present in the optimal formulation of the Bacillus-containing throat spray, and the quality criteria are studied as a basis for the eventual establishing of the product's quality standards.

A series of novel 4-benzyl-morpholine-2-carboxylic acid N0-[2-(4-benzoyl-phenoxy)-acetyl]-hydrazide derivatives 8a-j has been synthesized from (4-hydroxy-aryl)-aryl methanones through a multi-step reaction sequence and then evaluated for anti-proliferative activity in vitro against various types of neoplastic cells of mouse and human such as DLA, EAC, MCF-7 and A549 cells. From the cytotoxic studies and structural activity relationship of compounds 8a-j, it is clear that methyl group on the B ring of benzophenone is essential for antiproliferative activity and bromo at ortho position (compound 8b) and methyl at para position (compound 8f) on A ring of benzophenone are significant for extensive anti-mitogenic activity. Investigation on clonogenesis and Fluorescence-activated cell sorting suggests that compounds 8b and 8f have the potency to exhibit the prolonged activity with cell cycle arrest on G2/M phase against cancer progression. Further, the compounds 8b and 8f inhibit murine ascites lymphoma through caspase activated DNase mediated apoptosis.

Wild Syrian rue (Peganum harmala L. family Zygophyllaceae) is wellknown in North Africa. It is widely used in traditional medicine. Recent years of research has demonstrated different pharmacological and therapeutic effects of P. harmala and its active alkaloids. This research aims to examine the antioxidant properties of alkaloids extracted from Peganum harmala seeds. Alkaloids were extracted using the organic solvent extraction method to obtain a total alkaloid extract. The extraction of alkaloids from Peganum harmala seeds gave a high yield of 3.49%. Antioxidant activity was assessed by two tests: DPPH (2, 2 diphényl 1 picrylhydrazyl) and FRAP (Ferric reducing antioxidant power). The evaluation of the DPPH• free radical scavenging power showed that the inhibitory concentrations expressed in IC50 obtained was 118.96 µg/ml. In addition, the FRAP method indicated that alkaloid extract from Peganum harmala seeds possess a good iron reducing power compared with standard antioxidant (ascorbic acid). These results suggest that alkaloids of Peganum harmala seeds have the potential to be exploited as a new food product and are a reservoir of bioactive molecules with prospective applications as ingredients for value-added, functional, and/or preservative food products.

Introduction:

Cancer remains a significant global health concern, necessitating the exploration of novel anti-cancer treatments. Extensive research supports the potential of using plant extracts and silver nanoparticles (AgNPs) as a safer and more effective alternative treatment for cancer patients. Our study specifically investigates the antibacterial and anticancer properties of silver nanoparticles and bio-components from Rhazya Stricta (R.S.) extract, synthesized using silver nitrate (AgNO3). By exploring this treatment option, we aim to provide a safer and more effective alternative to chemotherapy, which can cause severe side effects and increased infection risks for patients.

Method:

AgNPs were synthesized using an aqueous extract of R.S. aerial parts. The organic components were detected using Fourier Transform Infrared (FTIR) spectroscopy, while size distribution, morphology, and surface analysis were examined using Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM) with Energy Dispersive X-ray (EDX) analysis, and Zetasizer measurements. The cytotoxicity of AgNPs was evaluated using an MTT assay on various cancer cell lines (KAIMRC2, MDA-MB231, MCF-7, HCT-116, and MCF-10A). Liquid Chromatography-Mass Spectrometry (LC-MS) was employed to identify biometabolites. Additionally, the antibacterial activity of the prepared nanoparticles was evaluated against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) bacterial strains.

Result:

FTIR analysis confirmed the successful synthesis of AgNPs. The average size of AgNPs synthesized was 54.30 nm. SEM and EDX analysis showed speciallyshaped NPs and the presence of several bio-molecules, mainly carbon, oxygen, and silver. The MTT assay demonstrated the cytotoxic activity of AgNPs synthesized from R.S. extract against various cancer cell lines, with IC50 values of 204.5 μg/mL, 154.7 µg/mL, and 168.1 μg/mL, 162.9 μg/mL, 321 μg/mLrespectively. The cytotoxicity was further enhanced after coupling the R.S. extract with AgNO3. Additionally, AgNPs exhibited antimicrobial activity against S. aureus and E. coli strains, with larger zones of inhibition (19mm, 20mm) compared to the crude extract (13mm, 10mm).

Conclusion:

Our study shed light on the potential use of medicinal plant-encapsulatednanoparticles for treating fatal human diseases. The utilization of R.S. extract in the synthesis of AgNPs demonstrated promising cytotoxic activity against various cancer cell lines. Moreover, such AgNPs treated with R.S. extract enhanced antimicrobial activity against pathogenic strains, particularly S. aureus, and E. coli.

Coumarins are natural or synthetic compounds with a variety of biological applications, from fluorescent probes to therapeutic agents. Our group has been studying the importance of this moiety in the development of drugs targeting neurodegeneration. Based on the structure of the acenocoumarol, a frequently prescribed oral anticoagulant to treat and prevent thromboembolism, nitro groups have been commonly introduced in coumarin-containing compounds. Therefore, the assessment of their safety for humans is essential.^1,2

In the current work, twelve hydroxy- and nitro-substituted arylcoumarins have been synthetized, and cytotoxicity and hemolytic effects have been studied. Human embryonic kidney cells (HEK-293, strain ATCC CRL1573) and human red blood cells (RBC) have been used for the in vitro assays. Compounds were plated as a 2-fold dose response from 32 to 0.25 μg/mL, with a maximum of 0.5% DMSO. Values of CC₅₀ (cytotoxicity) and HC₁₀ (haemolytic activity) are presented in this communication.

⁽¹⁾ Martins Castanha AP, Moura Almeida-Terassi L, Guardado-Yordi E, Matos MJ, Maistro EL. Cytogenotoxicity assessment of 3-(3,4-dihydroxyphenyl)-7,8-dihydroxycoumarin on HepG2/C3A cells and leukocytes. J Appl Toxicol 2023, 43, 323−334. DOI: 10.1002/jat.4384.

⁽²⁾ dos Santos Silva E, Matos MJ, Maistro EL. Evaluation of in vitro Cytotoxic and Genotoxic Effects of the 3-(3,4-Dihydroxyphenyl)-8-hydroxycoumarin. J Appl Toxicol 2023. DOI: 10.1002/jat.4479.

According to research, thiosalicylic acid has anti-inflammatory, antioxidant, and analgesic effects. Additionally, some of its derivatives have shown significant antimicrobial and antitumor activity. In vitro studies have also shown that S-alkyl derivatives of thiosalicylic acid exhibit moderate and dose-dependent cytotoxic effects on human colon and lung carcinoma cells. In this reserach, we utilized various spectroscopic methods and molecular docking simulation to examine the binding interaction between human serum albumin (HSA) and potential biologically active isopropyl derivatives of thiosalicylic acid (ligand, L). To analyze the quenching mechanism, the association constants and number of binding sites were utilized based on the obtained results. The tested L and HSA had a static fluorescence quenching mechanism, while their binding processes were spontaneous. Additionally, UV-Vis absorption spectroscopy revealed that the binding of the tested L induced slight conformational changes in HSA.

Thiosalicylic acid is known for its diverse pharmacological properties and its frequent use in various synthetic conversions. The unique structure of thiosalicylic acid permits the incorporation of diverse S-alkyl derivatives, resulting in favorable chemical characteristics for numerous applications. Therefore, affinity for one of the binding sites of human serum albumin (HSA) of isoamyl derivative of thiosalicylic acid (ligand, L), were examined. Binding mode of compound L was determined using fluorescence spectroscopy. Warfarin was used as a marker for Sudlow’s Site I (subdomain IIA), while ibuprofen was used as a marker for Sudlow’s Site II (subdomain IIIA). Obtained values of Ka suggested that investigated compound bind to HSA. Results of site marker competitive experiments showed that the tested L bind to HSA in domain IIA (Site I). The presented results will help to improve the research of the mechanism of the interaction between transport proteins and similar compounds.

Esculin is a glycosylated coumarin whose range of bioactivity has already been demonstrated in murine models. However, these classes of molecules have low solubility in both hydrophilic and hydrophobic media, which hinders their industrial application. Acylation reactions allow coumarins to become more lipophilic by incorporating acyl radicals into these compounds, consequently enhancing their solubility. Biocatalytic processes are widely used to acylate molecules due to the characteristic selectivity of enzymes, with a special focus on transesterification reactions that can yield excellent results. In this regard, the objective of the present study was to promote the enzymatic acylation of esculin. Vinyl acetate was used as the acylating agent, and Novozyme 435, an immobilized lipase, served as the catalyst, with both reagents solubilized in THF. The biocatalytic transformation occurred at a temperature of 60°C, six hours after the start of the reaction. The products were isolated using high-speed countercurrent chromatography. The chemical structures of esculin monoacetate and diacetate were determined through 1H and 13C and two-dimensional Nuclear Magnetic Resonance, as well as liquid chromatography coupled with mass spectrometry. The formation of the products was monitored by thin-layer chromatography and high-performance liquid chromatography coupled with diode arrays at regular time intervals between 0 and 8 hours of the reaction to obtain retention time data for kinetic analysis. The λmax values of esculin monoacetate were found to be 196, 225, and 334 nm, while those of esculin diacetate were 196, 228, and 335 nm. The evaluated methods confirmed that one reaction product was esterified at the 6'OH position (RT: 10.01 min and m/z 382.93 [M-H]-) of the glycosidic portion of esculin, and the other at both the 6'OH and 3'OH positions (RT: 12.67 min and m/z 424.93 [M-H]-) in that moiety of the molecule.