Russian Journal of Bioorganic Chemistry最新文献

{"title":"Special Issue Dedicated to the 75th Anniversary of the Birth of an Outstanding Soviet/Russian Scientist, one of the Founders of Russian Structural Biology, Prof. Alexander Sergeevich Arseniev (1951–2025)","authors":"Kurt Wüthrich","doi":"10.1134/S1068162026602016","DOIUrl":"10.1134/S1068162026602016","url":null,"abstract":"","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147938238","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":"Development of Mutant C120S Neuroglobin, Its Characteristics and Interaction with Cytochrome c","authors":"M. A. Semenova,&nbsp;R. G. Atrikhalov,&nbsp;O. M. Smirnova,&nbsp;V. V. Britikov,&nbsp;E. V. Britikova,&nbsp;A. A. Ignatova,&nbsp;Y. V. Bershatsky,&nbsp;A. P. Khodnenko,&nbsp;I. P. Oleynikov,&nbsp;S. A. Siletsky,&nbsp;T. V. Vygodina,&nbsp;E. V. Bocharov,&nbsp;M. P. Kirpichnikov,&nbsp;D. A. Dolgikh,&nbsp;R. V. Chertkova","doi":"10.1134/S1068162026601321","DOIUrl":"10.1134/S1068162026601321","url":null,"abstract":"<p><b>Objective:</b> The main aim of this work was the development of mutant Ngb C120S, including the production of a ¹⁵N-labeled form and its characterization using CD and NMR spectroscopy. Furthermore, we studied the redox reaction between Ngb C120S and Cyt <i>c</i> using stopped-flow spectroscopy. <b>Methods:</b> The C120S mutation was introduced into the <i>NGB</i> gene by site-directed mutagenesis. Recombinant wild-type (WT) and C120S Ngb were expressed in <i>Eschericia</i> <i>coli</i> under both rich and minimal (M9) media conditions, the latter for ¹⁵N-labeling. Proteins were purified using a combination of ammonium sulfate precipitation, anion-exchange, and size-exclusion chromatography. Structural and conformational properties were assessed by UV-visible absorption spectroscopy, circular dichroism (CD) spectroscopy, and heteronuclear NMR spectroscopy (¹H and ¹H–¹⁵N HSQC). The kinetics of electron transfer between ferrous Ngb (WT or C120S) and ferric Cyt <i>c</i> were investigated by stopped-flow spectroscopy. <b>Results and Discussion:</b> The C120S mutant was successfully produced with yields and purity comparable to WT Ngb. UV-visible and CD spectra revealed only minor differences between the mutant and WT, indicating that the mutation does not disrupt the overall fold or the heme environment. NMR analysis confirmed that the overall structure and heme hexacoordination were preserved in the mutant. A downfield shift was observed for the 3-CH₃ signal for the mutant, as well as significant perturbations in the chemical shifts of approximately 20 cross-peaks, which may be due to minor local rearrangements of hydrogen bonds and/or the chemical environment of neighboring residues at position 120. Stopped-flow kinetic measurements demonstrated that the C120S mutation did not significantly impair electron transfer. <b>Conclusions:</b> The introduction of the C120S mutation has a minor local effect on the physicochemical and structural characteristics of neuroglobin, as well as its interaction with the protein partner, cytochrome <i>c</i>. The mutant neuroglobin will be used to study the structural and dynamic characteristics of the proposed neuroglobin-cytochrome <i>c</i> complex using NMR spectroscopy.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147938323","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":"Bicelles as a Prospective Membrane Mimetic for NMR Structural Studies of Bacteriorhodopsin","authors":"M. V. Goncharuk,&nbsp;M. A. Dubinnyi,&nbsp;O. V. Nekrasova,&nbsp;A. S. Anurieva,&nbsp;P. K. Kuzmichev,&nbsp;V. V. Chupin,&nbsp;I. S. Okhrimenko,&nbsp;V. I. Borshchevskiy,&nbsp;E. V. Bocharov,&nbsp;A. S. Arseniev,&nbsp;S. A. Goncharuk","doi":"10.1134/S1068162026601345","DOIUrl":"10.1134/S1068162026601345","url":null,"abstract":"<p><b>Objective:</b> Bacteriorhodopsin (BR) from <i>Halobacterium salinarum</i> is a model membrane protein for which the details of structural transitions during its photocycle remain unclear. NMR spectroscopy offers unique insights into these dynamic processes but requires a suitable membrane-mimicking environment and efficient isotopic labeling strategies. This study aimed to develop optimized protocols for production of isotopically labeled BR, evaluate various membrane mimetics (micelles, bicelles, nanodiscs) for NMR studies, and stated bicelles as the most promising medium for high-resolution structural analysis. <b>Methods:</b> BR was expressed in <i>E. coli</i> BL21(DE3) as a Mistic fusion construct. Both uniformly (¹⁵N/¹³C/²H) and selectively (¹⁵N-Ala, ¹⁵N-Val, ¹⁵N-Leu) labeled proteins were produced using M9 minimal medium. Purification involved immobilized metal affinity and size-exclusion chromatography, followed by refolding into different membrane mimetics. Protein stability was assessed by UV–Vis spectroscopy (<i>A</i>₂₈₀/<i>A</i>₅₅₄ ratio) and by color retention. NMR spectra (¹⁵N-TROSY) were recorded at 600–800 MHz, and the numbers of signals, line widths, and rotational correlation times were compared. H/D exchange strategy and selective labeling were used to separate the signals. <b>Results and Discussion:</b> Optimized expression yielded ~40–50 mg/L of functional, isotopically labeled BR. Among all tested media, bicelles based on either CHAPS or DH₆PC provided the best combination of functional stability (maintained purple color for weeks) and spectral quality, outperforming DDM micelles and nanodiscs. Rotational correlation times for bicelles were ~30 ns, significantly smaller than those for nanodiscs (44 ns), explaining improved resolution. Negatively charged lipid (DMPG) further enhanced spectral dispersion. Selective ¹⁵N-labeling of Ala, Val, and Leu, combined with H/D exchange strategy, enabled detection of over 300 spin systems. Thus, bicelles outperform both micelles (better stability) and nanodiscs (better spectral resolution). <b>Conclusions:</b> Bicelles, based on DH₆PC and CHAPS, represent a highly promising membrane mimetic for NMR structural studies of BR. Combined with selective isotopic labeling and H/D exchange strategy, this approach enables high-quality spectra and long-term protein stability, paving the way for detailed structural and dynamic characterization of BR and related membrane proteins.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147938237","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":"Production and Structural-Functional Characterization of a Recombinant HIV-1 Env Trimer Based on the Consensus Sequence of the Most Prevalent Strains in the Russian Federation","authors":"I. A. Favorskaya,&nbsp;I. O. Ilyasov,&nbsp;I. A. Alekseeva,&nbsp;E. I. Ryabova,&nbsp;A. A. Antonova,&nbsp;D. A. Kleymenov,&nbsp;V. A. Gushchin,&nbsp;A. D. Burtseva,&nbsp;A. V. Moiseenko,&nbsp;T. S. Trifonova,&nbsp;V. O. Popov,&nbsp;N. N. Sluchanko,&nbsp;K. M. Boyko,&nbsp;D. V. Shcheblyakov,&nbsp;D. Yu. Logunov","doi":"10.1134/S1068162026601953","DOIUrl":"10.1134/S1068162026601953","url":null,"abstract":"<p><b>Objective:</b> The development of a vaccine candidate for specific active immunoprophylaxis against HIV-1 infection, based on the structure-guided design of HIV-1 Env proteins, is considered one of the most promising approaches to creating an immunogen capable of inducing broadly neutralizing antibodies (bnAbs). However, the high diversity of HIV-1 implies that immunogens based on a single specific strain may be ineffective against other circulating variants. Consequently, there is a need to develop an antigen capable of neutralizing a broad spectrum of HIV-1 genetic variants while accounting for regional strain characteristics. <b>Methods:</b> In this study, based on the sequences of Russian strains, a HIV-1 Env surface antigen and its variant with additional mutations—optimized for engagement with germline precursors of VRC01-class bnAbs—were developed and characterized. <b>Results and Discussion:</b> The CON-RUS SOSIP-v.9.3 antigen was designed based on a consensus amino acid sequence derived from the most prevalent HIV-1 variants in the Russian Federation (A6, B, CRF02_AG, and CRF63_02A6), with stabilizing SOSIP.v9.3 and TD8 mutations. The CON-RUS SOSIP-v.9.3_GT01 variant was further engineered with additional mutations to enhance binding affinity for the germline precursor of the VRC01 antibody. Biochemical characterization by BN-PAGE and SEC-MALS confirmed that both constructs predominantly form trimers with a molecular weight consistent with the expected size (~220 kDa excluding glycans). Negative-stain electron microscopy revealed that the majority of CON-RUS SOSIP-v.9.3 molecules adopt a closed conformation, as demonstrated by 2D class averaging and 3D reconstruction fitting to the closed-state BG505 SOSIP.664 structure (PDB ID: 3J5M). ELISA showed that mature VRC01 (mVRC01) binds both CON-RUS SOSIP-v.9.3 and CON-RUS SOSIP-v.9.3_GT01 with affinity comparable to reference BG505 SOSIP proteins. However, while no binding of CON-RUS SOSIP-v.9.3 to germline VRC01 (gVRC01) was detected, the GT01 modification enabled weak binding to gVRC01, although this was significantly lower than that of the BG505 SOSIP variant carrying analogous mutations. <b>Conclusions:</b> Based on the consensus sequence of HIV-1 strains prevalent in the Russian Federation, two recombinant Env constructs (CON-RUS SOSIP-v.9.3 and CON-RUS SOSIP-v.9.3_GT01) were developed, which predominantly adopt a trimeric organization and effectively engage the mature VRC01 antibody.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829647","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":"From Green Synthesis to Biological Insight: A Multifaceted Study of Dibutyl (2-amino-3-cyano-4H-chromen-4-yl)phosphonates via DFT, ADMET, Docking, and In Vitro Assays","authors":"Sumithra Poreddy,&nbsp;Mohan Gundluru,&nbsp;Surendra Pothuraju,&nbsp;Santhisudha Sarva,&nbsp;Poojitha Bellala,&nbsp;Sunitha Gundubogula,&nbsp;Jyothibabu Sajila Arya,&nbsp;Suresh Reddy Cirandur","doi":"10.1134/S1068162025602952","DOIUrl":"10.1134/S1068162025602952","url":null,"abstract":"<p><b>Objective:</b> A green, solvent-free multicomponent synthesis of dibutyl (2-amino-3-cyano-4<i>H</i>-chromen-4-yl)phosphonates was developed using a homopiperazine catalyst under ultrasound irradiation to generate multifunctional scaffolds with therapeutic potential. <b>Methods:</b> Structural stability and electronic properties of the synthesized compounds were evaluated <i>via</i> Density Functional Theory (DFT). Molecular docking was performed against EGFR, HER2, MMP-9, TGFBR1, and VEGFR2, while ADMET modeling assessed pharmacokinetic profiles and toxicity risks. Biological evaluations included antioxidant, antimicrobial, and cytotoxicity assays. <b>Results and Discussion:</b> DFT calculations confirmed molecular stability and favorable reactivity descriptors. Molecular docking revealed potent multitarget binding affinity, particularly for compounds <b>4h</b>, <b>4g</b>, and <b>4b</b>. ADMET analysis indicated promising drug-like profiles with acceptable toxicity. <i>In vitro</i> assays demonstrated potent antioxidant activity, broad-spectrum antimicrobial effects, and significant cytotoxicity against MCF-7, MDA-MB-231, DU-145, HeLa, and HepG2 cell lines. Notably, compounds <b>4h</b>, <b>4g</b>, <b>4b</b>, <b>4l</b>, and <b>4k</b> exhibited superior cytotoxic efficacy compared to doxorubicin. Observed bioactivity correlated with electronic features, including MEP distribution and frontier molecular orbital energies. <b>Conclusions:</b> The integration of green synthesis, computational modeling, and biological validation highlights these chromenyl phosphonate hybrids as promising candidates for multitarget therapeutic applications, including oncology, oxidative stress modulation, and infectious diseases.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829571","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":"Structural Studies of Bacteriorhodopsin: What Do We Know and What Did We Miss?","authors":"M. A. Dubinnyi,&nbsp;S. S. Bukhdruker,&nbsp;V. I. Borshchevskiy,&nbsp;M. V. Goncharuk,&nbsp;I. S. Okhrimenko,&nbsp;E. V. Bocharov,&nbsp;S. A. Goncharuk","doi":"10.1134/S1068162026601734","DOIUrl":"10.1134/S1068162026601734","url":null,"abstract":"<p>Bacteriorhodopsin is one of the most extensively studied membrane proteins. Since its discovery 55 years ago, thousands of papers have been published with the aim of elucidating its mechanism of action. Among these, structural biology studies are of particular importance, as they provide insight into the protein’s function at the most fundamental level. In this review, we summarize the key advances in the structural investigation of bacteriorhodopsin using the major high-resolution techniques: electron microscopy, atomic force microscopy, NMR spectroscopy, and X-ray crystallography. We also attempt to address the following questions: what data are still lacking for a complete understanding of this protein’s function, and how can each of these methods contribute to filling these gaps?</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829123","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":"Natural Neurotoxins in the Study of the Spatial Structure of Nicotinic Acetylcholine Receptors—the Main Milestones","authors":"I. E. Kasheverov,&nbsp;Yu. N. Utkin,&nbsp;V. I. Tsetlin","doi":"10.1134/S1068162026601692","DOIUrl":"10.1134/S1068162026601692","url":null,"abstract":"<p>Nicotinic acetylcholine receptors (nAChRs) belong to the superfamily of ligand-gated ion channels and are among the most studied neurotransmitter receptors. They play an important role in nerve impulse transmission in the central and peripheral nervous systems and are also involved in regulating the functions of other systems, including the immune and cardiovascular ones. This review presents the main stages of elucidating the spatial structure of nAChRs, including a detailed characterization of their ligand-binding sites using natural and synthetic neurotoxins. These stages cover, in particular, the localization of binding sites on the receptor using modified ligands, crystallographic studies of various structural homologs of the receptor, including complexes with toxins, as well as recent cryoelectron microscopy data.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829127","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":"ZHER2 Affibodies: A Versatile Platform for Diagnostics and Therapy of HER2Overexpressing Cancers","authors":"I. I. Tyuryaeva,&nbsp;E. I. Trosko,&nbsp;D. A. Luzik","doi":"10.1134/S1068162026601862","DOIUrl":"10.1134/S1068162026601862","url":null,"abstract":"<p>Overexpression of the human epidermal growth factor receptor 2 (HER2) is a well-established diagnostic and prognostic biomarker in certain malignancies and is generally associated with aggressive metastatic progression and poor clinical outcome. HER2-directed diagnostic and therapeutic strategies have achieved substantial clinical success, with monoclonal antibodies remaining the current gold standard. Nevertheless, this approach is limited by several important factors, including complex and expensive manufacturing processes and the relatively low stability of antibodies. These limitations underscore the need for alternative targeting agents. Among the most promising alternatives are affibodies, a class of small engineered proteins derived from the Z domain of staphylococcal protein A. In particular, the ZHER2 affibody family constitutes a promising group of small proteins that exhibit high affinity for the target receptor and have demonstrated success in realworld clinical applications of diagnostics and therapy of HER2overexpressing tumors. In this report, we summarize the development and optimization history of these affibodies, their structural features, advantages and limitations for clinical applications. In addition, we present our own original data highlighting the utility of ZHER2 affibodies for <i>in vitro</i> diagnostics of malignant tumors.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829125","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":"Structural Biology of Zinc-Binding Proteins and Peptides","authors":"U. V. Bulgakova,&nbsp;K. I. Balagurov,&nbsp;A. Yu. Rudenko,&nbsp;K. N. Aysin,&nbsp;S. A. Goncharuk,&nbsp;S. S. Mariasina,&nbsp;P. G. Georgiev,&nbsp;E. V. Bocharov,&nbsp;V. I. Polshakov","doi":"10.1134/S1068162026601655","DOIUrl":"10.1134/S1068162026601655","url":null,"abstract":"<p>This review systematizes current data on the structural organization, coordination chemistry, and functional roles of zinc-binding proteins and peptides. The mechanisms by which Zn²⁺ ions participate in homeostasis, enzymatic catalysis, signal transduction, and pathological processes are analyzed. A large dataset of zinc-containing protein structures deposited in the Protein Data Bank was examined. Tetrahedral coordination geometry predominates for zinc ions (over 67% of structures), with more than 92% of coordinating groups represented by residues of Cys, His, Asp, Glu, and water molecules. The most common coordination motifs are Cys₄, Cys₃His, and Cys₂His₂. Zinc ions perform both structural roles (e.g., zinc fingers, metallothioneins) and catalytic functions (including water activation and substrate polarization). The mechanisms of Zn²⁺-dependent enzymes are discussed, including carbonic anhydrases, carboxypeptidase A, superoxide dismutases, alcohol dehydrogenases, alkaline phosphatases, and matrix metalloproteinases. Zinc homeostasis systems (ZIP importers, ZnT exporters, and metallothioneins) and their regulation by transcription factors MTF-1 (in vertebrates) and ZntR (in bacteria) are described. Evidence is reviewed for the modulation of a wide range of membrane receptors by Zn²⁺ ions through multiple mechanisms, including allosteric inhibition or potentiation, stabilization of protein–protein interactions (“zinc clasps”), and ligand binding. A structural classification of zinc fingers is presented, ranging from classical CysHis₂ domains to more complex architectures containing two Zn²⁺ ions. Using the β-amyloid peptide (Aβ) as an example, the role of Zn²⁺ in pathogenic oligomerization is demonstrated, and approaches to inhibit this process are outlined. The conservation of ligand environments combined with variability in zinc coordination numbers provides a balance between rigidity and lability, enabling both structural and catalytic functions. Disruption of zinc homeostasis underlies a range of pathologies, including neurodegenerative diseases, diabetes, immune deficiency, and cancer. This review summarizes key concepts essential for further studies of Zn²⁺ ions in biological systems and for the development of therapeutic strategies based on controlling zinc-dependent biological processes.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829124","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":"Lawsone-Derived Heterocycles: Synthetic Strategies, Structure–Activity Relationships, and Therapeutic Applications","authors":"J. P. Sonawane,&nbsp;V. S. Patil,&nbsp;V. K. Suryawanshi,&nbsp;S. S. Nandre,&nbsp;P. M. Raotale,&nbsp;S. R. Patil","doi":"10.1134/S1068162025602836","DOIUrl":"10.1134/S1068162025602836","url":null,"abstract":"<p>Lawsone (2-hydroxy-1,4-naphthoquinone) has emerged as a privileged scaffold for the construction of bioactive heterocycles with applications spanning antimicrobial, antioxidant, antimalarial, anticancer, and antiplatelet therapies. This review distills advances in both classical (nucleophilic addition, cyclization) and modern (C–H activation, multicomponent, photoinduced) synthetic routes under green chemistry protocols, as well as functionalization strategies that modulate biological activity. Structure–activity relationship studies indicate that strategically incorporating lipophilic chains, aromatic groups, and heterocyclic rings improves target binding and enhances cellular potency. The growing portfolio of lawsone–metal complexes further extends therapeutic potential through dual antimicrobial and anticancer mechanisms. Despite these promising findings, comprehensive <i>in vivo</i> validation, metabolic stability, and toxicity assessments remain scarce. Future efforts should prioritize detailed SAR studies, advanced delivery platforms, and combinatorial regimens to accelerate the clinical translation of lawsone-derived drug candidates.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829126","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}