Russian Journal of Bioorganic Chemistry最新文献

Objective: Breast cancer is one of the most prevalent malignancies among women worldwide and a leading cause of cancer-related mortality. The emergence of resistance to existing therapies underscores the need for novel agents. Methods: In this study, gefitinib, a well-established tyrosine kinase inhibitor used in non-small cell lung cancer treatment, was structurally modified to generate a series of 1,2,3-triazole hybrids. All synthesized compounds were characterized and evaluated for their antiproliferative activity against the MCF-7 breast cancer cell line and the LO2 normal hepatic cell line. Results and Discussion: The biological assessment revealed that hybrids 2c and 2l exhibited the most potent anti-proliferative effects against MCF-7 cells, with IC₅₀ values of 8.51 and 8.93 μM, respectively, while showing lower cytotoxicity toward LO2 cells. Both compounds significantly reduced MCF-7 cell viability. Apoptosis analysis demonstrated that compound 2l notably induced apoptotic cell death. Gene and protein expression profiling indicated that 2c and 2l modulated the expression of markers associated with oxidative stress, autophagy, DNA damage, and apoptosis. Staining assays for DNA damage and autophagosome formation further corroborated the anti-proliferative effects of 2c and 2l in MCF-7 cells. Conclusions: These findings suggest that the gefitinib-1,2,3-triazole hybrids 2c and 2l are promising candidates for further investigation as potential anti-tumor agents against breast cancer.

Aminoquinoline derivatives, renowned for their versatile biological activities, are crucial scaffolds in medicinal and material chemistry. These compounds are integral to developing antimalarial, antibacterial, anticancer, and immunomodulatory agents, with prominent examples including chloroquine, neratinib, and imiquimod. Furthermore, aminoquinoline moieties serve as precursors for Schiff bases and their corresponding metal complexes, which exhibit properties such as selective fluorescence sensing, catalytic activity, and enhanced therapeutic potential. This review covers recent advances in synthesizing aminoquinoline-based Schiff bases and their metal complexes, focusing on their structural diversity, coordination chemistry, and reaction mechanisms. It highlights their significant roles in fluorescence-based detection of metal ions (e.g., Fe³⁺, Al³⁺, Hg²⁺) and their application in anticancer, antimicrobial, and antitubercular therapies. The complexation of Schiff base ligands with metal ions often enhances their pharmacological profiles, leading to superior activity compared to the free ligands. By discussing synthetic methodologies, characterization techniques, and bioactivity evaluations, this review provides a comprehensive overview of the potential of aminoquinoline derivatives in drug development and sensor technology, paving the way for innovative applications in therapeutics and diagnostics.

Tuberculosis is a bacterial disease primarily caused by Mycobacterium tuberculosis, which most commonly affects the lungs. Despite the development of various drugs, the disease remains a global public health emergency, as declared by the World Health Organization (WHO). Therefore, research on promising drugs to control and prevent the disease is essential. Hydrazides (R–C(O)–NH–NH₂) are important intermediates. Their condensation with aldehydes or ketones yields hydrazone derivatives, which are a subclass of Schiff bases (compounds featuring an azomethine group, –C=N–). These hydrazide-derived Schiff bases and their metal complexes are promising scaffolds for antitubercular drug discovery. In this review, the antitubercular potential of hydrazides and their complexes is discussed and compared with isoniazid, a standard drug.

Synthetic polymers are derived primarily through chemical processing from fossil fuel-based raw materials. The extensive use of these non-biodegradable synthetic materials in pharmaceutical drug delivery, cosmetics, biomedical applications, and food packaging has caused significant environmental damage and poses potential health risks to living organisms. This calls for alternative, sustainable materials. Biopolymers, as sustainable and renewable polymeric sources, represent a viable alternative to overcome these issues. Recently, chitin, a highly abundant natural amino polysaccharide, and its derivatives have attracted researchers’ attention due to their outstanding properties, such as biodegradability, biocompatibility, non-toxicity, and low cost, which make them ideal candidates for pharmaceutical and biomedical applications. In this review, we selectively highlight the sources, extraction processes, biosynthesis, and properties of chitin and its derivatives. Furthermore, major research on chitin- and chitosan-based nanoformulations for drug delivery in various diseases, such as cancer, leishmaniasis, and microbial infections, is discussed. Similarly, nanoformulations for the delivery of numerous bioactive phytoconstituents, such as curcumin, rutin, ferulic acid, and quercetin, are also reviewed. Additionally, the immunogenicity, cytotoxicity, safety considerations, and clinical outcomes of various trials involving chitin and chitosan are summarized.

Objective: This study aimed to synthesize novel 1,3,4-thiadiazole-based 1-(amino(substituted-phenyl)methyl)naphthalen-2-ols using an ultrasound-assisted approach. The objective was to evaluate their anticancer and antibacterial activities, as well as their molecular interactions and pharmacokinetic properties. Methods: The compounds were synthesized using an ultrasound-assisted approach with silica sulfuric acid as a catalyst. This involved the condensation of aminothiadiazoles and aromatic aldehydes with 2-naphthol. Anticancer activity was tested against A-498 and A549 cell lines, while antibacterial activity was assessed against S. aureus, B. subtilis, E. coli, and P. aeruginosa. Molecular docking studies were performed with target proteins 1KZN, 1BAG, 1D7U, and 2XCT. Additionally, in-silico ADME profiling and structural analysis, including optimized geometries, FMOs, and MEP plots, were carried out. Results and Discussion: The synthesized compounds exhibited promising anticancer activity, with the bromine-substituted derivative IVa being the most potent. Compound IVc showed significant antibacterial activity against all tested strains. Molecular docking results indicated superior binding energies for IVc and IVb, ranging from −7.5 to −8.4 kcal/mol. In silico ADME profiling predicted favorable pharmacokinetic properties. Structural analysis showed that IVc had a reduced energy gap (∆E: 2.1687 eV), lower hardness, higher softness (ɳ: 1.0843 eV, S: 0.9222 eV), and low toxicity (IVb: ω: 0.3675 eV). Conclusions: The synthesized compounds, especially IVa and IVc, showed strong anticancer and antibacterial activities, making them promising candidates for further research. Molecular docking and ADME results support their potential for biological applications. Structural insights suggest that these compounds possess favorable reactivity, stability, and low toxicity, further confirming their potential as bioactive scaffolds for future investigations.

Objective: A novel series of oxazolone-fused 4H-chromene derivatives was synthesized via a piperidine-catalyzed one-pot method using an ethanol–chloroform solvent system. Methods: The compounds were evaluated for their antimicrobial and antioxidant activities, supported by molecular docking and ADMET profiling. Results and Discussion: Compounds 4b and 4c, bearing naphthol substituents, exhibited notable antibacterial, antifungal, and antioxidant effects. Docking studies against Topoisomerase IV (E. coli), CYP51 (C. albicans), and oxidoreductase revealed strong binding affinities: compound 4b showed docking scores of 7.22, 7.14, and 7.92, while 4c scored 7.16, 7.34, and 7.45, respectively. Although 4b demonstrated potent bioactivity, it showed moderate risks of mutagenicity and tumorigenicity, limiting its therapeutic potential. In contrast, compound 4c (2-naphthol derivative) combined strong multitarget activity with a favorable safety profile, highlighting its promise as a lead candidate for further drug development. Conclusions: These results underscore the significance of structural modifications and support the integration of computational tools in early-stage drug discovery.

Objective: In this study, we synthesized five novel triazole derivatives and biologically evaluated their antiurease and antioxidant properties. Methods: Five novel 1,2,4-triazole derivatives (5a–5e) were synthesized and tested for their urease inhibition and antioxidant activities using spectrophotometric methods. Results and Discussion: All compounds exhibited varying degrees of biological activity, with compound 5c demonstrating the most potent urease inhibition and radical scavenging capacity. Statistical analysis confirmed significant differences among the compounds, particularly highlighting the superior performance of 5c. Conclusions: These results suggest that halogen-substituted triazoles are promising candidates for further pharmacological development aimed at oxidative stress-related conditions and urease-associated pathologies.

Objective: The work is focused on protecting plant organisms from acute gamma radiation exposure. The study specifically investigates the use of lignin from wild rosemary (Ledum palustre L.) as a radioprotective agent for the aquatic plant Lemna minor L. Methods: Lemna minor L. was irradiated at doses up to 63 Gy, and the plant biomarkers were assessed. Water-soluble lignin from wild rosemary was used to cultivate plants in aqueous lignin-containing media to evaluate its potential radioprotective effects. Results and Discussion: The study found that water-soluble lignin from wild rosemary is not toxic to Lemna minor L. Pre-cultivating the plants in lignin-containing media resulted in a reduction of radiation-induced damage and an increase in root length, suggesting the adaptogenic and radioprotective properties of lignin. These findings were observed at both the organismal and populational levels. Conclusions: The research for the first time proposed a hypothesis about the radioprotective potential of lignin and experimentally demonstrated that exogenous lignin could protect plant organisms from the effects of acute exposure to high-dose gamma radiation.

The review summarizes the results of research on Sosnowsky’s hogweed processing with the view of extraction of chemical compounds having a raw-material potential for various industrial applications. The presence of carboxylic acids in Sosnowsky’s hogweed makes it suitable for the creation of plant growth stimulants, that of aldehydes and alcohols, for production of selective herbicides, and the presence of coumarins and furocoumarins, for creation of plant protection products with fungicidal, antimicrobial, and insecticidal activity and of anthelmintics. Of greatest interest from the medical and the pharmaceutical industry viewpoint are furanocoumarins (a class of phenolic compounds, coumarin derivatives) isolated from Sosnowsky’s hogweed, which possess antitumor activity and have a potential for application in PUVA therapy, for the treatment of vitiligo and psoriasis. The photosensitizing effect of Sosnowsky’s hogweed furanocoumarins is also of interest for the development of means of disinfecting objects and premises. In the food industry, the presence of low-methoxyl pectic substances in the composition of hogweed provides an opportunity for producing thickeners, and that of sucrose, white sugar on its basis. The high content of cellulose in the biomass of Sosnowsky’s hogweed makes it a valuable raw material for the pulp and paper industry. The chemical composition of Sosnowsky’s hogweed opens up the possibility of producing polymers and composites, as well as flotation reagents on its basis. Considering large biomass of Sosnowsky’s hogweed, its use for energy production, in particular, for obtaining biofuel, is proposed. Heat-insulating composite building mixtures and materials based on modified Sosnovsky’s hogweed can find a wide range of applications in construction.