Russian Journal of Bioorganic Chemistry最新文献

{"title":"Synthesis of Reactive Pegylated Indocyanine Dyes","authors":"V. E. Shershov,&nbsp;V. E. Kuznetsova,&nbsp;G. F. Shtylev,&nbsp;I. Yu. Shishkin,&nbsp;R. A. Miftakhov,&nbsp;V. I. Butvilovskaya,&nbsp;I. V. Grechishnikova,&nbsp;A. A. Stomakhin,&nbsp;O. A. Zasedateleva,&nbsp;A. V. Chudinov","doi":"10.1134/S106816202460716X","DOIUrl":"10.1134/S106816202460716X","url":null,"abstract":"<p><b>Objective:</b> The aim of this study was synthesis and selection of conditions for isolation and purification of fluorescently labeled polyethylene glycol with a reactive carboxyl group for labeling biomolecules. Pegylated nucleotides, which are part of drugs, allow targeted drug delivery to specific organ, prolong the half-life, reduce immunogenicity, and increase stability. <b>Methods:</b> The reaction product was isolated using three-stage chromatographic purification: reverse-phase column chromatography with C18-RP sorbent, ion exchange chromatography on DEAE-cellulose DE52 sorbent, and column chromatography on silica gel. <b>Results and Discussion:</b> An activated derivative of an indocarbocyanine dye was preliminarily synthesized and then used to obtain fluorescently labeled polyethylene glycol with a reactive carboxyl group. The conjugation reaction of the activated indocyanine dye ester with a 10-fold excess of polyethylene glycol was performed in DMF in the presence of DIPEA at 50°C for 12 h. The reaction in hexametapol resulted in the formation of only a by-product with a quantitative yield. Conducting the conjugation reaction of PEG with indocarbocyanine dye in one stage without isolating the intermediate activated ester of the dye in an aqueous organic solvent led to the formation of the target product in trace amounts. <b>Conclusions:</b> The synthesis of fluorescently labeled polyethylene glycol with a reactive carboxyl group for subsequent modification of single-stranded DNA molecules was carried out, and conditions for its isolation and purification were selected. The availability of an effective and feasible method for producing reactive pegylated indocyanine dyes, which provides a possibility to control the quality of intermediates at each stage of the synthesis, will expand the screening of therapeutic drugs with specified characteristics.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1586 - 1590"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Anti-Leukemia Activity of N-[1-(1-Adamantyl)ethyl]-3-hydroxylup-20(29)-en-28-amide","authors":"K. A. Barmina,&nbsp;I. I. Kulakov,&nbsp;V. S. Vlasenko,&nbsp;N. N. Novikova,&nbsp;E. A. Vishnevsky,&nbsp;I. V. Kulakov","doi":"10.1134/S1068162025600473","DOIUrl":"10.1134/S1068162025600473","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Objective:&lt;/b&gt; The aim of this work was to synthesize a new amide derivative of betulinic acid—&lt;i&gt;N&lt;/i&gt;-[1-(1-adamantyl)ethyl]-3-hydroxylup-20(29)-en-28-amide, containing in the structure the pharmacophoric 1-(1-adamantyl)ethylamine group (active substance of the antiviral drug Rimantadine) and to evaluate its antiviral action &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;. &lt;b&gt;Methods:&lt;/b&gt; modification of betulinic acid was carried out by the interaction of betulinic acid with 1-(adamantan-1-yl)ethan-1-amine hydrochloride through the stage of &lt;i&gt;in situ&lt;/i&gt; (without isolation) production of the corresponding betulinic acid chloride with thionyl chloride in a solution of dimethylformamide in the presence of potash. At the initial stage of the study, the antiviral activity of the drug was determined &lt;i&gt;in vitro&lt;/i&gt; in 96-well immunological plates with a freshly obtained culture of peripheral blood lymphocytes from a cow with leukemia, onto which different concentrations of the studied substance were layered in one row of wells, and rimantadine hydrochloride in another row with a dilution factor of 1 : 2 (from 1000 to 0.48 μg/mL) and subjected to 24 h incubation in a thermostat, followed by direct immunofluorescence reaction (DIF). Then an &lt;i&gt;in vivo&lt;/i&gt; experiment was conducted on agouti guinea pigs (&lt;i&gt;n&lt;/i&gt; = 25). Animals of the experimental groups (&lt;i&gt;n&lt;/i&gt; = 5) were infected intraperitoneally with a cell suspension of lymphocytes isolated from a cow sick with leukemia, and then the substance was administered subcutaneously: group 1—once 2 h before infection at a dose of 40 μg/mg; group 2—twice at the same dose (2 h before and on the 7th day after infection); group 3—three times at the same dose (2 h before and on the 7th and 14th days after inoculation of the viral suspension); Group 4 did not receive the drug (positive control). Animals of the control group (&lt;i&gt;n&lt;/i&gt; = 5) were administered physiological saline. &lt;b&gt;Results and Discussion:&lt;/b&gt; The structure of the synthesized &lt;i&gt;N&lt;/i&gt;-[1-(1-adamantyl)ethyl]-3-hydroxylup-20(29)-en-28-amide was proven using &lt;sup&gt;1&lt;/sup&gt;H, &lt;sup&gt;13&lt;/sup&gt;C NMR spectroscopy and high-resolution mass spectrometry. It was found that the minimum inhibitory dose of the substance was 31.2 μg/mL, as evidenced by the absence of specific luminescence of the antigen-antibody complex on 3–4 pluses in the &lt;i&gt;in vitro&lt;/i&gt; experiment taking into account the DIF. At the same time, rimantadine did not have an inhibitory effect on the bovine leukemia virus. Based on the results of &lt;i&gt;in vivo&lt;/i&gt; diagnostic studies in direct and indirect immunofluorescence (IIF) and PCR, it was shown that the drug demonstrated the highest anti-leukemic activity in the 2nd and 3rd groups of guinea pigs, in which after 2-3-fold administration of the test substance, positive samples were noted in only 20% of animals by the 150th day from the start of the experiment. &lt;b&gt;Conclusions:&lt;/b&gt; Based on the diagnostic studies, it can be concluded that the compound &lt;i&gt;N&lt;","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1715 - 1724"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145144874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, and Molecular Docking of Novel Fluorine-Containing 1,2,3-Triazole-tethered Pyrazole-Chalcone Derivatives as Antimicrobial Agents","authors":"M. S. Jangale,&nbsp;N. D. Bhoge,&nbsp;A. A. Pund,&nbsp;B. K. Magare","doi":"10.1134/S1068162024606323","DOIUrl":"10.1134/S1068162024606323","url":null,"abstract":"<p><b>Objective:</b> A new series of fluorine-containing 1,2,3-triazole-pyrazole-chalcone derivatives (<b>VIIIa–VIIIl</b>) was synthesized <i>via</i> Claisen–Schmidt condensation of 1,4-disubstituted 1,2,3-triazole-tethered acetophenone derivatives with 1,3-diphenyl-1<i>H</i>-pyrazole-4-carbaldehyde derivatives in the presence of the base lithium hydroxide. <b>Methods:</b> All newly synthesized compounds were characterized by ¹H, ¹³C NMR, and HR-MS spectral techniques. Antibacterial activity was evaluated <i>in vitro</i> against Gram-positive <i>Streptococcus pyogenes</i> and <i>Staphylococcus aureus</i>, and Gram-negative <i>Pseudomonas aeruginosa</i> and <i>Escherichia coli</i> strains. Antifungal activity was screened against the fungal pathogens <i>Aspergillus niger</i> and <i>Candida albicans</i>, with MIC values determined for the novel compounds. <b>Results and Discussion:</b> Compounds (<b>VIIIe</b>), (<b>VIIIf</b>), and (<b>VIIIg</b>) exhibited good antibacterial activity against all tested bacterial strains. The majority of the compounds showed excellent antifungal activity. Among them, compounds (<b>VIIIb</b>) and (<b>VIIId</b>) showed twofold better antifungal activity (MIC of 250 µg/mL) than the reference drug griseofulvin, while compounds (<b>VIIIa</b>), (<b>VIIIc</b>), (<b>VIIIg</b>), and (<b>VIIIl</b>) exhibited antifungal activity comparable to that of griseofulvin (MIC of 500 µg/mL) against <i>C. albicans</i> strains. Molecular docking studies revealed that the newly synthesized compounds exhibited favorable binding affinities. The results from molecular docking correlate well with the experimental antifungal activity. Compounds (<b>VIIIb</b>) and (<b>VIIId</b>) showed the best binding affinity scores. <b>Conclusions:</b> These superior results are attributed to the development of hybrid molecules containing 1,4-disubstituted 1,2,3-triazole, pyrazole, and chalcone scaffolds, along with fluorine substitution(s), and the combined inductive and resonance effects of the substituents. These findings from the MIC activity data provide new insights for the design of lead molecules against microbial infections.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1591 - 1604"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fabrication and Characterization of Piroxicam-Loaded Glycolated Chitosan-Stabilized Transdermal Patch","authors":"Sajid Raza,&nbsp;Muhammad Akhlaq,&nbsp;Aisha Siddiqua,&nbsp;Rukhshnda Habib,&nbsp;Khalid J. Alzahrani,&nbsp;Khalaf F. Alsharif,&nbsp;Abul Kalam Azad","doi":"10.1134/S1068162024607006","DOIUrl":"10.1134/S1068162024607006","url":null,"abstract":"<p><b>Objective:</b> The transdermal drug delivery system is designed to transport drugs into the bloodstream through the skin. <b>Methods:</b> A controlled-release transdermal patch of piroxicam was developed using glycol chitosan as a permeation enhancer to address issues related to gastric ulcers and frequent dosing. Matrix-type piroxicam patches were prepared using chitosan and glycol chitosan in various ratios to achieve controlled drug release and enhanced skin penetration. <b>Results and Discussion:</b> The prepared patches demonstrated consistent drug content, weight uniformity, folding endurance, tensile strength, and moisture uptake/loss values. A key novelty of the study is the use of glycol chitosan as a permeation enhancer, which significantly improved the bioavailability of piroxicam <i>in vivo</i>. Glycol chitosan was found to alter the protein structure of the stratum corneum and affect tight junctions in the granular layer, leading to increased water content and modification of intercellular lipids in the stratum corneum. The patches were also evaluated for stability and skin sensitivity. <i>In vitro</i> release studies using a Franz diffusion cell with rabbit skin revealed that the drug release kinetics followed a non-Fickian and zero-order model. Stability studies indicated no significant changes in patch characteristics over time. The formulation FPRXG6, which contained the highest concentration of glycol chitosan, exhibited maximum skin permeability and the highest plasma drug concentration (<i>C</i>_max = 15.87 ± 2.35 ng/mL). <b>Conclusions:</b> These findings suggest that the formulation enhances and prolongs bioavailability, maintaining plasma drug levels within the therapeutic range.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1762 - 1779"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spiro(DHPM-isatin) Derivatives: Synthesis, Nematicidal Activity, and Computational Analysis","authors":"Jashandeep Kaur,&nbsp;Divya Utreja,&nbsp;N.K. Dhillon,&nbsp;Rajesh K. Pathak,&nbsp;Harwinder Singh Buttar","doi":"10.1134/S106816202460630X","DOIUrl":"10.1134/S106816202460630X","url":null,"abstract":"<p><b>Objective:</b> Dihydropyrimidinone–isatin derivatives exhibit a wide range of biological activities, including antifungal, antibacterial, antitumor, and anticancer properties. Due to the deregistration of all existing antinemic compounds, our research group aims to identify new compounds with potent nematicidal activity. <b>Methods:</b> A one-pot nucleophilic addition of urea and a 1,3-dicarbonyl compound to the C-3 position of isatin was performed to obtain spiro(DHPM-isatin) derivatives. These were characterized using ¹H, ¹³C NMR, FT-IR spectroscopy, and mass spectrometry. The synthesized derivatives were evaluated for their ovicidal and larvicidal potential against the plant pathogen <i>Meloidogyne incognita</i>. <b>Results and Discussion:</b> The spiro(DHPM-isatin) derivative (<b>IVe</b>) exhibited significant inhibition of egg hatching, achieving 98.00% inhibition at 1500 ppm after 168 h, along with notable larvicidal activity. In contrast, derivative (<b>IVf</b>) showed exceptional efficacy, causing 100% juvenile mortality at 168 h at concentrations of 750 ppm and above, along with pronounced inhibition of egg hatching. Furthermore, <i>in silico</i> studies conducted on five <i>M. incognita</i> proteins—carboxylic ester hydrolase, cytochrome c oxidase, putative aspartate protease, ATP synthase, and cytochrome <i>b</i>—revealed that the tested derivatives (<b>IVa–IVh</b>) effectively bind to the amino acid residues Tyr, Glu, Arg, His, Ala, Asp, Ser, Asn, Leu, Lys, Phe, and Glu, which may serve as key interaction points for controlling this destructive plant pathogen. Additionally, ProTox-II analysis classified all synthesized compounds as toxicity class IV and confirmed that they satisfy Lipinski’s rule, suggesting their potential as effective agrochemical candidates. <b>Conclusions:</b> The synthesized spiro(DHPM-isatin) derivatives demonstrated significant nematicidal activity, with compound (<b>IVb</b>) emerging as the most potent, likely due to the presence of methoxy and amide functionalities. The combined <i>in vitro</i> and <i>in silico</i> findings support its potential as a safe and effective agrochemical candidate for the management of <i>M. incognita</i>.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1558 - 1570"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of New 1,4-Disubstituted 1,2,3-Triazole Hybrids: In Vitro Anti-Breast Cancer and Anti-EGFR Activity, and In Silico Molecular Docking Studies","authors":"Venu Kudapa,&nbsp;B. Saritha,&nbsp;B. B. V. Sailaja","doi":"10.1134/S1068162024607341","DOIUrl":"10.1134/S1068162024607341","url":null,"abstract":"<p><b>Objective:</b> Encouraged by previously developed 4-azaindole, thiazolidine-2,4-dione, and 1,2,3-triazole-based EGFR-targeting anti-breast cancer agents, our group aimed to design new 4-azaindole–thiazolidine-2,4-dione–1,2,3-triazole hybrids and evaluate their anti-breast cancer and anti-EGFR activities. <b>Methods:</b> As part of our ongoing work on the development of new anticancer agents, this study focused on the synthesis of hybrid molecules. The anti-breast cancer and anti-EGFR activities of the newly synthesized hybrids were assessed by IC₅₀ measurements, and molecular docking studies were conducted using AutoDock Tools. <b>Results and Discussion:</b> Compound (<b>VIIg</b>) displayed greater anti-breast cancer activity against MCF-7 and MDA-MB-231 cell lines compared to the standard drug 5-Fluorouracil (5-FU). Compounds (<b>VIIb</b>) and (<b>VIIh</b>) exhibited higher potency against MCF-7 than 5-FU. Compounds (<b>VIIb</b>) and (<b>VIIg</b>) showed significant EGFR inhibition relative to the standard drug Erlotinib. Furthermore, compounds (<b>VIIb</b>), (<b>VIIg</b>), and (<b>VIIh</b>) demonstrated better binding energies and inhibition constants for EGFR (PDB ID: 4HJO) than Erlotinib. <b>Conclusions:</b> Compounds (<b>VIIb</b>), (<b>VIIg</b>), and (<b>VIIh</b>) exhibited potent anti-breast cancer activity, which was supported by their strong anti-EGFR activity.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1789 - 1800"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phenol-Free Method for the Robust Isolation of the Double-Stranded RNA Produced in the E. coli HT115 Strain","authors":"A. A. Ivanov,&nbsp;T. S. Golubeva","doi":"10.1134/S1068162024607067","DOIUrl":"10.1134/S1068162024607067","url":null,"abstract":"<p><b>Objective:</b> Different variants of phenol-chloroform nucleic acid extraction are widely used for double-stranded RNA isolation following its production in <i>E. coli</i>. All existing protocols require phenol, which is hazardous to the environment, and further clean-up steps to concentrate and purify the target molecule before it can be used in experiments. Aiming to develop an economical phenol-free method with high target dsRNA yield and no need for additional clean-up steps, we substituted phenol with methanol and incorporated DNA hydrolysis into the isolation pipeline. <b>Methods:</b> DNA hydrolysis following thermal lysis of bacteria was performed prior to the main extraction step. Methanol-chloroform phase separation was used to separate the target RNA from proteins. A PEG-8000 precipitation step allowed precipitation of high molecular weight RNA only. <b>Results and Discussion:</b> We found that methanol could be used instead of phenol and that some traditional purification techniques could be incorporated into the cell lysis and nucleic acid precipitation steps, allowing extraction of RNA with up to 25% target dsRNA content. Given the high and reproducible target molecule content, the dsRNA thus obtained may be used directly or further processed to remove unwanted RNA. However, no published method suggests a purification approach for achieving 100% target molecule content. <b>Conclusions:</b> The proposed method facilitates double-stranded RNA isolation from <i>E. coli</i> culture without requiring phenol or expensive reagents. Consistently high content of the target molecule can be achieved, in contrast to phenol-chloroform extraction where additional clean-up steps are required. The application of this methodology will be beneficial in laboratories engaged in fundamental or applied research on RNA interference. However, scaling the technology for agricultural use may require adjustments to the protocol described in this work.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1521 - 1528"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, and Biological Evaluation of Novel EZH2 Inhibitors","authors":"Dan Wang,&nbsp;Ming-Tao Xia,&nbsp;Xiang Li,&nbsp;Ru-Xing Wang,&nbsp;Ling Yu,&nbsp;Shuai Li","doi":"10.1134/S1068162024606037","DOIUrl":"10.1134/S1068162024606037","url":null,"abstract":"<p><b>Objective:</b> Many studies have reported that EZH2 is a promising anti-tumor target. <b>Methods:</b> The target compounds were synthesized through multi-step reactions involving amide coupling and palladium-catalyzed cross-coupling, with structures confirmed by HR-ESI-MS and ¹H, ¹³C NMR spectroscopy. Biological evaluations included <i>in vitro</i> cell viability assays (CCK-8), EZH2 enzyme inhibition assays, molecular docking studies, and ADMET property predictions to assess pharmacokinetic profiles. <b>Results and Discussion:</b> In this study, four small-molecule inhibitors targeting EZH2 were designed and synthesized, using loureirin C as the lead compound. The results of the CCK-8 assay showed that compound (<b>DD1</b>) had a stronger inhibitory effect on the viability of A375 cells. In addition, compound (<b>DD1</b>) exhibited an <i>in vitro</i> enzyme inhibitory effect comparable to that of tazemetostat. Molecular docking studies demonstrated that compound (<b>DD1</b>) could enter the active site and interact with key amino acid residues. Pharmacokinetic prediction indicated that compound (<b>DD1</b>) had favorable biological activity, with relative index values comparable to those of positive control drugs. <b>Conclusions:</b> In summary, we have successfully synthesized a series of EZH2 inhibitors that are expected to represent an attractive therapeutic strategy for tumors.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1498 - 1505"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145144827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzymatic Synthesis and Molecular Docking Studies of Substituted 5-Phenyl-1,2,4-triazole-3-thione Deoxyribosides","authors":"I. V. Fateev,&nbsp;S. A. Sasmakov,&nbsp;A. A. Ziyaev,&nbsp;Zh. M. Abdurakhmanov,&nbsp;T. T. Toshmurodov,&nbsp;S. A. Ikramov,&nbsp;N. A. Tosheva,&nbsp;V. D. Frolova,&nbsp;E. A. Zorina,&nbsp;E. A. Zayats,&nbsp;B. Z. Eletskaya,&nbsp;O. S. Smirnova,&nbsp;M. Ya. Berzina,&nbsp;A. O. Arnautova,&nbsp;Yu. A. Abramchik,&nbsp;M. A. Kostromina,&nbsp;A. L. Kayushin,&nbsp;K. V. Antonov,&nbsp;I. A. Prokhorenko,&nbsp;A. S. Paramonov,&nbsp;V. L. Аndronova,&nbsp;R. S. Esipov,&nbsp;Sh. S. Azimova,&nbsp;A. I. Miroshnikov,&nbsp;I. D. Konstantinova","doi":"10.1134/S1068162025602125","DOIUrl":"10.1134/S1068162025602125","url":null,"abstract":"<p><b>Objective:</b> Derivatives of 1,2,4-triazole are very important in the pharmaceutical industry. Some drugs, including nucleoside analog ribavirin, are available in clinical therapy. However, ribavirin has a number of significant drawbacks, prompting the search for compounds with a more favorable therapeutic index among its structural counterparts. In this study, we synthesized several derivatives of 5-phenyl-1,2,4-triazole-3-thione and enzymatically glycosylated them into 2-deoxyribosides. Molecular docking was used to investigate how a triazole with two hydrophobic substituents could bind to the active site of <i>E. coli</i> purine nucleoside phosphorylase. <b>Methods:</b> The process involves the synthesis of α-<i>D</i>-ribose-1-phosphate from uridine by <i>E. coli</i> uridine phosphorylase (UP). The resulting α-<i>D</i>-ribose-1-phosphate and heterocyclic compound underwent enzymatic glycosylation by <i>E. coli</i> purine nucleoside phosphorylase (PNP) to produce the desired product. <b>Results and Discussion:</b> Previously synthesized 5-phenyl-1,2,4-triazole-3-thione (<b>I</b>) was reacted with alkyl iodide or alkyl bromide in the presence of potassium carbonate in dry acetone. In this way, methyl, ethyl, and propyl derivatives were synthesized. All the compounds were substrates for <i>E. coli</i> purine nucleoside phosphorylase, so enzymatic synthesis of their deoxyribosides was performed. Subsequently, compounds (<b>I</b>–<b>IV</b>) were docked using the SwissDock web service. The Attracting Cavities docking algorithm and the <i>E. coli</i> PNP protein model with 7-deazahypoxanthine and sulfate as ligands (PDB 5IU6) were used. The antiherpetic activity of the synthesized bases and nucleosides was investigated. <b>Conclusions:</b> New 5-phenyl-1,2,4-triazole-3-thione 2-deoxyribosides with bulky substituents at position 3 were synthesized using an enzymatic transglycosylation reaction. A molecular docking study of the 1,2,4-triazole derivatives with two hydrophobic substituents suggested possible modes of their binding to the active site of <i>E. coli</i> purine nucleoside phosphorylase. Both cytotoxicity towards <i>Vero E6</i> cells and antiviral activity increase with increasing length of the substituent at position 3 in 1,2,4-triazole.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1780 - 1788"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Catalytic Optimization of Quinoline–Pyridine Hybrids as New Mannich Bases: An Effective Structural Motif in the Treatment of Tuberculosis","authors":"Heta B. Vasveliya,&nbsp;Jignesh H. Pandya,&nbsp;Hinaben K. Tilavat,&nbsp;Amita J. Jivani","doi":"10.1134/S1068162024606712","DOIUrl":"10.1134/S1068162024606712","url":null,"abstract":"<p><b>Objective:</b> The molecular structure of quinoline–pyridine hybrids suggests their potential as therapeutic agents, particularly for the treatment of tuberculosis, due to their notable biological activity. In light of the increasing prevalence of drug-resistant strains of <i>Mycobacterium tuberculosis</i>, our research focuses on the development of novel compounds with enhanced antitubercular efficacy. <b>Methods:</b> As part of our ongoing efforts to identify effective antitubercular agents, we synthesized quinoline–pyridine hybrids <i>via</i> a one-pot Mannich reaction, employing 3-aminoquinoline, aryl aldehydes, and 3-acetylpyridine in the presence of zirconium(IV) chloride (ZrCl₄) as a catalyst. Various Lewis acids, Brønsted acids, and organocatalysts were evaluated to optimize the yield of the target compounds. The synthesized molecules were characterized using ¹H, ¹³C NMR, IR, and mass spectrometry. <b>Results and Discussion:</b> Among the synthesized compounds, (<b>IVb</b>) (bearing a 2-chloro substituent), (<b>IVf</b>) (with 2,4-dichloro substituents), and (<b>IVg</b>) (bearing a 4-nitro group) exhibited moderate antitubercular activity, with minimum inhibitory concentrations (MIC) of 12.5 µg/mL against <i>M. tuberculosis</i> H37Rv. These compounds showed promising efficacy in comparison to standard antitubercular drugs such as isoniazid, rifampicin, and ethambutol. The findings indicate that the presence of electron-withdrawing groups, such as chloro and nitro substituents, enhances the compounds’ activity against the pathogen. <b>Conclusions:</b> The quinoline–pyridine Mannich bases synthesized in this study represent a promising scaffold for the development of novel antitubercular agents. The increased efficacy of selected derivatives highlights their potential for further development as therapeutic candidates in tuberculosis treatment.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 4","pages":"1752 - 1761"},"PeriodicalIF":1.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145145392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}