European Journal of Medicinal Chemistry Reports最新文献

{"title":"Design, synthesis, α-glucosidase inhibition and hypoglycemic activity of 3-aceto(benzo)hydrazide-1,2,4-triazines as potential anti-diabetic agents","authors":"Mehdi Valipour ,&nbsp;Zahra Zakeri Khatir ,&nbsp;Kaveh Kiadaliry ,&nbsp;Somayeh Mojtabavi ,&nbsp;Mohammad Ali Faramarzi ,&nbsp;Mohammad Shokati Sayyad ,&nbsp;Mohammad Seyedabadi ,&nbsp;Majid Ghasemian ,&nbsp;Seyedeh Mahdieh Hashemi ,&nbsp;Hamid Irannejad","doi":"10.1016/j.ejmcr.2024.100207","DOIUrl":"10.1016/j.ejmcr.2024.100207","url":null,"abstract":"<div><p>Type 2 diabetes is a common condition that causes the level of glucose in the blood to become too high and α-glucosidase inhibitors are therapeutic agents in managing type 2 diabetes. I<em>n</em> the present study, we report a new series of 3-aceto(benzo)hydrazide-1,2,4-triazine analogs as potential therapeutic agents against type 2 diabetes. In the <em>in vitro</em> evaluations, most compounds showed much stronger α-glucosidase inhibitory activity than the standard drug acarbose. Especially, compound <strong>2A</strong>, (N'-(5,6-diphenyl-1,2,4-triazin-3-yl)-4-methoxybenzohydrazide) as the most active compound showed IC₅₀ = 12.0 μM which is 60 folds more potent than acarbose. In addition, the MTT test using the three cell lines HCT-116, MDA-MB-231, and A549 showed that the target compounds have low cytotoxic effects with IC₅₀ values in the range of 60–280 μM, therefore they can be considered as safe compounds. Molecular docking studies predicted that the strong inhibitory activity of <strong>2A</strong> is related to the interactions generated by the three residues Asp282, Trp481, and Asp616 with the triazine core and hydrazide motif in the active site of the enzyme. The significant inhibitory effect of <strong>2A</strong> against α-glucosidase was also confirmed <em>in vivo</em>, where the compound showed equivalent activity to the standard drug acarbose on reducing blood glucose in the tested mice. In conclusion, this study introduces compound <strong>2A</strong> as a new lead compound with favorable cytotoxicity, strong α-glucosidase inhibitory activity and <em>in vivo</em> hypoglycemic effect, for future investigation in the treatment of diabetes mellitus.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100207"},"PeriodicalIF":0.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000797/pdfft?md5=9de0dfb2df03e62a5b57ea51f13b23da&pid=1-s2.0-S2772417424000797-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142039198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis and antitumor activity of 3,4,5-Trisubstituted Isoxazoles","authors":"Kanghui Duan ,&nbsp;Fuxing Tan ,&nbsp;Hongming Xie ,&nbsp;Haiwang Liu ,&nbsp;Yingjun Zhang ,&nbsp;Huanfeng Jiang ,&nbsp;Wanqing Wu","doi":"10.1016/j.ejmcr.2024.100203","DOIUrl":"10.1016/j.ejmcr.2024.100203","url":null,"abstract":"<div><p>In this study, 56 isoxazole derivatives were synthesized and their antitumor activity against 9 cancer cells, such as BXPC-3, MiaPaCa-2, PANC-1, MCF-7, HCT-116, HepG2, NCI-H460, A549 and B16 was detected. The results of pharmacological experiments indicated that most compounds exhibit good cytotoxicity against nine cancer cells. Among them, compound <strong>14</strong>–<strong>3</strong> has an IC₅₀ of 2.4 μM for colon cancer cells HCT-116, which shows the best effect and is better than the broad-spectrum drug 5-Fluorouracil (5-Fu) for the treatment of colon cancer. In addition, <strong>14</strong>–<strong>3</strong> induces apoptosis and leads to cell cycle arrest in the G2/M phase. Cytotoxicity tests on human normal hepatocytes LO2 also demonstrates that <strong>14</strong>–<strong>3</strong> is less toxic than 5-Fu with no obvious toxicity. These results suggest that <strong>14</strong>–<strong>3</strong> is a potential candidate for the development of anti-tumor drugs.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100203"},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277241742400075X/pdfft?md5=d9d5bb3d63fdd470bae8fe1359c4c765&pid=1-s2.0-S277241742400075X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microneedles in cosmetology: A SWOT analysis","authors":"Shweta Singh ,&nbsp;Rimpa Karmakar ,&nbsp;Devkant Pundir,&nbsp;Akash Singh,&nbsp;Sakshi Soni,&nbsp;Monika Vishwakarma,&nbsp;Arpana Purohit,&nbsp;Sushil K. Kashaw,&nbsp;Vandana Soni","doi":"10.1016/j.ejmcr.2024.100197","DOIUrl":"10.1016/j.ejmcr.2024.100197","url":null,"abstract":"<div><h3>Background</h3><p>Cosmetic microneedling has emerged as a popular minimally invasive technique. This systematic review employs the SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis framework to comprehensively evaluate the current landscape of cosmetic microneedles.</p></div><div><h3>Method</h3><p>The review incorporates a rigorous examination of peer-reviewed articles, the number of publications from the year 2008–2023, clinical trials, market products and devices available, and patents related to cosmetic microneedles. The selection criteria include relevance to SWOT analysis, publication quality, and recency. A systematic and transparent methodology is employed to ensure the inclusion of the most pertinent and reliable evidence available.</p></div><div><h3>Conclusion</h3><p>Microneedle systems in cosmetic applications reveal a dynamic landscape marked by strengths such as precise drug delivery and self-administration potential. However, these cutting-edge mechanisms face challenges, including concerns about skin damage and regulatory complexities. Opportunities lie in the targeted delivery capabilities across diverse cosmetic treatments, from hair growth to scar reduction and anti-wrinkle therapy. Incorporating artificial intelligence (AI) and machine learning into microneedling procedures has the potential to transform numerous aspects of cosmetic treatment. The insights gained from this analysis are relevant for practitioners, researchers, and industry professionals, guiding future research directions, technological advancements, and strategic decision-making in the cosmetic microneedling domain.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100197"},"PeriodicalIF":0.0,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000694/pdfft?md5=65c2e7c36a528447fd5fa7e2e1945413&pid=1-s2.0-S2772417424000694-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142099080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting capsaicin and nonivamide: Their analogs exert strong inhibitory activity against cholinesterases","authors":"Niels V. Heise,&nbsp;Jeremy Quast,&nbsp;René Csuk","doi":"10.1016/j.ejmcr.2024.100200","DOIUrl":"10.1016/j.ejmcr.2024.100200","url":null,"abstract":"<div><p>The scientific community has long been interested in capsaicin, and the extensive hunt for AChE and BChE enzyme inhibitors is still ongoing. In this investigation analogs of capsaicin, such as the pharmaceutical nonivamide, which is preferred in clinical settings for the topical treatment of pain, were explored in the search for appropriate inhibitors. Thus, to test their inhibitory effect on AChE and BChE, we synthesized a short series of derivatives derived from vanillylamide. Consequently, it was discovered that compounds <strong>12</strong>, <strong>34</strong>, and <strong>35</strong>, which have K_i values in the sub-micromolar concentration range, are especially effective inhibitors. Compound <strong>12</strong> demonstrated dual mixed-type (competitive/uncompetitive) inhibitory activity for both enzymes; compound <strong>34</strong> showed selective mixed-type inhibitory activity for AChE, and compound <strong>35</strong> was found to have selective uncompetitive activity for AChE.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100200"},"PeriodicalIF":0.0,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000724/pdfft?md5=c7581ccd38237ac9d42b9d9e9c8b2eb3&pid=1-s2.0-S2772417424000724-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142039581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemistry and pharmacological activities of essential oils, flavonoids, and ascorbic acid in Smyrnium olusatrum L.: A comprehensive review","authors":"Zineb Sekkout,&nbsp;Amal EL Hamsas EL Youbi,&nbsp;Omaima Boudaia,&nbsp;Driss Radallah,&nbsp;Najat EL Amrani","doi":"10.1016/j.ejmcr.2024.100201","DOIUrl":"10.1016/j.ejmcr.2024.100201","url":null,"abstract":"<div><p>Conventional pharmaceutical interventions often entail considerable financial burdens and are frequently associated with a plethora of adverse effects. Consequently, an escalating number of individuals are turning to herbal remedies to ameliorate the symptoms of various ailments. Nonetheless, a significant proportion of medicinal plants remain underexplored. <em>Smyrnium olusatrum</em> L., a biennial herbaceous plant belonging to the Apiaceae family, colloquially known as Alexanders or Wild celery, has been traditionally employed in the treatment of colds and hemorrhages. Pharmacological investigations have highlighted the abundant presence of flavonoids and ascorbic acid in this plant. However, predominant research focus has been directed towards its essential oils. Intriguingly, a myriad of compounds derived from <em>Smyrnium olusatrum</em> L. exhibit noteworthy antioxidant, anticancer, anti-inflammatory, antimicrobial, and antiparasitic activities. The primary objective of this review is to elucidate structural variabilities in compounds across distinct plant parts and geographical origins of <em>Smyrnium olusatrum</em> L. Additionally, this review seeks to systematically compile data pertaining to the diverse biological effects observed both <em>in vitro</em> and <em>in vivo</em>, thereby elucidating the underlying mechanisms governing these effects.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100201"},"PeriodicalIF":0.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000736/pdfft?md5=1c700189e4018e2e70b9f1310a0f895a&pid=1-s2.0-S2772417424000736-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141993378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metronidazole delivery strategies: Optimizing cancer therapy through novel approaches for enhanced delivery, cytotoxicity, and side effect reduction","authors":"Hamed Ahmadi ,&nbsp;Mohammadali Heydari ,&nbsp;Majid Abdouss ,&nbsp;Zahra Jamalpoor ,&nbsp;Sonia Fathi-karkan ,&nbsp;Abbas Rahdar ,&nbsp;Sadanand Pandey","doi":"10.1016/j.ejmcr.2024.100202","DOIUrl":"10.1016/j.ejmcr.2024.100202","url":null,"abstract":"<div><p>Metronidazole (MTZ) is a vital antimicrobial agent widely used in the treatment of various infections. However, its limited bioavailability and associated side effects necessitate the development of efficient drug delivery systems to enhance therapeutic efficacy and minimize adverse reactions. The field of nanotechnology and nanomaterials presents promising solutions for delivering MTZ, leveraging their unique properties to overcome these challenges. This comprehensive review explores a variety of nanomaterial-based approaches for MTZ delivery, emphasizing the benefits such as improved drug stability, targeted release, and enhanced bioavailability. Various nanocarrier systems, including polymeric nanoparticles, lipid-based nanocarriers, and inorganic nanoparticles, are evaluated for their potential in MTZ delivery applications. The review underscores strategies aimed at reducing MTZ's side effects through controlled release and targeted delivery, with nanocarriers facilitating sustained drug release to minimize fluctuations in drug concentrations and potentially mitigate adverse reactions linked to MTZ administration. Furthermore, innovative combination therapies involving MTZ and other drugs are investigated for their ability to enhance therapeutic outcomes and combat drug resistance. Co-delivery systems show promise in synergistically targeting infections while reducing overall dosage and associated side effects. By summarizing the latest advancements in MTZ delivery, this review provides valuable insights into the potential of nanotechnology-based strategies for optimizing MTZ therapy. These approaches have the potential to transform drug delivery, offering safer and more effective treatments for infectious diseases, and improving patient outcomes by reducing adverse effects.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100202"},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000748/pdfft?md5=586d935768f5faa545b5a83aa0ad54ca&pid=1-s2.0-S2772417424000748-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calendula in modern medicine: Advancements in wound healing and drug delivery applications","authors":"Ovinuchi Ejiohuo ,&nbsp;Samson Folami ,&nbsp;Abdulkadir Yusif Maigoro","doi":"10.1016/j.ejmcr.2024.100199","DOIUrl":"10.1016/j.ejmcr.2024.100199","url":null,"abstract":"<div><p>Calendula, commonly known as marigold, is a plant of the Asteraceae family with a rich history of medicinal use. This plant possesses a variety of bioactive compounds, including steroids, terpenoids, triterpenoids, phenolic acids, flavonoids, carotenoids, and essential oils. These compounds confer significant anti-inflammatory, antioxidant, antimicrobial, and anticancer properties to Calendula, making it a promising candidate for treating various skin conditions, particularly skin wounds. Calendula extracts hold potential applications in the pharmaceutical, food, and cosmetic industries. Notably, these extracts can be utilized in drug delivery systems as natural biomaterials, offering benefits for various health conditions. This review aims to provide an updated synthesis of the medical and pharmacological uses of Calendula, with a focus on its role in wound healing and drug delivery systems. It addresses the limitations of using Calendula's active compounds, offering insights for future research and application.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100199"},"PeriodicalIF":0.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000712/pdfft?md5=a31f8a18d26425e9b6ab9d405553f80d&pid=1-s2.0-S2772417424000712-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141978466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"(Iso)quinoline amides derived from corosolic acid exhibit high cytotoxicity, and the potential for overcoming drug resistance in human cancer cells","authors":"Niels V. Heise ,&nbsp;René Csuk ,&nbsp;Thomas Mueller","doi":"10.1016/j.ejmcr.2024.100198","DOIUrl":"10.1016/j.ejmcr.2024.100198","url":null,"abstract":"<div><p>Previous research on acetylated pentacyclic triterpenes had demonstrated the excellent cytotoxic action and, in certain situations, very surprising selectivity of (iso)-quinolinyl amides, in particular. Specifically, compounds derived from asiatic acid or maslinic acid had demonstrated promising outcomes. To investigate the influence of the different arrangement of the two methyl groups in ring E (compared to maslinic acid) and the absolute configuration of the hydroxyl groups in ring A (compared to asiatic acid), corosolic acid was chosen as starting material. Corsolic acid was acetylated and transformed into the corresponding quinolinyl amides <strong>3</strong>–<strong>7</strong> and isoquinolinyl amides <strong>8</strong>–<strong>13</strong> using various amino–(iso)–quinolines for a systematic investigation. Their analysis using SRB assays revealed that several of the synthesized amides exhibited significant cytotoxicity against a range of human cancer cell lines. Notably, compound <strong>6,</strong> a 7-amino-quinoline derivative, emerged as the most potent, demonstrating not only high cytotoxicity but also good selectivity for tumor cells and a remarkable ability to overcome drug resistance. The highest selectivity index was obtained for compound <strong>4</strong> – a 5-amino-quinoline derivative - and HT29 colorectal carcinoma cells with SI &gt; 74.6, and compound <strong>13</strong> – a 8-isoquinoline derivative – with a SI = 58.5 while under the same conditions standard doxorubicin showed only SI = 2.9.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100198"},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000700/pdfft?md5=94ef2e2eb2b5b7fa87cbfada69077cc9&pid=1-s2.0-S2772417424000700-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141952538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flavonoid derivatives treat dextran sodium sulfate-induced experimental colitis in mice by inhibiting MAPK/NF-κB pathway activation","authors":"Cen Xiang ,&nbsp;Quanyuan Qiu ,&nbsp;Chunmei Zhang ,&nbsp;Yandong Leng ,&nbsp;Mengzhen Yuan ,&nbsp;Yao Rong ,&nbsp;Futao Liu ,&nbsp;Lianbo Zhao ,&nbsp;Zhen Liu ,&nbsp;Yunsong Chang ,&nbsp;Yu-Ou Teng","doi":"10.1016/j.ejmcr.2024.100196","DOIUrl":"10.1016/j.ejmcr.2024.100196","url":null,"abstract":"<div><p>Flavonoids are widely found in plants and diets and are considered to possess a variety of biological activities. Therefore, in this study, 8 novel compounds derivating from the precursor compound <strong>1a</strong>, were designed and synthesized, and their activities against ulcerative colitis(UC) were evaluated to provide the most active molecule <strong>2d</strong>. Both a cellular inflammation model by LPS(Lipopolysaccharide)-induced RAW 264.7 cells and the UC model in 2 % Dextran Sulfate Sodium(DSS) intragastrically injected mice were established and employed to detect and validate the effects and mechanisms of compound <strong>2d</strong> on ulcerative colitis. Cell experiments showed that compound <strong>2d</strong> possesses the best anti-UC activity among all derivatives (<strong>2a-d, 3a-d</strong>). Compound <strong>2d</strong> could significantly inhibit the release of inflammatory cytokines such as TNF-α, IL-6, IL-1β and IL-8 in RAW264.7 cells induced by LPS at 10 μM. RAW264.7 cells. In vivo experiments further demonstrated that compound <strong>2d</strong> could effectively treat UC in mice induced by DSS. The results indicated that compound <strong>2d</strong> restored MPO oxidative stress, reduced the secretion of inflammatory factors, and regulated the expression of NF-κB and MAPK pathway-related proteins, which was consistent with the results at the cellular level. The results of the relevant intestinal flora showed that compound <strong>2d</strong> could normalize the intestinal flora of mice with ulcerative colitis. In summary, compound <strong>2d</strong> may inhibit inflammation and oxidative stress by regulating NF-κB and MAPK pathways, and restore the diversity of intestinal microbiota to treat ulcerative colitis. It provides a new approach for the clinical application of flavonoids.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100196"},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000682/pdfft?md5=c0028a6e282827043849e0e8af5832c1&pid=1-s2.0-S2772417424000682-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141979138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of O-GlcNAcylation in Alzheimer's disease: Insights and perspectives","authors":"Anjali Sharma ,&nbsp;Arshdeep Singh ,&nbsp;Rabin Debnath ,&nbsp;Ghanshyam Das Gupta ,&nbsp;Kalicharan Sharma","doi":"10.1016/j.ejmcr.2024.100195","DOIUrl":"10.1016/j.ejmcr.2024.100195","url":null,"abstract":"<div><p>O-GlcNAcylation is a critical post-translational modification involving the addition of N-acetylglucosamine to serine/threonine residues on proteins, significantly influencing their function and stability. In Alzheimer's disease (AD), the modification of the tau protein by O-GlcNAcylation is crucial to its pathophysiology. Tau, which is essential for neuronal microtubule stability, has 80 potential Ser/Thr residues for O-GlcNAcylation. This modification is regulated by O-GlcNAc transferase (OGT), which adds O-GlcNAc groups, and O-β-N-acetyl-<span>d</span>-glucosaminidase (O-GlcNAcase or OGA), which removes them. O-GlcNAcylation competes with phosphorylation—a key factor in tau pathology—by directly occupying phosphorylation sites or glycosylating adjacent residues, thus potentially inhibiting tau hyperphosphorylation and aggregation. The novelty of this approach lies in targeting OGA with inhibitors to increase overall O-GlcNAcylation levels of tau and other proteins, potentially reducing hyperphosphorylation and aggregation associated with AD progression. By inhibiting OGA, these agents can elevate O-GlcNAcylation, offering a protective mechanism against tauopathies and other neurodegenerative changes in AD. This strategy highlights the innovative potential of OGA inhibitors as therapeutic agents, suggesting they could modify disease progression and improve clinical outcomes in AD patients. The development and application of OGA inhibitors thus represent a groundbreaking direction for future therapeutic strategies in combating Alzheimer's disease.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100195"},"PeriodicalIF":0.0,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000670/pdfft?md5=696ff6389dbbbb9ad216f5850ddde431&pid=1-s2.0-S2772417424000670-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141951980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}