Current medicinal chemistry最新文献

{"title":"Recent Advancement of Fecal Microbiota Transplantation in the Treatment of Ulcerative Colitis- A Review.","authors":"Yiting Lin, Peiru Wang, Xi Hu, Qinjia Wang, Quan Shi, Yanna Zhou, Ruisheng Liu, Xianbin Cai","doi":"10.2174/0109298673404225250730100935","DOIUrl":"https://doi.org/10.2174/0109298673404225250730100935","url":null,"abstract":"<p><p>Fecal Microbiota Transplantation (FMT) involves the transfer of gut microbiota from healthy donors to recipients, aiming to reestablish microbial equilibrium within the gastrointestinal tract. The human gut harbors a complex and diverse microbial ecosystem, comprising bacteria, viruses, and fungi, that is essential for maintaining intestinal homeostasis. Emerging evidence indicates a strong association between gut microbial dysbiosis and the pathogenesis of Ulcerative Colitis (UC). FMT has been shown to modulate microbial composition, alter immune signaling pathways, enhance intestinal barrier function, and influence the production of proinflammatory mediators, thereby affecting disease progression. This review critically examines the efficacy, safety, modulatory factors, combination therapies, and predictive strategies associated with FMT in the context of UC. The findings suggest that FMT represents a highly promising therapeutic modality for UC. Overall, this review aims to provide a comprehensive and impartial synthesis of current knowledge regarding FMT, offering deeper insights into its therapeutic potential and clinical applicability in UC management.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hybrids/Conjugates/Chimera Drugs-Antimicrobial Hybrids: Antibiotics, Antifungals, Antituberculars, Antimalarials.","authors":"Abraham Nudelman","doi":"10.2174/0109298673362583250705102313","DOIUrl":"https://doi.org/10.2174/0109298673362583250705102313","url":null,"abstract":"<p><p>Antimicrobial hybrids are compounds that can inhibit, stop the growth of, or kill microorganisms, including bacteria, fungi, and parasites. Antibiotics, a subset of an-timicrobial agents, specifically target bacteria and include well-established classes such as β-lactams, macrolides, quinolones, and oxazolidinones. Other antimicrobial hybrids are designed for treating a wide range of diseases, including fungal infections, leish-maniasis, parasitic diseases (such as trypanosomiasis and malaria), leprosy, and tuber-culosis. Some hybrids are designed to treat a variety of diseases. This review highlights studies primarily published between 2000 and 2023, with a few from 2024, underscor-ing the dynamic and rapidly evolving nature of antimicrobial hybrid research.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Participation of MDM2 in Pro-Apoptotic and Androgen Receptor-Degrading Potency of Selected Steroid and Terpenoid Derivatives.","authors":"Alexander Y Misharin, Alexander V Veselovsky, Vladimir A Zolottsev","doi":"10.2174/0109298673373971250625075309","DOIUrl":"https://doi.org/10.2174/0109298673373971250625075309","url":null,"abstract":"<p><p>This review aims to highlight anti-proliferative, pro-apoptotic, and androgen receptor-degrading activity of selected steroid and terpenoid derivatives in cancer cells, primarily in prostate cancer cells. Steroid and terpenoid derivatives (steroid hybrids, comprising androstane or pregnane skeleton associated with nitrogen containing hetero-cycle, some natural sterols, bile acids, and related semi-synthetic derivatives; oleanane and ursane type pentacyclic triterpenoids; lanostane and dammarane type tetracyclic triterpenoids), were reported earlier to cause the death of cancer cells via apoptosis; some compounds exhibited significant anticancer potency in vivo and may be consid-ered as promising anticancer agents. The presented data indicate that direct interaction of steroid and terpenoid derivatives with the key oncogenic protein MDM2 makes a significant contribution to anti-proliferative, pro-apoptotic, and androgen receptor-degrading activity of these compounds. It triggers apoptosis, which leads to cell death. Structural optimization of steroid and terpenoid derivatives can significantly increase their affinity to MDM2 and improve their anti-proliferative, pro-apoptotic, and andro-gen receptor-degrading activity.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Relationships Between Modifiable Risk Factors and Gastroesophageal Reflux Disease: A Two-Sample Mendelian Randomization Study.","authors":"Zhongqiu Zhou, Gang Shen, Wenying Zhou, Jiao Gong, Bo Hu","doi":"10.2174/0109298673372983250710031732","DOIUrl":"https://doi.org/10.2174/0109298673372983250710031732","url":null,"abstract":"<p><strong>Introduction: </strong>Gastroesophageal reflux disease (GERD) is a prevalent digestive disorder, yet the causal roles of modifiable risk factors remain unclear. This study aims to investigate the causal relationships between 28 modifiable risk factors (including obesity traits, mental health disorders, sleep traits, metabolic comorbidities, and serum parameters) and GERD using two-sample Mendelian randomization (MR). Gastroesophageal reflux disease (GERD). Our findings aim to inform targeted prevention and treatment strategies for GERD.</p><p><strong>Methods: </strong>This study obtained data from extensive genome-wide association studies (GWAS). Pooled data associated with gastroesophageal reflux associations were obtained from the 23andMe Research team's research, which included a total of 129,080 cases of gastroesophageal reflux and 473,524 controls of European ancestry. We conducted a univariable Mendelian randomization (MR) analysis to ascertain whether genetic evidence of exposure demonstrated a statistically significant association with the risk of GERD. Subsequently, a multivariable MR analysis was carried out to estimate the independent effects of the exposures on GERD.</p><p><strong>Results: </strong>Univariable MR analysis utilizing extensive GWAS data suggested that genetic factors such as BMI, Waist circumference, Arm fat mass (left and right), Leg fat mass (left and right), Attention Deficit and Hyperactivity Disorder (ADHD), Major Depressive Disorder (MDD), Schizophrenia, Negative emotions (including nervousness, anxiety, tension, or depression), Insomnia, Sleep apnea syndrome, Sleep duration, and Snoring, as well as Total cholesterol levels and Apolipoprotein B levels, are associated with the development of GERD. Multivariate Mendelian randomization of BMI and Negative mood as correction factors showed that Waist circumference, Arm fat mass (left and right), Leg fat mass (left and right), ADHD, Insomnia, Sleep apnea syndrome, and Snoring were associated with an increased risk of GERD (p< 0.05). Conversely, longer sleep duration was associated with a reduced risk of GERD (p< 0.05).</p><p><strong>Discussion: </strong>This MR study reveals novel causal mechanisms in GERD pathogenesis: (1) Peripheral adiposity (arm/leg fat mass) exerts independent effects beyond central obesity, indicating site-specific fat distribution significance; (2) ADHD emerges as a distinct psychiatric risk factor independent of mood disorders; (3) Sleep apnea operates through BMI-independent pathways. Collectively, these findings redefine GERD pathophysiology, highlighting fat depot specificity and brain-gut interactions as critical mechanistic drivers.</p><p><strong>Conclusions: </strong>Overall, our findings suggest that multiple risk factors are associated with the risk of GERD. These results provide a theoretical basis for controlling body weight and plasticity, improving sleep habits, and preventing and timely seeking medical attention to reduc","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, Antiproliferative Activity, ADME Profiling, and Docking Studies of Novel 1, 2, 3-Triazole Derivatives of 2-Amino and 2-Mercaptobenzoxazole.","authors":"Robert Ostrički, Anja Rakas, Vesna Rastija, Leentje Persoons, Dirk Daelemans, Tatjana Gazivoda Kraljević","doi":"10.2174/0109298673393777250714045359","DOIUrl":"https://doi.org/10.2174/0109298673393777250714045359","url":null,"abstract":"<p><strong>Introduction: </strong>Benzoxazole is a privileged scaffold with diverse biological activities, and its hybridization with a 1,2,3-triazole ring can improve affinity and efficacy. This study aimed to synthesize novel 1,2,3-triazole derivatives of 2-aminobenzoxazole and 2-mercaptobenzoxazole, and to evaluate their antiproliferative activity, predicted pharmacokinetic properties, and molecular interactions with kinase targets.</p><p><strong>Methods: </strong>1,2,3-triazole derivatives of 2-aminobenzoxazole 3-15 and 2-mercaptobenzoxazole 18-32 were synthesized via cyclization, propargylation, and copper-catalyzed click reaction. Antiproliferative activity was evaluated against human cancer cell lines: LN-229, Capan-1, HCT-116, NCI-H460, DND-41, HL-60, K-562, and Z-138. The ADME properties of 1,2,3-triazole-benzoxazole hybrids were evaluated using the SwissADME tool. The most active compounds were assessed for Human Gastrointestinal Absorption (HGA) and Blood-Brain Barrier (BBB) permeability using the Egan model. Molecular docking was performed on serine/threonine kinase TAO2 and tyrosine kinase c-Src.</p><p><strong>Results: </strong>A series of novel 1,2,3-triazole derivatives of 2-amino 3-15 and 2-mercaptobenzoxazole 18-32 were synthesized via click chemistry. Coumarin-containing compounds 3 and 29 showed the most pronounced antiproliferative activity across all tested cell lines. Both demonstrated high predicted HGA and low likelihood of crossing the BBB. Compound 3 exhibited the highest binding affinity for TAO2, while compound 29 showed strong interaction with c-Src.</p><p><strong>Discussion: </strong>The results highlight the favorable influence of coumarin substitution on antiproliferative activity, with computational ADME and docking data supporting the observed in vitro efficacy.</p><p><strong>Conclusion: </strong>This study outlines a viable method for the synthesis of novel 1,2,3-triazole derivatives of 2-aminobenzoxazole and 2-mercaptobenzoxazole. Compounds 3 and 29 demonstrate promising antiproliferative activity and pharmacokinetic potential, supporting their further development as anticancer candidates.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Anti-Inflammatory Effects of Chloramphenicol via TLR4 Inhibition in Postoperative Hemorrhoid Treatment: A Clinico-Computational Cohort Study.","authors":"S Shityakov, N S Lubinets, E Skorb, E G Skurikhin, V Kravtsov","doi":"10.2174/0109298673378981250710055128","DOIUrl":"https://doi.org/10.2174/0109298673378981250710055128","url":null,"abstract":"<p><strong>Introduction: </strong>Postoperative hemorrhoidectomy wounds are prone to inflammation and microbial infection due to their anatomical location, necessitating effective therapeutic strategies. Chloramphenicol (CHL) is a broad-spectrum antibiotic with potential anti-inflammatory properties via Toll-like receptor 4 (TLR4) inhibition. This clinico- computational cohort study investigates CHL's dual therapeutic mechanism in postoperative hemorrhoid management, combining clinical outcomes with molecular modeling to elucidate its anti-inflammatory and antimicrobial effects.</p><p><strong>Methods: </strong>A prospective, controlled cohort study was conducted with 155 patients (55 CHL, 39 reference treatment [PR], 61 control) undergoing hemorrhoidectomy. CHL ointment (≤120 mg/day) was applied topically until granulation tissue appeared. Clinical outcomes, including edema resolution, granulation tissue formation, and pain scores, were assessed using ImageJ for wound area analysis and the visual analog scale (VAS) for pain. Molecular docking and dynamics simulations were performed using AutoDock and AMBER 22 to evaluate CHL's binding affinity to TLR4 compared to the reference inhibitor TAK-242. Statistical analyses included ANOVA, Mann-Whitney U tests, and post hoc power calculations.</p><p><strong>Results: </strong>CHL significantly accelerated wound healing, with 53.2% of patients achieving complete edema resolution by day 3 (vs. 43.6% by day 4) and faster granulation tissue formation (3.58 ± 0.60 days vs. 7.08 ± 1.20 days in controls, p<0.0001). Pain scores were significantly reduced in the CHL group. Molecularly, CHL exhibited superior TLR4 binding (ΔGtot = -25.97 kcal/mol vs. -20.69 kcal/mol for TAK-242), with stable complex formation and persistent interactions at Ile-135 (buried surface area: 350 Å2). Healing times were 13.5-19.8 days faster in the CHL group (mean 41 days vs. 54.5-60.8 days in controls).</p><p><strong>Conclusion: </strong>CHL demonstrates dual therapeutic potential in postoperative hemorrhoid management by inhibiting TLR4-mediated inflammation and microbial infection. Its superior binding affinity and clinical efficacy suggest it as a promising multifunctional agent. Further in vitro and long-term studies are needed to validate these findings and explore broader applications in surgical wound care.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New 4-Benzenesulfonamide Derivatives of Pyrazolo[1,5-<i>a</i>] [1, 3, 5]triazine as Purine Bioisosteres: Development, Synthesis, and Anticancer Perspective.","authors":"Ivan Semenyuta, Stepan Pilyo, Bohdan Demydchuk, Oleksandr Lyavinets, Volodymyr Brovarets","doi":"10.2174/0109298673385989250711112625","DOIUrl":"https://doi.org/10.2174/0109298673385989250711112625","url":null,"abstract":"<p><strong>Introduction: </strong>Seven new 4-[2-(dichloromethyl)pyrazolo[1,5-a][1,3,5]triazine derivatives were investigated for anticancer activity, possible molecular mechanisms of anticancer action, and ADMET properties.</p><p><strong>Methods: </strong>The 4-benzenesulfonamide derivatives of pyrazolo[1,5-a][1,3,5]triazine were synthesized using the condensation of N-(2,2-dichloro-1-cyanovinyl)-amides IV with 1H-pyrazol-5-amine. Compound antitumor activities were evaluated using the NCI-60 human cancer cell line. AutoDockTools and AutoDock Vina software were used for molecular modeling. Using the ADMETlab 3.0 and pkCSM web sources, the ADMET properties of compounds 4, 5, and 7 were calculated.</p><p><strong>Results: </strong>Seven new pyrazolo[1,5-a][1,3,5]triazine derivatives were synthesized. The compounds 4, 5, and 7 exhibit high activity >1 μM against leukemia, colon, and renal cancer. Compound 4 exhibited the most potent activity, with IC₅₀ values of 0.32 μM against leukemia, 0.49-0.89 μM against colon cancer, and 0.92 μM against renal cancer. Molecular modeling has demonstrated a potential antitumor mechanism involving CDK. The predicted ADMET profile of compounds 4, 5, and 7 is favorable.</p><p><strong>Discussion: </strong>The seven novel pyrazolo[1,5-a][1,3,5]triazines, as purine bioisosteres, were developed, synthesized, and investigated by in vitro and in silico methods.</p><p><strong>Conclusion: </strong>Seven novel pyrazolo[1,5-a][1,3,5]triazine derivatives exhibited anticancer activity against the NCI-60 cancer cell lines. The compounds 4, 5, and 7 demonstrated strong anticancer activity, with growth inhibition (GI) values exceeding 50% across all nine cancer types tested. The most active compound, 4, is against leukemia, colon cancer, renal cancer, and lung cancer. All compounds exhibit low toxicity, with LC50 values of 100 μM or greater. The molecular docking of compounds 4, 5, and 7 revealed the potential to inhibit cancer-associated cyclin-dependent kinases. The predicted ADMET profiles of their compounds are favorable, providing a basis for further improvement of their anticancer activity.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of Resveratrol Derivatives as Novel Therapeutic Modulators of 11β-Hydroxysteroid Dehydrogenase 1 Activity in Metabolic Dysregulation.","authors":"Yousef A Bin Jardan, Mohammed Bourhia, Muhammad Shahab, Guojun Zheng, Jaouad Bensalah, Musaab Dauelbait","doi":"10.2174/0109298673376734250707194939","DOIUrl":"https://doi.org/10.2174/0109298673376734250707194939","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysregulation, encompassing conditions such as type 2 diabetes mellitus, obesity, metabolic syndrome, and dyslipidemia, poses an increasing global health burden. The dysregulation of 11β-hydroxysteroid dehydrogenase 1 (11β- HSD1), a key enzyme in glucocorticoid metabolism, has been strongly implicated in the pathogenesis of these disorders by influencing glucose homeostasis, lipid metabolism, and insulin sensitivity. Consequently, targeting 11β-HSD1 offers a promising therapeutic strategy for mitigating metabolic dysregulation and its associated complications.</p><p><strong>Aim: </strong>The study aimed to identify resveratrol derivatives with high binding affinity and inhibitory potential against 11β-HSD1, using computational approaches to evaluate their pharmacokinetic and toxicity profiles.</p><p><strong>Methods: </strong>A library of resveratrol derivatives was screened using molecular docking to identify high-affinity compounds. The hit compounds were further evaluated for absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, followed by molecular dynamics simulations to assess their stability.</p><p><strong>Results: </strong>The resveratrol cis-dehydrodimer emerged as the most promising candidate, demonstrating high binding affinity, favorable ADMET properties, and stability over a 200 ns simulation period. These findings suggest its potential as a small-molecule inhibitor of 11β-HSD1.</p><p><strong>Conclusion: </strong>The resveratrol cis-dehydrodimer represents a viable candidate for further experimental validation as a therapeutic agent for metabolic disorders. Future studies should include synthetic validation and in vivo testing to confirm its efficacy.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging Gaps in Long COVID Therapy: A Mini Review.","authors":"Wassan Nori, Zina Abdullah Hussein, Roaa Mokram Hamed, Mufeed Taha, Alexandru Cosmin Pantazi","doi":"10.2174/0109298673389691250709181809","DOIUrl":"https://doi.org/10.2174/0109298673389691250709181809","url":null,"abstract":"<p><strong>Introduction: </strong>Long COVID-19 (LC) is a condition that follows SARS-CoV- -2, an acute infection defined by persistent fatigue, dyspnea, and impaired cognitive function. LC presents a complex array that imposes ongoing challenges on global health, patients' quality of life, and functional capacity. Many inconsistencies surround its pathophysiology, diagnosis, prevention, and treatment. This review aims to cover missed gaps in LC with a special focus on therapeutic strategies concerning non-pharmacological, pharmacological, experimental, and innovative approaches for better patient management and outcomes, as well as to evaluate their effectiveness and guide future research.</p><p><strong>Methods: </strong>An online search was conducted using five digital repositories: PubMed, Scopus, Google Scholar, Web of Science, and the Cochrane Library. A combination of keywords associated with LC therapy was employed: \"long COVID, \"pharmacological options,\" \"non-pharmacological options,\" \"innovative strategies,\" \"experimental\", and\" quality of life (QOL).\" Relevant data were extracted and synthesized to categorize therapeutic approaches into subtypes. A critical analysis was conducted on their mechanism of action, indication, outcome, and limitations.</p><p><strong>Results: </strong>The pooled prevalence of LC was 42%, and the symptom duration ranged from 3 months to 2 years. The most important risk factors for LC were female sex, unvaccinated status, and cases with co-morbidities. Diagnosis of LC was challenging due to a lack of diagnostic standardization and reliable biomarkers.</p><p><strong>Discussion: </strong>Non-pharmacological strategies were employed first, showing diverse efficacies; however, the reported literature was hindered by small sampling. Pharmacological agents show promising results but need further validation. Experimental and innovative strategies need longer studies and validations.</p><p><strong>Conclusion: </strong>LC has imposed a significant burden on community health, necessitating the appropriate allocation of health resources and community support. Preventive and therapeutic interventions show promise, but the variability in patient response underscores the need for personalized approaches and more well-designed trials. Collaborative research and multi-disciplinary teams are needed to mitigate the long-term effects of LC and improve patient outcomes.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polysaccharides from Sepia Esculenta Ink Promote Apoptosis via Inhibition of Autophagy in Cisplatin-exposed Triple-Negative Breast Cancer Cells.","authors":"Wei Xiao, Zhen Lin, Ping Luo, Huazhong Liu","doi":"10.2174/0109298673379638250707061138","DOIUrl":"https://doi.org/10.2174/0109298673379638250707061138","url":null,"abstract":"<p><strong>Introduction: </strong>Sepia Ink Polysaccharide (SIP) is a well-characterized, marinederived glycosaminoglycan with demonstrated multifunctional properties; however, its pharmacological mechanisms remain unclear. This study aims to investigate the anti-tumor mechanism of SIP1 from Sepia esculenta ink in the treatment of triple-negative breast cancer (TNBC), with a focus on apoptosis and autophagy.</p><p><strong>Methods: </strong>MDA-MB-231 cells exposed to cisplatin (CP) and SIP1 were assessed for apoptosis and autophagy by evaluating cell morphology, apoptosis and autophagy rates, and the expression of key genes involved in these processes using double staining, flow cytometry, and Western blotting.</p><p><strong>Results: </strong>The data revealed that SIP1 induced apoptosis in TNBC cells, as demonstrated by an increased apoptosis rate, an elevated expression level of the Caspase-3 protein, a decreased expression of Bcl-2, and an elevated Bax/Bcl-2 ratio. Additionally, SIP1 did not impact autophagy. CP induced both apoptosis and autophagy of breast cancer cells. The combination of SIP1 and CP exhibited synergistic effects, enhancing apoptosis by 2.33-fold compared to SIP1 alone and 1.25-fold compared to CP alone, while simultaneously reducing autophagy levels (0.84-fold compared to CP alone), as verified by the Beclin 1 protein content.</p><p><strong>Discussion: </strong>This work discovered that SIP1, a sulfated glycosaminoglycan with a low content of sulfate ester groups derived from Sepia esculenta ink, induced apoptosis by inhibiting autophagy, providing a novel perspective for a deeper understanding of the anti-- tumor mechanism of SIP. Currently, the underlying molecular mechanisms by which SIP1 modulates the crosstalk between apoptosis and autophagy in TNBC cells remain unknown and require further investigation.</p><p><strong>Conclusion: </strong>This study demonstrates that SIP1 is effective in inducing apoptosis and promotes cisplatin-induced apoptosis by repressing cisplatin-induced autophagy in MDA-MB-231 cells.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}