Russian Journal of Bioorganic Chemistry最新文献

{"title":"Single-Domain Nanobodies for Determination of Conformational Changes in Transferrin and Their Use in Fluorescent Polarization Immunoassay","authors":"L. I. Mukhametova,&nbsp;S. A. Eremin,&nbsp;I. V. Mikhura,&nbsp;O. S. Goryainova,&nbsp;A. M. Sachko,&nbsp;T. I. Ivanova,&nbsp;S. V. Tillib","doi":"10.1134/S1068162024605470","DOIUrl":"10.1134/S1068162024605470","url":null,"abstract":"<p><b>Objective: </b>Transferrin (Tf) exists in two forms in blood plasma: iron-containing holo-Tf and iron-free apo-Tf forms. An important biochemical marker of diseases associated with iron deficiency or excess is the quantitative ratio of these forms in human blood plasma. <b>Methods</b>: Application of the fluorescence polarization immunoassay (FPIA) method and the use of recombinant camel nanobodies as a recognition reagent for the rapid determination of holo-Tf and apo-Tf will allow the development of a rapid method for determining two transferrin conformations. <b>Results and Discussion:</b> Conjugates of camel nanobodies aTf1 and aTf2 to holo- and apo-forms of human transferrin (Tf) with fluorescein isothiocyanate (FITC) were synthesized and characterized. Concentrations of FITC-aTf1 and FITC-aTf2 conjugates (2.5–5 nM) with an optimal signal-to-noise ratio were selected and the binding kinetics of the resulting FITC-aTf1 and FITC-aTf2 conjugates to holo- and apo-Tf was studied using the fluorescence polarization method. It was shown that complete binding of FITC-aTf1 and FITC-aTf2 conjugates to holo- and apo-Tf is observed after 15 and 5 min of incubation, respectively. The equilibrium dissociation constants of FITC-aTf1*holo-Tf and FITC-aTf2*apo-Tf complexes were determined to be 30.7 ± 0.3 and 15.3 ± 0.2 nM, respectively. It was demonstrated that incubation of FITC-aTf1 and FITC-aTf2 conjugates with other human proteins—lactoferrin, serum albumin and lysozyme did not change the fluorescence polarization signal, indicating high specificity of the assay. It was shown that the FITC-aTf1/apo-Tf and FITC-aTf2/holo-Tf reagent pairs also did not exhibit binding to each other, confirming the affinity of FITC-aTf1 and FITC-aTf2 conjugates to holo- and apo-Tf, respectively. <b>Conclusions:</b> This work demonstrates the possibility of determining two forms of transferrin in human physiological fluids using the FPIA method, which may have diagnostic value, and the use of a portable fluorescence analyzer will allow this analysis to be carried out outside the walls of specialized laboratories.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 2","pages":"702 - 711"},"PeriodicalIF":1.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S1068162024605470.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of Some Thieno[2,3-b]pyridines, Thieno[3,2-d]pyrimidinones, and Thieno[3,2-d][1,2,3]triazinones as Insecticidal Agents Against Aonidiella aurantii","authors":"Etify A. Bakhite,&nbsp;Mohamed A. Gad,&nbsp;Esraa Khamies,&nbsp;Felwa A. Thagfan,&nbsp;Rania Ali El Hadi Mohamed,&nbsp;Moustafa M. S. Bakry","doi":"10.1134/S1068162024605512","DOIUrl":"10.1134/S1068162024605512","url":null,"abstract":"<p><b>Objective: </b><i>Aonidiella aurantii</i>, a highly polyphagous insect pest belonging to the Diaspididae family, is particularly harmful to citrus plants. This pest poses a significant threat to citrus production by infesting both fruits and foliage. In contrast, heterocycle-based compounds have proven to be essential in agrochemicals and pesticides, including fungicides, insecticides/acaricides, and herbicides. In light of this, our research group focused on the synthesis of the title compounds and the evaluation of their insecticidal activity against <i>Aonidiella aurantii</i>. <b>Methods:</b> Three main series of fused heterocyclic compounds, predominantly featuring the ethyl nicotinate scaffold as a substructure, were synthesized in our laboratory. Most of the synthesized compounds were evaluated for their insecticidal activity against the nymphs and adult females of <i>Aonidiella aurantii</i> using the guava leaf dipping technique. <b>Results and Discussion:</b> The reaction of ethyl 4-aryl-5-cyano-2-methyl-6-thioxo-1,6-dihydropyridine-3-carboxylates (<b>Ia–Ib</b>) with <i>N</i>-aryl-2-chloroacetamides, carried out by refluxing in ethanol with a slight excess of anhydrous sodium carbonate, resulted in the formation of the corresponding 3-amino-4-aryl-2-[<i>N</i>-(aryl)carbamoyl]-5-ethoxycarbonyl-6-methylthieno[2,3-<i>b</i>]pyridines (<b>IIa–IIe</b>) in excellent yields. Upon boiling compounds (<b>IIb–IId</b>) with triethyl orthoformate in the presence of acetic anhydride, pyrido[3',2':4,5]thieno[3,2-d]pyrimidinones (<b>IIIb–IIId</b>) were obtained. Treatment of compounds (<b>IIa–IId</b>) with a concentrated solution of sodium nitrite in glacial acetic acid resulted in the formation of pyrido[3',2':4,5]thieno[3,2-<i>d</i>][1,2,3]triazinones (<b>IVa–IVd</b>). The structures of all compounds were confirmed through elemental and spectral analyses. <b>Conclusions:</b> Compounds containing the 4-chlorophenyl scaffold, such as (<b>Ib</b>) and (<b>IIId</b>), exhibited promising results against both nymphs and adult females of <i>Aonidiella aurantii</i>.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 2","pages":"816 - 826"},"PeriodicalIF":1.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786358","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":"Exploring Synthesis, DFT Characterization, and Molecular Docking of β-Naphthol Derivatives: Investigating Dual Enzyme Inhibition and Antimicrobial Potential with ADMET Profiling","authors":"Janaki H. Chauhan,&nbsp;Bhavesh L. Dodiya,&nbsp;Haresh K. Ram","doi":"10.1134/S1068162024604671","DOIUrl":"10.1134/S1068162024604671","url":null,"abstract":"<p><b>Objective:</b> This study aims to design, synthesize, and evaluate novel compounds for the inhibition of α-amylase and α-glucosidase enzymes, with potential applications in enzyme inhibition and antimicrobial therapy. A multidisciplinary approach was employed, integrating molecular docking, <i>in vitro</i> inhibitory assays, and Density Functional Theory (DFT) analysis. <b>Methods:</b> A series of compounds were synthesized and characterized using NMR, IR spectroscopy, and mass spectrometry. Structural modifications were made to enhance enzyme inhibition. Molecular docking, <i>in vitro</i> assays, and structure-activity relationship (SAR) analysis were conducted to assess the relationship between structure and inhibitory activity. <b>Results and Discussion:</b> Molecular docking and SAR analysis revealed that a 3-chloro substituted compound exhibited the strongest inhibition of α-amylase, while a 2-bromo substituted compound was identified as the most potent inhibitor of α-glucosidase. These findings were confirmed by <i>in vitro</i> assays. DFT analysis supported the stability and reactivity of the compounds, and ADME profiling indicated favorable pharmacokinetic properties. <b>Conclusions:</b> This study identified two promising enzyme inhibitors, providing insights for the development of novel therapeutic agents targeting enzyme-related diseases.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 2","pages":"642 - 672"},"PeriodicalIF":1.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786537","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":"Ultrasound-Assisted Synthesis of Polyfunctionalized Pyridine Derivatives Catalyzed by Silica-Supported Perchloric Acid: In Vitro Anticancer Studies and Molecular Docking","authors":"N. Hussain Basha,&nbsp;T. Jagadish,&nbsp;P. Karthikeyan,&nbsp;Krishnakumar Balu,&nbsp;Mani Durai,&nbsp;Mohd Afzal,&nbsp;Young-Ho Ahn,&nbsp;M. Pasupathi,&nbsp;K. Venkatesan","doi":"10.1134/S1068162024606451","DOIUrl":"10.1134/S1068162024606451","url":null,"abstract":"<p><b>Objective:</b> To synthesize polyfunctionalized pyridine derivatives <i>via</i> a four-component reaction involving 1-tetralone, malononitrile, aldehydes, and ammonium acetate, catalyzed by silica-supported perchloric acid under ultrasound irradiation and conventional methods. <b>Methods:</b> The sonochemical method offers several advantages, including a cleaner reaction profile, an inexpensive catalyst, mild reaction conditions, rapid reaction times, high yields, catalyst reusability, and straightforward experimental and work-up procedures. <b>Results and Discussion:</b> The structures of all pyridine derivatives were confirmed using various characterization techniques, including IR, ¹H and ¹³C NMR spectroscopy, and mass spectrometry. The synthesized derivatives were evaluated for their anticancer potential through molecular docking studies against CSF1R and EGFR inhibitors. The results indicated that compounds (<b>IVb</b>) and (<b>IVj</b>) exhibited the most favorable binding energies, while compound (<b>IVg</b>) formed the highest number of hydrogen bonds with the EGFR protein. <b>Conclusions:</b> This study presents a simple and eco-friendly approach for synthesizing 2-amino-3-cyanopyridine derivatives using both conventional and ultrasonic techniques, with silica-supported perchloric acid as a reusable catalyst. According to docking studies, all derivatives exhibited stronger interactions with EGFR than with CSF1R. Furthermore, the anticancer activity of the synthesized compounds was assessed against MCF-7 cancer cell lines using the MTT assay. Compounds (<b>IVd</b>) and (<b>IVj</b>) demonstrated the highest anticancer activity.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 2","pages":"932 - 946"},"PeriodicalIF":1.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786360","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":"Pyran-Fused Analogues and Their Potential Applications","authors":"Sumit Kumar,&nbsp;Aditi Arora,&nbsp;Sandeep Kumar,&nbsp;Rajesh Kumar,&nbsp;Nihar Nalini Senapati,&nbsp;Brajendra K. Singh","doi":"10.1134/S1068162024606001","DOIUrl":"10.1134/S1068162024606001","url":null,"abstract":"<p>Heterocyclic compounds represent one of the most prominent classes of currently used pharmaceuticals. Among these, the pyran ring has attracted significant research interest due to its broad spectrum of pharmacological properties. Notably, molecules such as benzopyrans, chromones, flavonoids, coumarins, xanthones, and naphthoquinones—each featuring a pyran core—exhibit diverse biological activities. This structural motif is widely present in both naturally occurring and synthetically derived compounds. The remarkable medicinal properties of various natural products, including pyrans and benzopyrans, have captivated the scientific community. This report provides a concise overview of the synthesis, characterization, and therapeutic applications of pyran-fused analogues.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 2","pages":"373 - 438"},"PeriodicalIF":1.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786536","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":"Platinum Polyoxoniobate: Stability, Cytotoxicity, and Cellular Uptake","authors":"A. V. Yudkina,&nbsp;I. P. Vokhtantsev,&nbsp;D. A. Rychkov,&nbsp;V. V. Volchek,&nbsp;P. A. Abramov,&nbsp;M. N. Sokolov,&nbsp;D. O. Zharkov","doi":"10.1134/S1068162024606141","DOIUrl":"10.1134/S1068162024606141","url":null,"abstract":"<p><b>Objective: </b>Platinum polyoxometalates are Pt (IV) complexes containing bulky cluster ligands. We have shown previously that platinum polyoxoniobate [(Nb₆O₁₉)₂{Pt(OH)₂}₂]¹²⁻ (Pt-PON1) containing two Pt centers can covalently bind DNA. Here we have addressed the structural stability of Pt-PON1 and its conjugate with guanine at the N7 position, cytotoxicity of this compound, and its accumulation in living cells. <b>Methods:</b> Quantum mechanical modeling was used to estimate the stability of Pt–guanine bond. Cytotoxicity of Pt-PON1 was evaluated by incubating various concentrations of the compound with cultured human and Escherichia coli cells, and the levels of intracellular Pt-PON1, by atomic emission spectroscopy. <b>Results and Discussion:</b> Calculations show that the Pt-PON1 complex is unstable outside the crystal lattice, while its conjugate with guanine likely undergoes structural rearrangement quite easily. A decrease in the survival of <i>E. coli</i> XL1-Blue and DH5α strains and human HEK293T and MCF-7 cell lines was observed already at 20 μM Pt-PON1 but at higher concentrations the compound was poorly soluble in biologically compatible media. The measured levels of intracellular Pt and Nb suggest that Pt-PON1 is efficiently taken up by human cells in a stoichiometry corresponding to the original complex. <b>Conclusions:</b> Platinum polyoxometalates, provided their solubility can be improved, may be considered as promising antitumor agents.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 2","pages":"693 - 701"},"PeriodicalIF":1.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786616","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":"Comprehensive Review and Perspective on Fructose 1,6-Bisphosphatase Inhibitors for the Management of Type 2 Diabetes Mellitus","authors":"Sanjay D. Sawant,&nbsp;Vasundhara N. Sawant","doi":"10.1134/S1068162024605299","DOIUrl":"10.1134/S1068162024605299","url":null,"abstract":"<p>The worldwide increasing prevalence of type 2 diabetes emphasizes the need to explore safer and more effective anti-hyperglycemic agents. Type 2 diabetes mellitus (T2DM) is characterized by excessive gluconeogenesis and the resulting endogenous glucose production. Currently used hypoglycemic agents do not act through direct inhibition of gluconeogenesis-mediated glucose production. Recently, fructose 1,6-bisphosphatase (FBPase) has emerged as a promising target to control the overproduction of glucose from gluconeogenesis, as it is a key enzyme in the middle cycle of gluconeogenesis. Several studies on FBPase inhibitors for the management of T2DM have notably shown no severe hypoglycemia, weight gain, or other serious side effects. In the present article, the authors summarize recent developments in the field of FBPase inhibitors with insights into glucose homeostasis, gluconeogenesis, mechanisms of currently available drugs, and emerging targets for the management of T2DM. Further, some strategies and structure-activity relationships (SARs) of FBPase inhibitors are discussed. This review is expected to be useful for researchers working in this area. FBPase inhibitors represent an attractive target for developing more effective and safer therapies for the treatment of T2DM and cancer. AMP mimetic inhibitors have been shown to possess an unfavorable pharmacokinetic profile; hence, efforts are required to develop covalent-allosteric, non-phosphorous-based, or natural FBPase inhibitors in the future.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 2","pages":"439 - 464"},"PeriodicalIF":1.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786534","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 Anti-Alzheimer Activity of 2,5-Disubstituted 1,3,4-Thiadiazole: Kinetic Studies, Molecular Docking, and MD Simulations","authors":"M. L. Sujatha,&nbsp;Prabhu Jalihal,&nbsp;Manjunatha S. Katagi,&nbsp;Durgesh Paresh Bidye,&nbsp;Sheshagiri R. Dixit,&nbsp;B. P. Nandeshwarappa","doi":"10.1134/S1068162024605858","DOIUrl":"10.1134/S1068162024605858","url":null,"abstract":"<p><b>Objective:</b> This study aims to design a small library of novel 2,5-disubstituted 1,3,4-thiadiazole derivatives and evaluate their antioxidant and acetylcholinesterase (AChE) inhibitory activities. <b>Methods:</b> A series of 2,5-disubstituted 1,3,4-thiadiazole derivatives were designed, synthesized <i>via</i> a convenient synthetic route, and assessed for their AChE inhibitory activity against electric eel AChE using Ellman’s method. Their antioxidant potential was evaluated <i>via</i> the DPPH free radical scavenging assay. The structures of the synthesized compounds were characterized using FT-IR, ¹H, ¹³C NMR spectroscopy, mass spectrometry, and elemental analysis. Molecular docking and molecular dynamics (MD) simulations were performed to identify potential AChE inhibitors. <b>Results and Discussion:</b> The results demonstrated that compounds (<b>IVe</b>), (<b>IVj</b>), and (<b>IVg</b>) exhibited significant antioxidant activity at 100 µg/mL compared to the reference standard. The AChE inhibition assay revealed that compounds (<b>IVe</b>), (<b>IVj</b>), (<b>IVg</b>), and (<b>IVc</b>) displayed potent inhibitory effects at a concentration of 0.004 M. Kinetic studies elucidated the mode of enzyme inhibition, showing that compound (<b>IVe</b>) exhibited a mixed-type inhibition mechanism, similar to Donepezil. Docking studies predicted moderate to strong binding affinities for all synthesized compounds (<b>IVa–IVj</b>) compared to the reference drug. Among them, compound (<b>IVe</b>) demonstrated the lowest docking energy (–10.549 kcal/mol), suggesting the highest anticholinesterase activity. MD simulations further confirmed the stable binding interactions of compound (<b>IVe</b>) within the active site of AChE. <b>Conclusions:</b> These findings suggest that compound (<b>IVe</b>) is a promising lead structure for the development of novel AChE inhibitors for the treatment of Alzheimer’s disease (AD).</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 2","pages":"912 - 931"},"PeriodicalIF":1.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786428","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 of Biologically Active 5-Substituted Analogues of 2ʹ-Deoxyuridine by Lactobacillus leichmannii Nucleoside Deoxyribosyltransferase Type II","authors":"C. S. Alexeev,&nbsp;A. M. Sergievskaia,&nbsp;D. A. Platov,&nbsp;M. S. Drenichev","doi":"10.1134/S106816202460569X","DOIUrl":"10.1134/S106816202460569X","url":null,"abstract":"<p><b>Objective:</b> NDTs and NPs, belong to the class of glycosyltransferases, which can be used to produce biologically active nucleosides by enzymatic transglycosylation under mild conditions, following the principles of ‘green chemistry’. Enzymatic transglycosylation is a stereo- and regiospecific reaction that allows obtaining target nucleosides of high purity, allowing it to compete with chemical methods of synthesis. <b>Methods:</b> In the present work, we used <i>Lactobacillus leichmannii</i> nucleoside deoxyribosyltransferase type II for the synthesis by enzymatic transglycosylation. Reaction media contained 7-methyl-2′-deoxyguanosine as a carbohydrate moiety donor, and corresponding modified pyrimidine heterocyclic bases as acceptors. <b>Results and Discussion:</b> The reaction conditions were 1 : 3 acceptor/donor molar concentration ratio and enzymatic transglycosylation was carried out in 25 mM HEPES buffer (pH 7.4). In the case of 5-CF₃-Ura and 5-Vin-Ura, the rate of formation of the target nucleoside was lower. Due to the broader substrate specificity of NDT II, we obtained 5-CF₃-dUrd, which could not be synthesized using <i>E. coli</i> TP. The yields (conversion) for 5-F-Ura, 5-Cl-Ura and 5-I-Ura were quantitative, 68% for 5-Vin-Ura and 67% for 5-CF₃-Ura. <b>Conclusions:</b> Biologically active 2ʹ-deoxyuridine derivatives in high yields were obtained, three ones currently used in clinical practice in antiviral and antitumour therapy. The selected enzyme-catalyst, initial ratios of molar concentrations of substrates and the selected nucleoside-donor – source of carbohydrate residue – will make it possible to develop environmentally friendly biochemical methods for the preparation of practically important modified nucleosides.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 2","pages":"860 - 868"},"PeriodicalIF":1.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786429","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, Docking Study, and Structural Characterization of New Bioactive Thiazolidine-4-one Derivatives as Antibacterial and Antioxidant Agents","authors":"Zainab Y. Kadhim,&nbsp;Hasanain Gomhor J. Alqaraghuli","doi":"10.1134/S1068162024605007","DOIUrl":"10.1134/S1068162024605007","url":null,"abstract":"<p><b>Objective:</b> This study involved the design and synthesis of new thiazolidine-4-one derivatives, as well as testing their antioxidant activity and evaluating their potential as antibacterial agents. <b>Methods:</b> Thiazolidine-4-one compounds (<b>T-1</b>) and (<b>T-2</b>) were synthesized by reacting 2-mercaptoacetic acid with the synthesized imines, (<b>Im-1</b>) and (<b>Im-2</b>), respectively. The synthesized compounds were characterized by physicochemical and spectrophotometric data (UV-Vis, FT-IR, ¹H, ¹³C NMR, and CHN analysis). <i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>), <i>Staphylococcus aureus</i> (<i>S. aureus</i>), and <i>Escherichia coli</i> (<i>E. coli</i>) were used as test organisms for the antibacterial activity of (T-1) and (T-2). Molecular docking experiments were performed to gain an understanding of the affinity and interaction between thiazolidine-4-one molecules and glucosamine-6-phosphate synthase (GA6PS). Hemolysis assays and DPPH^·/ABTS^·+ scavenging activity of (<b>T-1</b>) and (<b>T-2</b>) were studied. <b>Results and Discussion:</b> The results showed strong antibacterial activity of (<b>T-2</b>) compared to ciprofloxacin as a standard in inhibiting the growth of <i>P. aeruginosa</i> and <i>E. coli</i>, while its antibacterial effect in inhibiting the growth of <i>S. aureus</i> was stronger than ciprofloxacin. The data obtained from the docking studies were in perfect agreement with the data from the <i>in vitro</i> antibacterial test. Compound (<b>T-2</b>) showed good binding affinity to GA6PS, which is an important enzyme for bacterial cell wall synthesis, making (<b>T-2</b>) a promising antibacterial agent. The thiazolidine-4-ones (<b>T-1</b>) and (<b>T-2</b>) showed strong antioxidant activity, and non-toxicity was confirmed by the hemolysis method. <b>Conclusions:</b> We propose that one of the mechanisms behind the antibacterial activity of the synthesized thiazolidin-4-ones is the disruption of bacterial cytoplasmic membrane integrity, and therefore, these compounds have favorable properties for potential biomedical applications and positive future prospects.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"51 2","pages":"729 - 742"},"PeriodicalIF":1.1,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786460","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}