Russian Journal of Bioorganic Chemistry最新文献

Objective: Polyethylene terephthalate (PET) is thermally stable, biocompatible, transparent in visible and near-infrared light. The study of grafting conditions and the distribution of reactive amino groups on the PET surface without affecting the polymer array makes it possible to change the surface properties in a directed manner. Methods: A method for obtaining active amino groups on the surface of polyethylene terephthalate (PET) substrate by reaction with ethylenediamine was developed. A method for quantitative estimation of the concentration and distribution of chemically accessible amino groups on the surface of PET substrate using cyanine dye Cy5 and digital fluorescence microscopy was developed. Results and Discussion: The PET surface during chemical modification remains without visible damage up to the concentration of amino groups 8 pmol/cm², while surface degradation is observed at higher concentrations. Chemically available amino groups capable of covalently binding to Cy5 dye are distributed unevenly, which is probably due to the presence of amorphous and crystalline areas on the surface of PET substrates. Amino groups can be used for further chemical modification of the PET surface, grafting of various functional groups, and covalent binding to biomolecules, which opens up prospects for the wide use of inexpensive PET as functional substrates in biochips, biosensors, lab-on-a-chip devices, and other biotechnological applications.

Objective: Identification of driver mutations in tumors is an extremely important task in oncology for the choice of treatment strategy and assessment of therapy efficacy. In many cases, especially in disease monitoring, there is a need to detect a small number of copies of the mutant allele against the background of excessive content of wild-type DNA. Methods: Genomic DNA was isolated from tumor tissue in paraffine blocks and amplified using polymerase-chain reaction (PCR) with blocking of wild-type DNA amplification via addition of locked-nucleic acid (LNA) oligonucleotides. Fluorescently labelled PCR-product enriched by IDH-mutant alleles was hybridized on a biochip with immobilized oligonucleotide probes which was able to determine 5 mutations in the IDH1 gene and 2 mutations in the IDH2 gene. Results and Discussion: The method was developed and tested on a collection of 26 samples of paraffinized tumor tissue (glioma, glioblastoma, chondrosarcoma). In three cases, R132C, R132L, and R132H mutations in the IDH1 gene were detected in tumor samples with low representation of the mutant allele. The limit of detection of mutant DNA was determined to be 0.1% in the wild-type DNA background. The advantages of the method are simultaneous analysis of multiple targets, simplicity, reliability, and cost-effectiveness. Conclusions: A highly sensitive method for detecting somatic mutations in the IDH1/2 genes by LNA-mediated blocking of amplification of wild-type alleles and hybridization in a biological microchip was developed. We believe that the method may be useful for detecting low-abundance mutations in tumor samples, as well as in circular tumor DNA.

Objective: The most comprehensive collection of imine was synthesized via a simple, efficient, economical, and rapid method via Schiff base formation. Methods: ((E)-1,5-dimethyl-2-phenyl-4-(((2-phenylimidazo[1,2-a]pyridine-3-yl)methylene)amino)-1,2-dihydro-3H-pyrazol-3-one and their derivatives are synthesized using 4-aminoantipyrine and some substituted 2-phenylimidazo[1,2-a]pyridine-3-carbaldehyde derivatives (SB01) to (SB10). Results and Discussion: The newly synthesized molecules were confirmed using various analytical techniques MS, FT-IR, ¹H, and ¹³C NMR spectrometric analyses. Newly synthesized imidazo[1,2-a]pyridine compounds undergo their biological evaluation with Gram-positive and Gram-negative bacteria as well as antifungal. Conclusions: (SB10), (SB07), (SB05), and (SB01) molecules show good, moderate, and excellent results against tested drugs.

Objective: Modern neurobiology focuses on understanding and preventing neurodegeneration by detecting cellular changes early. Changes in astrocyte ultramorphology may indicate early neurodegeneration, associated with decreased synaptic plasticity and astrocyte aging. While high-resolution techniques like EM and SPM can study these structures, they can’t use fluorescence microscopy for complete 3D analysis. We suggest using fluorescent dye-conjugated nanoantibodies for astrocyte labeling, allowing detailed ultramorphological research with electron, optical, and scanning probe microscopy, plus optical probe nanotomography. Methods: Hippocampi from male C57BL/6 mice were stained using commercial or GFAP-specific VHH-E9 nanoantibodies. The VHH-E9 antibodies were created by synthesizing a nucleotide sequence with added histidines and cysteine, then cloning it into the pET22 plasmid at XbaI and BamHI sites. Escherichia coli Rosetta-gami (DE3) cells were transformed to produce the pET22-VHHE9 strain. The nanoantibodies were produced via autoinduction and conjugated with a fluorophore. Astrocyte morphology was analyzed using the Sholl test with FiJi software. Results and Discussion: Traditional immunoglobulins can cause visualization inaccuracies due to the distance between the label and target protein. Nanoantibody conjugates, being smaller, reduce these errors. Immunostainings with both types showed similar efficiency, as Sholl profiles from different samples aligned within error margins. This supports the effectiveness of the sample preparation method and VHH-E9 nanoantibodies. It also suggests potential for developing similar procedures with fluorescent contrast agents, like semiconductor nanocrystals. Conclusions: To study astrocyte changes in early neurodegenerative stages, we propose combining high-resolution microscopy, optical microspectroscopy, and 3D ultrastructure restoration. Our method, OPNT, uses fluorescence microscopy for localization data, and SPM/UMT for ultrastructure. This involves creating UMT sections for simultaneous OM/SPM analysis and reconstructing them into a 3D array. We efficiently reconstruct 3D astrocyte ultramorphology and developed an immunostaining procedure using camel VHH-E9 nanoantibodies specific to GFAP, highlighting its efficiency and potential with fluorescent semiconductor nanocrystals.

Objective: The objective of the present work was to synthesized, purify, characterize and evaluate the antibacterial, antifungal, and antitubercular activity of some substituted triazoles. Several variants of 3-(4,5diphenyl-4H-1,2,4-triazol-3-yl)pyridine (A1–A9) were synthesized. Methods: Observations were made in differentiation with the reference drug, Griseofulvin (200 µg/mL). The encouraging results from the antibacterial studies impelled us to go for preliminary screening of synthesized compounds against M. tuberculosis H37Rv were performed by LJ agar (MIC) method. Results and Discussion: All of the prepared analogues were tested for their antibacterial efficacy against the pathogenic germs S. aureus and E. coli (Gram-negative) using Norfloxacin (200 µg/mL) as standard. Conclusions: Compounds (A2) and (A4) derivatives showed better antibacterial activity as compared to other derivatives towards both Gram-negative and Gram-positive bacterial strain. Compounds (A1), (A3), and (A5) were also retained good antibacterial activity. All scaffolds have promising antibacterial activity because of electron donor groups such as hydroxy and phenyl. Similarly (A1), (A3), and (A7) have shown significant and better antimycotic activity against Aspergillus niger and Candida albicans. On the basis of preceding evaluation of the antitubercular activity revealed, following observations were made in comparison to the standard drug streptomycin, the derivatives (A1), (A3), and (A6) have shown promising and better result as compared to the other derivatives. Derivative (A4) represented considerable binding with InhA, the enoyl acyl carrier protein reductase (PDB ID: 2X22) from Mycobacterium tuberculosis as denoted by stable molecular dynamics of 100 ns.

Paclitaxel is one of the most widely utilized anticancer drug. It displays a range of antitumor action, particularly against ovarian cancer, urologic malignancies, head tumor, and Kaposi’s sarcoma. However, due to its highly lipophilic nature, poor fluid dissolvability of less 0.01 mg/mL and lack of ionizing functionalities which may enhance its solubility, there are substantial challenges associated with Paclitaxel delivery. Paclitaxel exhibited promising effects when formulated in combination with ethanol and Cremophor EL, as Taxol®. However, it is associated with various side effects, including hypersensitivity, hypotension, and peripheral neuropathy. The albumin-based Paclitaxel, Abraxane®, is a superior alternative to Taxol® as it diminishes the side effects related to Cremophor EL. Abraxane® is regarded as the gold standard for cancer treatment, but its 21% response rate suggests that more research is needed. Furthermore, the large-scale clinical use of this drug has faced considerable delay because of the absence of suitable delivery vehicles. Therefore, necessitates is the development of an alternate form of Paclitaxel that has both superior aqueous solubility as well as fewer side-effects. During the last decade, various methodologies have been explored to improve Paclitaxel’s solubility with the help of co-solvents and inclusion complexes. Additionally, various methodologies report of passive targeting of cancer cells using nanoparticles, nanosuspensions, Rotaxane (a mechanically interlocked molecular system), liposomes, micelles, emulsions, gels, pastes, etc. Herein, we have comprised a brief report on various delivery techniques for Paclitaxel with improved therapeutic outcomes.

Objective: Novel azo-linked substituted sulfonamides were synthesized via diazo coupling with the molecular formula (C₉H₁₀N₄O₂S₂, C₁₁H₁₁N₃O₂S) and characterized by FT-IR, UV-vis, HR-MS, and ¹H NMR spectroscopy techniques. The photophysical studies were carried out using experimental techniques. Absorption and fluorescence maxima of all the synthesized molecules were determined by using different solvents. Our synthesized mono-azo derivatives are interested in identifying the cellular target site for sulfonamides (F1-F2) and (P1-P2). The newly synthesized compounds were examined for their in vitro antibacterial activity against Staphylococcus aureus and Escherichia coli strains. Methods: In this study, we focused on the sulfonamide architecture. Antibacterial activity of compound (F1), (F2), (P1), and (P2) derivatives was studied by measuring the diameter of the inhibition zone, using the Disc-agar diffusion method. Results and Discussion: Density functional theory was used to demonstrate the electronic and optical properties of the synthesized molecules. In the correlation between the HOMO–LUMO energy gap, the derivative (F1) shows a higher (3.9866 eV) and (F2) shows a lower (3.2063 eV) excitation energy. The synthesized compound (F1) looks into antibacterial activity, exhibited more zone inhibition 25 mm in the concentration 75 µL/mL in gram-negative bacteria when compared with the common antibiotic Ciprofloxacin. Additionally, the results emerged from the in silico molecular docking studies the compound (F2) showed highest binding energy against cyclin-dependent kinase (ΔGb = –9.8 kcal/mol). Conclusions: The synthesized four mono-azo sulfonamide derivatives (F1), (F2), (P1), and (P2) are reported in photophysical, CDFT, antibacterial, and molecular docking studies with relevant results.

Objective: In the current situation, human beings face challenges in the design and fabrication of new pyridine-based multifunctional hybrids for various applications. Pyridine-based scaffolds sparked tremendous scientific interest in discovering new active components in medicinal areas. Methods: Here we report the synthesis of pyridine-clubbed hydrazide with substituted aldehyde building blocks via a green chemistry approach. In this work, we demonstrate the synthesis of a small library of compounds via enaminone to Schiff base formation by using microwave techniques. Moreover, the final moieties’ drug-likeness profile and toxic effects were assessed by in silico ADMET prediction analysis. Results and Discussion: Synthesized compounds were characterized by MS, FT-IR, ¹H, ¹³C NMR, and other analytical techniques. Furthermore, synthesized compounds (IVa–IVj) were screened against Gram-positive, Gram-negative, and fungal stains for their antimicrobial assay using the broth dilution method and Ciprofloxacin, and nystatin were used as standards. Conclusions: The result shows that at a concentration of 25 µg/mL, the compounds with substitutions in thio, indole, and pyridine (IVc), (IVd), and (IVh) had excellent antibacterial activity and compounds with substituted chloro and methoxy (IVb) and (IVi) exhibited excellent antifungal activity at a concentration of 100 µg/mL.

Objective: Usnic acid, one of the most common and famous lichen acid and its Schiff base derivatives have various pharmacological activities such as analgesic, antibacterial, antiprotozoal, anti-inflammatory, anticholinergic, antiulcer, antioxidant, antiproliferative, and apoptotic properties. Dopamine, histamine and vanillylamine are the molecules that have important physiological properties in living organisms. Thus, in the current study, we aim to explore the potential pharmacological activities of novel Schiff base derivatives of usnic acid (I). Methods: Three novel Schiff base derivatives (II–IV) of usnic acid (I) were synthesized via the condensation of dopamine, histamine and vanillylamine. In vitro enzyme inhibitory effects on α-glycosidase, α-amylase, monoamine oxidases (MAO-A and MAO-B), and cholinesterase’s (AChE and BChE) and antioxidant potentials of the compounds (I–IV) were evaluated. Results and Discussion: Among the tested compounds, only ligand (II) has an antidiabetic potential inhibiting strongly both α-glycosidase and α-amylase enzymes. All of the tested molecules exhibited a remarkable antidepressant effect by inhibiting MAO-A activity; however their effects were determined to be lower than that of clorgyline. On the other hand, the antiparkinson’s and neuroprotective capabilities of (I–IV) were found to be much weaker as compared with those of pargyline and galantamine. The antioxidant potencies of (I–IV) were carried out and the compounds, (II) and (IV) acted as potent antioxidant agents by scavenging the ABTS and DPPH radicals more strongly than BHA and trolox. Conclusions: Our results point out the compound (II) is a candidate molecule for further in vitro and in vivo pharmacological studies due to its potent antidiabetic, antioxidant as well as remarkable antidepressant potentials.

Objective: Novel 2,3-disubstituted 4-oxoquinazoline-3(4H) derivatives containing oxadiazole, thiazolidinone ring, the 4-oxoquinazoline-3(4H) Schiff bases, and carbothioamide structure were synthesized. All the synthesized compounds’ urease and acetylcholinesterase enzyme inhibitions were evaluated in vitro. Methods: The chemical structures of the synthesized compounds were confirmed using IR, ¹H, and ¹³C NMR spectral methods. For all newly synthesized compounds, the urease enzyme inhibition activity was measured using the Weatherburn method, and the acetylcholinesterase enzyme inhibition activity was measured using the Ellman method with slight modifications. Results and Discussion: All newly synthesized compounds showed urease enzyme inhibition in the range of IC₅₀ = 11.00 ± 0.10 to 17.45 ± 0.25 µg/mL compared to standard thiourea (IC₅₀ = 15.75 ± 0.25 µg/mL). Among the synthesized compounds, quinazolinone containing oxadiazole ring (IVa–IVd) and thiosemicarbazide structure (IXa–IXd) showed the most inhibition. Most of the synthesized compounds exhibited good inhibitory activities against acetylcholinesterase compared to the standard inhibitor Galantamine (IC₅₀ = 20.45 ± 0.25 µg/mL), in the range of 16.44 ± 0.26 to 30.50 ± 0.50 µg/mL. Furthermore, the molecular docking study was performed to determine the interaction modes of newly synthesized compounds at the active site of the target enzymes. ADMET properties were calculated to evaluate the drug-likeness of all compounds. Conclusions: In this study, a new series of quinazolinone derivative compounds with potentially active antiurease and antiacetylcholinesterase inhibitions were synthesized, consistent with in silico studies.