European Journal of Medicinal Chemistry Reports最新文献

{"title":"Research progress of sustained-release microsphere technology in drug delivery","authors":"Tao-Tao Ge,&nbsp;Hai-Yan Guo,&nbsp;Chun-Mei Zhang,&nbsp;Shu-Feng Li","doi":"10.1016/j.ejmcr.2025.100299","DOIUrl":"10.1016/j.ejmcr.2025.100299","url":null,"abstract":"<div><div>sustained-release microsphere technology, with its unique advantages of prolonged controlled release, enhanced therapeutic efficacy, reduced side effects, and improved patient compliance, has emerged as a research hotspot in modern drug delivery. This review systematically summarizes recent advances in sustained-release microspheres in the biomedical field. First, the core concepts and distinct advantages of this approach, compared with conventional drug administration, are elaborated. Subsequently, the principles and features of key preparation techniques, including emulsion–solvent evaporation, spray drying, and advanced microfluidic methods, are highlighted. Furthermore, the applications and validation of microsphere-based systems in diverse therapeutic areas—such as transarterial chemoembolization for cancer, chronic disease management (e.g., diabetes, psychiatric disorders), and local targeted therapies (e.g., ophthalmology, postoperative analgesia)—are critically discussed. Finally, the current challenges and future perspectives of this technology are outlined, providing insights for its further development and clinical translation.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100299"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Halogen-containing NHC and bis-NHC silver complexes. Synthesis, structure and antimicrobial activity","authors":"Alexandr S. Avksentiev ,&nbsp;Vagiz Sh Saberov ,&nbsp;Svetlana V. Shishkina ,&nbsp;Alexey B. Ryabitsky ,&nbsp;Olena Z. Komarovska-Porokhnyavets ,&nbsp;Vira I. Lubenets ,&nbsp;Vitaliy A. Matvienko ,&nbsp;Gennady F. Rayenko ,&nbsp;Liubov M. Vakhitova ,&nbsp;Nikolai I. Korotkikh","doi":"10.1016/j.ejmcr.2025.100298","DOIUrl":"10.1016/j.ejmcr.2025.100298","url":null,"abstract":"<div><div>It was found that the <em>in-situ</em> reaction of halogen-containing imidazolium and benzimidazolium salts with silver nitrate, chloride, iodide or perchlorate in the presence of potassium carbonate leads to the corresponding monocarbene (NHC) (LAgX) and bis-NHC silver complexes (L₂AgX) including the first strongly sterically shielded bis-NHC complexes (IPr)₂AgX. In the presence of o-phenanthroline, carbene-phenanthroline complex (IPr∗)(phen)AgClO₄ was obtained. The reactions can be an addition to the known method of Lin with the use of silver oxide. The halogenide silver carbene complexes are also obtained by the exchange of the anion from the ionic perchlorate complexes to halogenide ions (Cl⁻, I⁻). The structure of the synthesized compounds is confirmed by the methods of ¹H and ¹³C NMR spectroscopy and for five compounds by the X-ray diffraction study. Most compounds have an ionic character in crystals and in solutions, even for the complex with a sterically shielded silver atom (IPr)₂AgNO₃ and monocarbene complexes. Synthesized complexes show high antibacterial (MIC up to 1.9 μg/mL on <em>M. luteum</em>) and antifungal activity (MIC up to 0.9 μg/mL on <em>A. niger</em> and 1.9 μg/mL on <em>C. tenuis</em>).</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100298"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-target candidate compounds from a transformer chemical language model contain characteristic structural features","authors":"Sanjana Srinivasan ,&nbsp;Alec Lamens ,&nbsp;Jürgen Bajorath","doi":"10.1016/j.ejmcr.2025.100291","DOIUrl":"10.1016/j.ejmcr.2025.100291","url":null,"abstract":"<div><div>Chemical language models (CLMs) are increasingly used for generative design of candidate compounds for medicinal chemistry. However, their predictions are difficult to rationalize. Currently, detailed computational explanations of CLM-based compound generation are unavailable. Therefore, we have attempted to better understand from a medicinal chemistry perspective how CLMs learn and arrive at compound predictions. Therefore, we have subjected dual-target candidate compounds for polypharmacology generated with transformer CLMs to a series of analysis steps exploring structural features that are learned and compared them to known compounds with dual-target activity. Using machine learning combined with distinct chemical structure-oriented approaches from explainable artificial intelligence, we show that CLMs learn substructures characteristic of known dual-target compounds as a basis for generating new candidates with various chemical modifications.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100291"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of mitochondrial potassium BKCa channel by naringenin derivatives: application of a new cellular model","authors":"Aleksandra Sęk ,&nbsp;Silvia Cammarone ,&nbsp;Rafał P. Kampa ,&nbsp;Karolina Pytlak ,&nbsp;Barbara Kalenik ,&nbsp;Joanna Lewandowska ,&nbsp;Francesca Ghirga ,&nbsp;Isabella Romeo ,&nbsp;Omar Atrooz ,&nbsp;Piotr Bednarczyk ,&nbsp;Adam Szewczyk ,&nbsp;Bruno Botta ,&nbsp;Deborah Quaglio ,&nbsp;Bogusz Kulawiak","doi":"10.1016/j.ejmcr.2025.100304","DOIUrl":"10.1016/j.ejmcr.2025.100304","url":null,"abstract":"<div><div>Mitochondrial potassium (mitoK) channels play a crucial role in mitochondrial and cellular physiology. One of the best described mitoK channels is the mitochondrial large-conductance calcium-activated potassium (mitoBK_Ca) channel. It has been shown that activation of the mitoBK_Ca channel protects the heart and brain tissue against ischemia/reperfusion injury. This channel may be formed in mitochondria by the VEDEC isoform of the α subunit encoded by the KCNMA1 gene. In addition to regulation by canonical channel blockers and potassium channel openers, this channel is regulated by flavonoids, including naringenin. Our work aimed to establish and use a new cellular model to investigate the role of new naringenin derivatives in regulating the activity of the mitoBK_Ca channel. We developed HEK293 cells stably expressing the VEDEC isoform of the BK_Ca (HEK293-BK_DEC). Using the patch-clamp technique on isolated mitoplasts from the newly established cell line, we detected the activity of a potassium channel exhibiting all the characteristics of the mitoBK_Ca channel, such as a conductance of 289 pS, voltage-dependent changes in opening probability, channel activation by calcium ions, and inhibition by paxilline. Additionally, introducing the VEDEC isoform into HEK293 cells led to an increase in the mitochondrial oxygen consumption rate and a change in the expression of certain genes encoding mitochondrial proteins involved in oxidative phosphorylation. Subsequently, we investigated the influence of new naringenin derivatives on the activity of the mitoBK_Ca channel. We observed that depending on the type of modification of this flavonoid, the channel could be activated or inhibited by the tested naringenin derivatives. In summary, we have developed a new experimental model enabling the study of mitoK channel activity with a defined molecular structure exemplified by the mitoBK_Ca channel. This model can be used to test new modulators of the mitochondrial potassium channels, which could be employed for further physiological studies in the future.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100304"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New promising transthyretin stabilizers for cardiac amyloidosis treatment","authors":"Lidia Ciccone ,&nbsp;Caterina Camodeca ,&nbsp;Carole Fruchart-Gaillard ,&nbsp;Robert Thaï ,&nbsp;Nicolò Tonali ,&nbsp;Giuseppina Basta ,&nbsp;Serena Del Turco ,&nbsp;Lara Russo ,&nbsp;Magali Noiray ,&nbsp;Serena Sirigu ,&nbsp;William Shepard ,&nbsp;Lucia Barlettani ,&nbsp;Francesco Mazzocchi ,&nbsp;Elisabetta Orlandini ,&nbsp;Susanna Nencetti","doi":"10.1016/j.ejmcr.2025.100308","DOIUrl":"10.1016/j.ejmcr.2025.100308","url":null,"abstract":"<div><div>Transthyretin (TTR) is a plasma protein responsible for transport of thyroxine and retinol, the latter through binding with the retinol-binding protein. In contrast with its physiological role, TTR possesses an intrinsic amyloidogenic potential due to the high content of β-strands. Under pathological conditions, TTR undergoes a misfolding process forming protein aggregates and fibrils that cause organ damage and dysfunction, leading to the onset of TTR amyloidosis diseases (ATTRs). One therapeutic approach against ATTRs progression involves administering small molecules able to bind the inner channel of the protein enhancing tetramer stability. Here, we report the synthesis and characterization of 2-(((benzyloxy)imino)methyl)benzoic acids (<strong>1a-l</strong>), 3-(((benzyloxy)imino)methyl)benzoic acids (<strong>2a-l</strong>) and 4-(((benzyloxy)imino)methyl)benzoic acids (<strong>3a-l</strong>) as new potential inhibitors of TTR fibril formation. Our study shows that compounds <strong>1a</strong> ((<em>E</em>)-2-((((2-(trifluoromethyl)benzyl)oxy)imino)methyl)benzoic acid)), <strong>1d</strong> ((<em>E</em>)-2-((((2-chlorobenzyl)oxy)imino)methyl)benzoic acid), <strong>2l</strong> ((<em>E</em>)-3-((((2-chloro-6-fluorobenzyl)oxy)imino)methyl)benzoic acid) and <strong>3g</strong> ((<em>E</em>)-4-((((2-methoxybenzyl)oxy)imino)methyl)benzoic acid) effectively inhibit the aggregation of wild-type TTR (wt-TTR) and mutants (V30M, V122I). Among these derivatives <strong>1a</strong> and <strong>1d</strong> have stronger ability to contrast the fibril formations. The binding affinity of <strong>1a</strong>, <strong>1d</strong>, <strong>2l</strong> with TTR (wt, V30M and V122I) was determined by fluorescence displacement assay and isothermal titration calorimetry. The binding modes of the selected ligands have been confirmed by X-ray crystallography. Moreover, these compounds show no toxicity in endothelial and cardiomyocyte cells, reinforcing their potential as TTR stabilizers.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100308"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TCS-isatin-INH triads as potent and selective anti-mycobacterial with high efficacy against Mycobacterium tuberculosis","authors":"Shekhar ,&nbsp;Francoise Roquet-Banères ,&nbsp;Laurent Kremer ,&nbsp;Vipan Kumar","doi":"10.1016/j.ejmcr.2025.100307","DOIUrl":"10.1016/j.ejmcr.2025.100307","url":null,"abstract":"<div><div>A series of novel Triclosan–Isatin–Isoniazid triads were synthesized and evaluated for antitubercular activity. These hybrids showed potent efficacy against <em>Mycobacterium tuberculosis</em> with low minimum inhibitory concentrations (MICs) ranging from 0.78 to 1.56 μg/mL, along with high selectivity indices, indicating strong activity with minimal cytotoxicity in human macrophages. Time-kill assays revealed bactericidal effects, with some hybrids achieving sustained bacterial growth suppression comparable to INH at equivalent MICs. At higher doses, a 3-log reduction in bacterial viability was achieved within three days, with one triad showing an additional 1-log reduction by day six. Mechanistic evaluation using INH-resistant <em>katG</em> mutant strains revealed reduction in activity, indicating KatG-dependent bioactivation. Cytotoxicity assays confirmed low toxicity (IC₅₀ &gt; 100 μg/mL), underscoring their potential as safe and effective anti-TB agents.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100307"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, and binding analysis of target-specific covalent inhibitors of SARS-CoV-2 papain-like protease","authors":"Martynas Bagdonas ,&nbsp;Laimonas Stančaitis ,&nbsp;Ernestas Urniežius ,&nbsp;Audrius Zakšauskas ,&nbsp;Aurelija Mickevičiūtė ,&nbsp;Rūta Kananavičiūtė ,&nbsp;Audronė Rukšėnaitė ,&nbsp;Vaida Juozapaitienė ,&nbsp;Jurgita Matulienė ,&nbsp;Visvaldas Kairys ,&nbsp;Franz-Josef Meyer-Almes ,&nbsp;Asta Zubrienė ,&nbsp;Daumantas Matulis","doi":"10.1016/j.ejmcr.2025.100306","DOIUrl":"10.1016/j.ejmcr.2025.100306","url":null,"abstract":"<div><div>The global emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 2019 resulted in widespread consequences for human health, with an ongoing situation six years later. Despite extensive efforts, the virus continues to circulate, resulting in a persistent rate of new diagnoses and fatalities. The potential for future outbreaks is heightened by the emergence of new mutations, underscoring the need for effective additional treatment options, such as antiviral drugs, to prevent the difficulties experienced during the COVID-19 pandemic. In this study, a structure-guided ligand design strategy was applied to optimize the SARS-CoV-2 papain-like protease (PL^pro) inhibitor GRL0617 and enhance its potency. A series of covalent inhibitors was synthesized, and their inhibition potential, target-specificity, binding mode, and selectivity against several human proteases were evaluated. Two compounds, <strong>LS 22</strong>–<strong>5</strong> and <strong>AZ 23</strong>–<strong>6</strong>, demonstrating the nanomolar inhibition potential of PL^pro, were identified as lead compounds for antiviral drug design.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100306"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing of compound libraries yields new inhibitors of NDM-1 metallo-β-lactamase with diverse zinc-binding moieties","authors":"Vid Kavaš ,&nbsp;Philip Hinchliffe ,&nbsp;Maša Zorman ,&nbsp;Alen Krajnc ,&nbsp;Matic Proj ,&nbsp;Majda Golob ,&nbsp;Martina Hrast Rambaher ,&nbsp;James Spencer ,&nbsp;Stanislav Gobec","doi":"10.1016/j.ejmcr.2025.100282","DOIUrl":"10.1016/j.ejmcr.2025.100282","url":null,"abstract":"<div><div>Antimicrobial resistance has emerged as a critical global public health threat, impacting human, animal and environmental health. An important mechanism of resistance is the production of β-lactamases, enzymes that hydrolyze the β-lactam ring, rendering β-lactam antibiotics ineffective. Metallo-β-lactamases (MBLs), which contain zinc ions in their active sites, are particularly challenging to counter as there are currently no inhibitors targeting these enzymes available on the market. Therefore, there is an urgent need for innovative drug discovery strategies to develop MBL-targeted therapies. New Delhi Metallo-β-Lactamase 1 (NDM-1) is the most widely disseminated MBL, with a global distribution in <em>Enterobacterales</em>. In this study, we used our library of fragment-sized chloroacetamides as a starting point to synthesize mercaptoacetamides as potential NDM-1 inhibitors. This resulted in a compound (<strong>14a</strong>) with an IC₅₀ of 20 μM, which crystallography shows binds to NDM-1 in two different poses. Using this structure as a starting point for <em>in silico</em> design, we developed a series of larger thiol-based compounds designed to occupy more space in the active site and to utilize other novel zinc-binding groups. Although some showed minimal inhibition (which makes them valuable as decoys for metalloenzyme studies) one compound exhibited an IC₅₀ of 14 μM, with crystallography indicating that an additional aromatic group, compared to <strong>14a</strong>, interacts with hydrophobic residues on an NDM-1 active site loop. These data identify promising scaffolds for the further development of potent MBL inhibitors and show the utility of repurposing chemical libraries to target clinically important enzymes.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100282"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144364922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New cytotoxic dolabellane and dolastane diterpenes from Brown seaweed Dictyota dichotoma","authors":"Kolukula Ashwini ,&nbsp;Bandi Siva ,&nbsp;Penta Poornima ,&nbsp;Solipeta Divya Reddy ,&nbsp;Hashnu Dutta ,&nbsp;Vedula Girija Sastry ,&nbsp;Katragadda Suresh Babu","doi":"10.1016/j.ejmcr.2025.100286","DOIUrl":"10.1016/j.ejmcr.2025.100286","url":null,"abstract":"<div><div>Five new dolabellane (<strong>1</strong>–<strong>5</strong>), three dolastane (<strong>6</strong>–<strong>8</strong>) type diterpenes together with five previously identified congeners (<strong>9</strong>–<strong>13</strong>), were isolated from the organic extracts of the brown seaweed <em>Dictyota dichotoma,</em> collected in the Mandapam coast, Tamil Nadu. The structures and relative stereochemistry of the new isolates <strong>1</strong>–<strong>8</strong> were determined on the basis of extensive spectroscopic (NMR and Mass spec) data, whereas the structures of <strong>10</strong> and <strong>12</strong> were verified by X-ray diffraction analysis. A plausible biogenetic relationship between undescribed compounds <strong>1</strong>–<strong>8</strong> were also proposed. The <em>in vitro</em> anti-cancer activity of the isolates was examined against a panel of cancer cell lines, including DU145 (prostate), B16F10 (melanoma), HeLa (cervical), and MDA-MB231 (breast) using MTT assay. The screening results showed that majority of the isolated compounds exhibited moderate to potent activities against tested cell lines. Among the tested, compounds <strong>4</strong> and <strong>7</strong> manifested potent activities with an IC₅₀ value of 3.53 ± 0.05 and 2.18 ± 0.06 μM respectively, against B16F10 and DU145 cells. Further, detailed fluorescence assays, scratch assay and flow cytometry analysis revealed that the compounds <strong>4</strong> and <strong>7</strong> diminished proliferation and arrested cell cycle in the G0 phase and G0/G1 phase, which induced cell death by apoptosis. Overall, this study provided that compounds <strong>4</strong> and <strong>7</strong> could serve as lead molecules for the development of potent anti-cancer agents.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100286"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144686406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacognosy and natural product chemistry of the marine sponge Hyrtios erectus","authors":"Christian Bailly","doi":"10.1016/j.ejmcr.2025.100303","DOIUrl":"10.1016/j.ejmcr.2025.100303","url":null,"abstract":"<div><div>Marine-derived bioactive natural products are an essential resource for drug discovery. In particular, marine sponges and associated symbionts can be exploited to discover innovative compounds and new drug candidates. The sponge <em>Hyrtios erectus</em> which is largely distributed in Asian tropical areas, has been extensively investigated as a source of bioactive natural products. A detailed analysis of the natural products isolated from this sponge and their pharmacological properties has been performed. The study led to the identification of over 160 natural products, including over 50 alkaloids, 100 terpenoids and a few other compounds like phenolic alkenes (erectuseneols), chromanones (hyrtiosones) and cyclic peptides (spongitatin-1). The survey introduces multiple series of products, such as the hyrtiosins, hyrtiosulawesine, hyrtiazepine, hyrtioerectines, hyrtioreticulins, hyrtimomines, hyrtinadines, and hainanerectamines among the alkaloids. A large range of sesterterpenes and sesquiterpenes have been isolated, in particular scalarane-type sesterterpenoids such as erectascalaranes A-B, hyrtioscalaranes A-B and hyrtiosins A-F, in addition to a panoply of scalarin and scalaradial derivatives. All these compounds are presented together with their pharmacological properties. Synthetic procedures leading to some of these natural products and analogues are described, notably for hyrtiozulawesine, hyrtinadine A, hytiosine B, and salmahyrtisol A. At the pharmacological level, the most interesting products and associated molecular targets are discussed, such as the targeting of the orphan nuclear receptor Nur77 with 12-<em>epi</em>-scalaradial derivatives. An updated view of the chemical and pharmacological diversity associated with <em>Hyrtios erectus</em> is provided with the goal to promote further researches with this sponge erected as an emblematic figure of the marine natural product chemistry.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"15 ","pages":"Article 100303"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145320176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}