Russian Journal of Bioorganic Chemistry最新文献

Objective: Efficient synthesis of isatin Schiff’s bases (IIIa–IIId) and isatin-derived 1,3,4-oxadizoles (IVa–IVd) and evaluation of their in vitro antibacterial, antifungal, and anti-TB activities. The molecular docking studies were performed with protein New Delhi Metallo-Beta-lactamase-1 and Mycobacterium tuberculosis enoyl reductase and molecular dynamics simulation. Methods: The chemical structures were confirmed by IR, NMR, and mass spectroscopic techniques. The biological screenings were studied for the foresaid compounds for their in vitro antibacterial, antifungal, and anti-TB activity using MIC method. Molecular docking and dynamics simulation studies were conducted using AutoDock software with proteins New Delhi Metallo-Beta-lactamase-1 (NDM-1, PDB ID: 3ZR9) and Mycobacterium tuberculosis enoyl reductase (INHA, PDB ID: 4TZK). Results and Discussion: The compounds (IVa–IVc) displayed excellent in vitro antimicrobial activity. Also, the compounds (IVa–IVc), were found to be most active with a MIC of 3.125 µg/mL. For the docked proteins, all the compounds exhibited a substantial binding affinity. Further, molecular dynamics were disclosed for compounds (IVa–IVc). Conclusions: The compounds (IIIa–IIId) and (IVa–IVd) were synthesized from substituted isatins, p-amino benzoic acid, and isoniazid with moderate to excellent yields. These reactions are simple, convenient, and hitherto novel. In docking studies the compounds (IVa–IVc) showed excellent bind affinity towards the enzymes.

Ubiquitination, one of the most common posttranslational modifications of proteins, has a significant impact on their functions, such as stability, activity, and cellular localization. Disorders in the ubiquitination and deubiquitination processes are associated with various oncological and neurodegenerative diseases. The complexity of ubiquitin signaling, specifically monoubiquitination and polyubiquitination with different lengths and types of ubiquitin– ubiquitin linkages determines their versatility and ability to regulate hundreds of different cellular processes. Advanced biochemical, mass spectrometric, and computational studies are required for in-depth understanding of the mechanisms of assembly and disassembly, as well as detection of ubiquitin chains and their signal transmission. Recent scientific achievements make it possible to identify protein ubiquitination and the structure of ubiquitin chains, but there are a lot of issues in this area to be clarified. The present review provides a detailed analysis of the current understanding of the architectonics of ubiquitin chains.

Objective: This study involved synthesis of a new series of different five-membered heterocyclic derivatives, testing their antioxidant activity, and examining their potential in vitro antimicrobial agents. Methods: The synthesis of the derivatives involved a three-step process. Initially, succinyl chloride was reacted with methanol, followed by a reaction with 80% hydrazine hydrate through a nucleophilic addition-elimination mechanism, resulting in the formation of succinohydrazide (I). This compound was then employed as a precursor for the synthesis of Schiff bases (II), and (III) by reacting it with m-nitro benzaldehyde and p-nitro benzaldehyde. Following this, a ring closure reaction was applied using thioglycolic acid, glycolic acid, and glycine, resulting in the synthesis of different five-membered heterocyclic rings (IV–IX). Results and Discussion: The formation of the prepared derivatives was confirmed by FT-IR, ¹H NMR, and ¹³C NMR spectroscopy. Comparative analysis with L-ascorbic acid as a standard revealed that all the prepared compounds exhibited excellent antioxidant activities. In terms of antimicrobial activity, the tested derivatives showed moderate activity against both positive and negative types of bacteria, when compared to the reference drug Ciprofloxacin. Additionally, the antifungal test showed moderate activity for all the tested compounds against a specific pathogenic fungus, with Clotrimazole being as the reference drug. The antimicrobial activity of the synthesized compounds was found to be dependent on the type of heterocyclic rings containing S, O, and N atoms. These atoms were observed to enhance antimicrobial activity by donating electrons and becoming active. Additionally, the presence of active functional groups such as C=O, NO₂, and C=N contributed to this observed result. Conclusions: All of the synthesized compounds have demonstrated excellent antioxidant agents. Most of them have shown promising antimicrobial activity against certain bacteria strains, and effectiveness against a pathogenic fungus.

Objective: This research aims to synthesize and characterize a new series of bioactive quinazoline derivatives, including Schiff bases, biquinazolinone, and benzothiazine, and to evaluate their bioactivity as antioxidants through both in silico and in vitro investigations. Methods: The new derivatives were synthesized with high yields by reacting Schiff base derivatives of quinazoline with 2-aminobenzoic acid and 2-mercaptobenzoic acid. The characterization of the prepared derivatives was carried out using FTIR, ¹H NMR, and ¹³C NMR techniques. In silico investigations included assessing pharmacokinetic and pharmacodynamic properties through the SwissADME online server and conducting molecular docking studies with the tyrosinase enzyme. In vitro assessments involved evaluating antioxidant activity using the total antioxidant capacity method and the DPPH scavenging activity method. Results and Discussion: In silico analysis revealed favorable pharmacokinetic and pharmacodynamic properties for all compounds. Compounds (III) and (IV) exhibited acceptable pharmacological characteristics. Molecular docking studies showed good docking scores for all compounds with the tyrosinase enzyme. In vitro assessments demonstrated noteworthy to excellent antioxidant activity for all compounds, with compounds (III) and (IV) exhibiting very strong activity compared to the standard reference, ascorbic acid. Conclusions: The synthesized quinazoline derivatives exhibit promising bioactivity as antioxidants, supported by both computational and experimental assessments. These findings suggest their potential for further exploration in the development of antioxidant agents, with particular emphasis on the notable performance of compounds (III) and (IV).

Objective: The aim of this study is to produce novel 4(3H)-quinazolinone derivatives, analyze their efficacy as antibacterial and antifungal agents, and investigate their antioxidant abilities. Methods: New quinazolinone derivatives were synthesized by mixing Schiff bases with three different chemicals: phenyl isocyanate, 4-chlorophenyl isocyanate, and phenyl iso thiocyanate. This resulted in the formation of compounds (VIa–VIb), (VIIa–VIIb), and (VIIIa–VIIIb). The efficacy of these synthesized compounds against bacteria and fungi was evaluated. Subsequently, their antioxidant activity was assessed using the DPPH scavenging method. Results: FT-IR, ¹H NMR, and ¹³C NMR spectroscopy were used to investigate all the prepared derivatives. Compounds (VIIb), (VIIIa), and (VIIIb) exhibited good antioxidant activity when compared to ascorbic acid. Discussion: The presence of the quinazolinone nucleus in some compounds gives them good biological properties as antimicrobials and antioxidants. Conclusions: All the synthesized compounds were highly effective at killing fungi, especially Rhizopus microrhizosporium, and Candida. Most of them were also very effective at killing bacteria like E. coli, Bacillus cereus, and Pseudomonas aeruginosa. Although most of these compounds have relatively moderate effectiveness against Staphylococcus aureus, some of them contain good antioxidants, particularly compound (VIIIb).

Objective: Resveratrol, a natural product found in plants, is a polyphenolic compound with strong antioxidant activity. In order to enhance the antioxidant activity of resveratrol, we have used a natural product emodin, which has multiple hydroxyl group structure similar to resveratrol. Methods: In this study, we investigated the antioxidant activities of resveratrol and emodin in vitro respectively, including their abilities to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals, hydroxyl radicals, and superoxide radicals. Results and Discussion: our results demonstrated that the combination of resveratrol and emodin significantly enhances antioxidant activity. And the process of their DPPH radical scavenging follows a first-order reaction kinetics equation. Finally, a possible mechanism for the scavenging of DPPH free radicals by resveratrol and emodin was proposed. Conclusions: We found that emodin combined with resveratrol can increase antioxidant activity. This study provides a new sight to enhance antioxidant activity.

Optical microscopy has undergone significant changes in recent decades due to the improved diffraction limit of optical resolution and the development of high-resolution imaging techniques referred to under the common name fluorescence nanoscopy. These techniques allow researchers to observe in detail biological structures and processes at a nanoscale level to reveal previously hidden features and answer basic biological questions. The advanced methods of fluorescent nanoscopy include STED (Stimulated Emission Depletion) Microscopy, STORM (STochastic Optical Reconstruction Microscopy), PALM (Photo-activated Localization Microscopy), TIRF (Total Internal Reflection Fluorescence) microscopy, SIM (Structured Illumination Microscopy), MINFLUX (Minimal Photon Fluxes) microscopy, PAINT (Points Accumulation for Imaging in Nanoscale Topography), and RESOLFT (REversible Saturable Optical Fluorescence Transitions) microscopy, and others. Most these methods make it possible to obtain 3D images of the objects under study. In this review, we consider the principles of these methods, their advantages and disadvantages, and their application in biological research.

Objective: Microbial infections and the cancer are the biggest health concerns now days. It has been reported that 19.3 million new cancer cases and approximately 10 million deaths occurred due to cancer. The pyrimidine and their derivatives have been investigated a lot by the researchers due to their versatile chemotherapeutic effects. The unmet demand for the new antimicrobial and anticancer chemotherapeutic agents and the versatile pharmacological applications of pyrimidine derivatives prompted us to perform the synthesis and biological assessment of some novel 3-(substitued)-6-(substituted)pyrimidin-2-yl)-2-phenylthiazolidin-4-one. Methods: As a part of or investigation to find out some novel antimicrobial and anticancer agents, in this paper we focused on the synthesis of some novel 3-(substitued)-6-(substituted)pyrimidin-2-yl)-2-phenylthiazolidin-4-one derivatives. Additionally, the compounds were screened virtually for the drug likeness properties and characterized by FT-IR and NMR. Antimicrobial and anticancer studies were performed using the methods of disc diffusion, macro dilution and MTT assay. Results and Discussion: The virtual screening results revealed that all the compounds were found under the zone of inhibition for an active drug molecule. It was observed that the analytical data strongly supported the structure of the aimed compounds. Among all the synthesized compounds, the compounds (IX–XII), (XIV–XVI) were possessed very good antimicrobial effects. Some of these members represented even better antimicrobial potential against some specific pathogens. The compound (XII) was observed to be the most active compound of the series against almost all bacterial pathogens. The MTT findings revealed that the compounds (III), (IX), (X), (XII) were possessed similar IC₅₀ to the reference drug doxorubicin. Conclusions: The antimicrobial and anticancer findings were promising and it was believed that further studies with these compounds aiming in vivo analysis will be helpful in producing the novel antimicrobial and anticancer agents.

Objective: Scorpion α-neurotoxins (ɑ-NaTx) inhibit the inactivation of voltage-gated sodium channels (Na_v) with variable efficiency between organisms and channel isoforms. Based on our previous results, we hypothesized that the derivative of the ɑ-NaTx called BeM9 with two amino acid residues substituted with glycine (A4G and Y17G; BeM9^GG) should be more selective for the mammalian channels. Surprisingly, BeM9^GG lost its activity on the cardiac isoform Na_v1.5. We provide a possible explanation of this effect, taking into account the published structures of ɑ-NaTx–Na_v complexes. Methods: We produced BeM9^GG in Escherichia coli as a fusion protein with thioredoxin, which was cleaved by cyanogen bromide. We purified BeM9^GG using chromatography and measured its activity on Na_v isoforms expressed in Xenopus laevis oocytes by the two-electrode voltage clamp technique. We performed computer modeling of ɑ-NaTx–Na_v complexes to figure out the peculiarities of toxin interactions with Na_v1.5. Results and Discussion: Using electrophysiology, we tested BeM9^GG on Na_v, and unexpectedly observed compromised activity on Na_v1.5. We compared the structures of available ɑ-NaTx–Na_v complexes to explain this effect. In case of Na_v1.5 the toxin-binding site is immersed deeper in the membrane. We explain this by sequence variations in two positions of the voltage-sensing domain IV of Na_v: in Na_v1.5 corresponding residues have shorter side chains, permitting the toxin to sit deeper. At the same time, residue Y17 in BeM9, which is missing in BeM9^GG, interacts with the hydrophobic core of the membrane and may play a significant role in its activity against Na_v1.5. Conclusions: The role of the membrane in ɑ-NaTx interactions with Na_v has been overlooked. It is especially important in case of Na_v1.5, where the tripartite toxin–ion channel– membrane complex is formed. Our study will be of help for the future design of selective Na_v ligands.

Objective: The synthesis, antibacterial, and antioxidant assessment of novel tetrazole derivatives with the 2-amino-5-(4-nitrophenyl)-1,3,4-thiadiazole moiety are the main objectives of this work. Methods: A multi-step procedure was used to synthesis the desired compounds, beginning with the creation of the thiadiazole core and ending with the functionalization of tetrazole rings. Results and Discussion: 2-Amino-5-(p-nitro phenyl)-1,3,4thiadiazole (I) was prepared by reacting p-nitro benzoic acid with thiosemicarbazide in the presence of POCl₃. Compound (I) then underwent a reaction with 2-chloroacetohydrazide to produce 2-(5-(4-nitrophenyl)-1,3,4thiadiazol-2-yl)acetohydrazide (II). Several new Schiff bases (IIIa–IIId) were synthesized by reacting compound (I) with different aromatic aldehydes. In contrast, tetrazole derivatives (IVa–IVd) were produced by reacting Schiff bases derivatives (IIIa–IIId) with sodium azide. NMR and infrared spectroscopy were among the spectroscopic methods used to confirm the structures of the produced compounds. Using standard disc diffusion and broth dilution techniques, the antibacterial activity of these derivatives was evaluated against a panel of Gram-positive and Gram-negative bacteria. Additionally, radical scavenging assays was used to assess the antioxidant potential. The results showed that a number of the produced tetrazole derivatives have notable antioxidant and antibacterial properties. Conclusions: These results imply that 2-amino-5-(4-nitrophenyl)-1,3,4-thiadiazole scaffold-containing tetrazole derivatives may be good candidates for the synthesis of novel medicinal medicines with combined antioxidant and antibacterial capabilities.