Russian Journal of Bioorganic Chemistry最新文献

Objective: Stability and monodispersity are important properties of nanoparticles and nanocomposites, that ensure the reliability of their application in biological systems and the reproducibility of results. The preparation of non-agglomerated oligonucleotide-containing nanocomposites based on anatase titanium dioxide nanoparticles (Ans~ODN) is the aim of this study. Methods: The immobilization of oligodeoxynucleotides on TiO₂ nanoparticles was studied by dynamic light scattering and transmission electron microscopy. The antiviral activity of the synthesized samples was evaluated against VERO cells infected with herpes simplex virus type 1. Results and Discussion: The effect of NaCl on the agglomeration of the nanoparticles and the nanocomposites in aqueous solutions was studied. The presence of NaCl leads to agglomeration of the nanoparticles and the nanocomposites. It was shown that the nanocomposites are formed in an aqueous solution in the absence of NaCl. A comparison of the biological activities of the nanocomposites prepared in water and in saline solution was carried out on the example of inhibition of replication of the herpes simplex virus type 1 in the cell culture. The studied nanocomposite, regardless of the preparation method (in water or in 0.9% NaCl), inhibited virus replication by 4.5 orders of magnitude when used 1 day after preparation. After 10 days of storage, the activity of the sample prepared in saline solution was two orders of magnitude lower than that of the active sample prepared in water. Conclusions: We have developed a method for the preparation of non-agglomerated oligonucleotide-containing nanocomposites based on anatase nanoparticles and demonstrated their potential use for the study of their biological activity. Unlike nanocomposites prepared in the presence of the salt, which lose their efficacy during storage, nanocomposites that are not prone to agglomeration can be obtained in water for future use.

Objective: The objective of this study is to design and synthesize novel pyridazinone derivatives through Buchwald coupling reaction, followed by characterization using ¹H, ¹³C NMR, and LCMS. We aim to evaluate the potential antiviral activity of these compounds against SARS-CoV-2. Methods: The target protein 6LZG (SARS-CoV-2) was selected for docking studies. The synthesized compounds were docked using a molecular docking software, employing appropriate scoring functions, and parameters. Docking results were compared with those of the standard antiviral drug Remdesivir to evaluate relative potency. Results and Discussion: The molecular docking results indicated that the compound (VIIc) and (VIIe) displayed significant binding affinities for the SARS-CoV-2 protein 6LZG. Comparative analysis showed that compound (VIIc) and (VIIe) outperformed the standard drug Remdesivir in terms of binding energy, suggesting a potentially greater efficacy against the virus. In silico ADMET studies demonstrated favorable pharmacokinetic profiles for the synthesized compounds. Conclusions: The study highlights the promising antiviral activity of the synthesized pyridazinone derivatives against SARS-CoV-2.

Objective: This study aimed to synthesize hybrid compounds incorporating indole, oxadiazole, and benzamide moieties, leveraging their known biological activities, to evaluate their potential as tyrosinase inhibitors. Methods: A convergent synthetic approach was employed to develop the hybrid compounds. Structural confirmation was achieved through infrared spectroscopy (IR), proton nuclear magnetic resonance (¹H NMR), carbon nuclear magnetic resonance (¹³C NMR), and elemental analysis (CHN). The inhibitory effects on tyrosinase were assessed using enzyme kinetics, with Lineweaver-Burk plots utilized to determine the mechanism of inhibition. Results and Discussion: The synthesized bi-heterocyclic benzamides demonstrated excellent inhibitory activities against tyrosinase compared to the standard control. Compound (VIIIf) exhibited non-competitive inhibition, forming an enzyme-inhibitor complex, with an inhibition constant (K_i) of 0.0033 µM. Computational analysis indicated favorable binding energy values for these compounds. The study highlights the promising potential of these hybrid molecules as effective tyrosinase inhibitors. The structure-activity relationship analysis suggests that the incorporation of indole, oxadiazole, and benzamide moieties enhances the inhibitory efficacy against tyrosinase, which is crucial for developing treatments for skin disorders. Conclusions: The synthesized indole-oxadiazole-benzamide hybrids are identified as potent tyrosinase inhibitors with significant potential as medicinal scaffolds for treating skin conditions. Further investigations into their therapeutic applications are warranted.

Objective: Cancer chemotherapy for the discovery of new antineoplastic drugs is one of the updated areas of medical and pharmaceutical research. Methods: In the current project, a novel series of 1,3-thiazole derivatives were synthesized and their corresponding anticancer activity was evaluated by MTT assay using three cancer cell lines. A2780 (ovarian cancer), PC3 (prostatic carcinoma), and MCF-7 (breast cancer) were utilized for this purpose. Subsequently, Caspase-3 activation, mitochondrial membrane potential (MMP), and generation of reactive oxygen species (ROS) were also explored for some selected active compounds. Results and Discussion: Fortunately, tested compounds were so active against MCF-7 cells compared to other cell lines. Compounds (VI), (VII), (VIII), (IX), and (XII) enhanced Caspases-3 activity in the MCF-7 cell line that 3-Cl analog (VII) was illustrated as the most cytotoxic index against MCF-7 cells. This is while that among the above analogs (VI–IX), and (XII), just and just, 2-F derivative (IV) revealingly reduced the mitochondrial membrane potential (MMP). The current compounds demonstrated better anticancer activity compared to the other thiazole derivatives. Generally, derivatives bearing electron-withdrawing as well as electron-donating groups are active toward cancerous cell lines. Conclusions: The novel 1,3-thiazole derivatives presented in the current paper could be suggested as potential anticancer agents, especially against breast cancer.

Objective: Cumulus cells respond to the effects of hormones and signalling molecules synthesised by the oocyte by changing their expression profile. In turn, cumulus cells control the growth and maturation of the oocyte. Therefore, analysis of the transcriptional profile of cumulus cells is likely to be one of the approaches for non-invasive prediction of oocyte quality in assisted reproductive technology programs. To evaluate the expression of selected genes in cumulus cells in women with primary and secondary types of infertility with positive and negative results of assisted reproductive technologies. Methods: 9 healthy donors and 19 patients undergoing infertility treatment with ART methods participated in the study. RNA was isolated from cumulus cells obtained during oocyte preparation for fertilisation, and cDNA was synthesised and used as a matrix for real-time PCR with primers for AREG, SCD4, PTGS, SCD5, HAS2, VCAN, STAR and two lncRNA genes (ANXA2P2, MALAT1). Results and Discussion: The genes of interest expression did not depend on the type of infertility but rather on the IVF attempt outcome. The panel of mRNA biomarkers (SDC4^upAREG^upMALAT1^{not changed}ANXA2P2^{not changed} ) was associated with poorer oocyte competence prognosis and SDC4^{not changed}AREG^downMALAT1^downANXA2P2^down set of biomarkers was associated with better quality of oocytes. Conclusions: This non-invasive method can be used to access oocyte quality in patients with primary and secondary infertility.

Objective: A newer series of compounds, including 3-benzoyl-5-(substituted-benzylidin)-thiazolidin-2,4-dione (IVa–IVh) and 3-p-tolyl-5-(substituted-benzylidine)-thiazolidin-2,4-dione (Va–Vh), were synthesized through a nucleophilic reaction involving benzoyl chloride and p-chlorotoluene. These compounds were obtained in conjunction with various 5-(substituted-benzylidine)-thiazolidin-2,4-dione derivatives, which were prepared by condensing thiazolidin-2,4-dione with different substituted benzaldehydes. Comprehensive structural characterization was achieved through UV, FT-IR, ¹H NMR, and mass spectroscopy. Methods: Antimicrobial assessment was conducted against a panel of bacterial strains including E. coli, S. aeruginosa, S. aureus, and B. subtilis, as well as fungal strains A. niger and C. albicans. Molecular docking studies were employed to further validate the results. Anticancer activity was evaluated using the sulforhodamine B (SRB) assay on the HEPG2 cell line. Results and Discussion: The synthesized compounds demonstrated significant antibacterial activity against E. coli, S. aeruginosa, S. aureus, and B. subtilis. Furthermore, notable antifungal activity was observed against A. niger and C. albicans. Compound (Vd) displayed exceptional performance in both aspects, confirmed by molecular docking. Additionally, (IVc), (Vc), (IVh), and (Vh) exhibited significant anticancer activity, while (IVd) exhibited moderate activity at varying concentrations. Conclusions: The newly synthesized compounds exhibit promising antimicrobial and anticancer properties, indicating their potential for pharmaceutical applications. This research represents a significant advancement in medicinal chemistry, offering avenues for further drug development and exploration in the field.

Objective: Eugenol (EG) is a significant ingredient in clove oil that is commonly used as a tooth pain reliever. However, topical application of this phenol has been linked to a number of serious negative consequences. Methods: The goal of this study was to position EG into the coumarin nucleus, yielding a precursor and ten variants labeled (EGCOU1–EGCOU10). To validate their molecular structures, the FT-IR, ¹H, ¹³C NMR, and mass spectra were analyzed. The microbiological study was conducted against many pathogens using a growth medium-dilution approach. These include four aerobic bacteria, four anaerobic bacteria, and two fungi. On the other hand, the biosafety study explored the effect of the experimental coumarins on two non-pathogenic aerobic bacteria, three normal cellular populations, and lab-treated human blood. Results and Discussion: The results of the former study indicated that the experimental coumarins demonstrated outstanding antimicrobial activity compared with the standards used, with minor variances. The most efficacy was discovered against the test fungi, followed by aerobic bacteria, and lastly anaerobic ones, with (EGCOU7) having a preferential impact. The biosafety investigation found that the experimental coumarins were extremely biocompatible with the test nonpathogenic bacteria, normal cells, and human blood erythrocytes. Conclusions: Given the above findings, the author concluded that EG transferred into biosafe wide-spectrum antimicrobial agents through its incorporation within coumarin backbones. Among them, the ones with three substituted groups on the off-side aromatic ring showed higher activity than those with one or two groups. Furthermore, among the prior compounds, the one containing di-meta chlorides and mono-para methoxy exhibited the best benefits. These results and conclusions may light the path to covering the negative biological impacts of harmful phenols by housing them in a coumarin framework.

The use of industrial drugs to treat inflammatory diseases, cancer, and diabetes has become controversial because compared with natural products, these drugs have been found to cause adverse side effects. However, an alternative to synthetic medications has been uncovered from natural sources such as kelp, a term used for large brown seaweed, which is a class of seaweed. Although brown algae are one of the most common and largest subgroups used for food, they have been reported to have increased health benefits owing to the high biological activities of the compounds that are extracted from these brown seaweeds. Fucoidan, a major component obtained from various species of brown algae, is a rather varied group of sulfated polysaccharides (SPs) with complex and heterogeneous structures that lack uniformity and have high nutritional value, and health benefits when consumed. This review discusses some of the key areas in which Fucoidan plays a crucial role in promoting human health and its practical applications. As a result, the analytical literature pertaining to the bioactive characteristics of SPs isolated from the Fucaceae, Laminariaceae, Sargassum, and other groups is emphasized, along with information about their prospective biomedical applications as valuable natural resources in the near future for use in human health. Stability studies, Fucoidan structure, Fucoidan and nanoparticles, the biological activity of Fucoidan, the safety of Fucoidan in humans and animals, Fucoidan patents and commercial applications, and the nutraceutical benefits of Fucoidan extract were performed.

Objective: A number of molecules expressed on mammalian cells are involved in the formation of auto-tolerance. These primarily include CTLA-4/B7 and PD1-PD-L1 signaling pathways. Blockers of these signaling pathways, called checkpoint inhibitors (ICTs) of immunity, are used in the clinic for the treatment of various forms of cancer. Antibodies to CTLA-4 cause systemic toxicity and are approved only for the treatment of melanoma. Antibodies against PD1 or PD-L1 have been successfully used for the treatment of various forms of cancer and are characterized by low toxicity. However, the response to therapy using ICT does not exceed 25–30%. The development of more effective approaches to cancer therapy based on PD1/PD-L1 inhibitors requires additional research. The aim of this work was to express the extracellular part of the mouse PD-L1 protein (exPD-L1) and obtain antibodies to PD-L1. Methods: The mouse exPD-L1 protein was obtained and characterized in the bacterial expression system. exPD-L1 protein was used to immunize mice in order to produce anti-PD-L1 antibody producers. Results and Discussion: Using hybridomic technology, 5 clones expressing antibodies to exPD-L1 were obtained. Antibodies of the B12 clone were developed in the ascitic fluid of BALB/c mice and purified by affinity chromatography. The ELISA method for purified antibodies showed specific binding to the exPD-L1 protein and the commercial protein of the extracellular part of the mouse PD-L1. Conclusions: Experiments using flow cytometry and confocal microscopy have shown that the antibodies obtained bind the intracellular form of the PD-L1 protein, unlike commercial antibodies binding the membrane form.