European Journal of Medicinal Chemistry Reports最新文献

{"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}

{"title":"Ultrasensitive aptamer-based electrochemical nanobiosensor in diagnosis of prostate cancer using 2D:2D reduced graphene oxide/graphitic carbon nitride decorated with Au nanoparticles","authors":"Fatemeh Saeidi Tabar ,&nbsp;Mehrab pourmadadi ,&nbsp;Fatemeh Yazdian ,&nbsp;Hamid Rashedi ,&nbsp;Abbas Rahdar ,&nbsp;Sonia Fathi-karkan ,&nbsp;Luiz Fernando Romanholo Ferreira","doi":"10.1016/j.ejmcr.2024.100192","DOIUrl":"10.1016/j.ejmcr.2024.100192","url":null,"abstract":"<div><p>Prostate-specific antigen (PSA) remains the cornerstone for prostate cancer diagnosis. This study presents a highly sensitive aptamer-based electrochemical biosensor for PSA detection utilizing a novel two-dimensional (2D):2D reduced graphene oxide (rGO)/graphitic carbon nitride (g-C3N4) composite decorated with gold nanoparticles (Au NPs). The aptamer chains were immobilized on a glassy carbon electrode (GCE) modified with the rGO/g-C3N4/Au NPs composite. The successful synthesis of the nanomaterial and electrode modification were confirmed using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM). The electrochemical properties and selectivity of the modified GCE were characterized by cyclic voltammetry (CV), square wave voltammetry (SQW), and electrochemical impedance spectroscopy (EIS). The biosensor exhibited high selectivity towards PSA compared to potential interferents like carbohydrate antigen 15-3 (CA 15-3), bovine serum albumin (BSA), fetal bovine serum (FBS), and glucose (C6H12O6). Under optimized conditions, the biosensor achieved a rapid detection time of 30 min for PSA and a remarkable limit of detection (LOD) of 0.44 fM (femtomolar) using methylene blue (MB) as the redox mediator. The limit of quantification (LOQ) was also exceptionally low at 2.5 fM. The applicability of the developed biosensor was further validated by analyzing real serum samples, demonstrating its potential for clinical use.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100192"},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000645/pdfft?md5=98d9865be2b6633f6c12ac528f509c5c&pid=1-s2.0-S2772417424000645-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141962903","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":"Exploring the therapeutic potential of xanthones in diabetes management: Current insights and future directions","authors":"Riya Saikia ,&nbsp;Kalyani Pathak ,&nbsp;Pallab Pramanik ,&nbsp;Md Ariful Islam ,&nbsp;Shreyasi Karmakar ,&nbsp;Saptasikha Gogoi ,&nbsp;Manash Pratim Pathak ,&nbsp;Dibyajyoti Das ,&nbsp;Jon Jyoti Sahariah ,&nbsp;Mohammad Zaki Ahmad ,&nbsp;Aparoop Das","doi":"10.1016/j.ejmcr.2024.100189","DOIUrl":"10.1016/j.ejmcr.2024.100189","url":null,"abstract":"<div><p>The search for effective antidiabetic agents, both synthetic and natural, has intensified over the years. This review provides a comprehensive examination of xanthone compounds as potential antidiabetic agents, exploring their sources, chemical structures, and pharmacological properties. Xanthones have been shown to enhance insulin sensitivity, modulate glucose metabolism, and mitigate oxidative stress and inflammation through various mechanisms. Key molecular targets include AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptors (PPARs), α-amylase, and α-glucosidase.The review details in vitro studies demonstrating that xanthones like γ-mangostin and mangiferin inhibit α-amylase and α-glucosidase with IC₅₀ values of 3.2 μM and 5.6 μM, respectively, highlighting their potential to improve glucose metabolism. In vivo studies have shown that xanthones improve glucose homeostasis, lipid profiles, and overall glycemic control in diabetic models. For instance, mangiferin administration in streptozotocin-induced diabetic rats resulted in lower fasting blood glucose levels and improved HDL levels.Moreover, the safety profile and potential side effects associated with xanthone usage are discussed, providing a balanced view of their therapeutic potential. This review consolidates current knowledge on xanthones' antidiabetic properties and serves as a valuable resource for further research and development of these compounds as antidiabetic agents.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100189"},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277241742400061X/pdfft?md5=36666a3b385bc216adf9e85a35d32363&pid=1-s2.0-S277241742400061X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141838457","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":"The pyrazolo[4,3-c]pyrazole core as a novel and versatile scaffold for developing dual DYRK1A-CLK1 inhibitors targeting key processes of Alzheimer's disease pathology","authors":"Vaia-Argyro Bakalakou ,&nbsp;Barbara Mavroidi ,&nbsp;Amalia D. Kalampaliki ,&nbsp;Béatrice Josselin ,&nbsp;Stéphane Bach ,&nbsp;Alexios-Leandros Skaltsounis ,&nbsp;Panagiotis Marakos ,&nbsp;Nicole Pouli ,&nbsp;Maria Pelecanou ,&nbsp;Vassilios Myrianthopoulos ,&nbsp;Sandrine Ruchaud ,&nbsp;Ioannis K. Kostakis","doi":"10.1016/j.ejmcr.2024.100193","DOIUrl":"10.1016/j.ejmcr.2024.100193","url":null,"abstract":"<div><p>In the current study, we designed, synthesized, and characterized a series of substituted pyrazolo[4,3-<em>c</em>]pyrazoles. These novel compounds were evaluated <em>in vitro</em> for their inhibitory activity over a panel of protein kinases to determine their potential therapeutic applications against Alzheimer's disease. To gain deeper insight into the binding interactions between the most potent analogues and their respective kinase targets, advanced molecular simulations were performed. In parallel, the ability of pyrazolo[4,3-<em>c</em>]pyrazoles to inhibit Aβ40 aggregation was assessed using biophysical techniques such as circular dichroism and Thioflavin T assays. Our results highlight the specific heterocycle as a highly promising and synthetically versatile scaffold for developing inhibitors of both AD-relevant kinases and amyloid-β aggregation. Although more effort is needed to assess the possibility of developing multi-target inhibitors, pyrazolo[4,3-<em>c</em>]pyrazole analogues demonstrated significant activities against their individual targets, indicating substantial capacity of the heterocyclic scaffold for further optimization toward both directions. Overall, our findings emphasize the potential of properly substituted pyrazolo[4,3-<em>c</em>]pyrazoles as multifunctional agents targeting key processes in Alzheimer's disease pathology.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100193"},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000657/pdfft?md5=002c3aff6565dd193d3d19fb0567762c&pid=1-s2.0-S2772417424000657-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141846847","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":"Current status of 1,4-Naphthoquinones and their derivatives for wound healing","authors":"Pooja Kumari ,&nbsp;Vikramjeet Singh ,&nbsp;Vinay Kant ,&nbsp;Munish Ahuja","doi":"10.1016/j.ejmcr.2024.100194","DOIUrl":"10.1016/j.ejmcr.2024.100194","url":null,"abstract":"<div><p>Cutaneous wounds are a major healthcare concern affecting millions of people as they fail to heal properly and can result in life threatening conditions and high economic loss. Wound healing is a complex, multifaceted process involving four consequent stages: haemostasis, inflammation, proliferation, and tissue remodelling. These phases work in coordination to restore the integrity of damaged skin and underlying tissues. 1,4-Naphthoquinone compounds and their derivatives have emerged as promising candidates in wound management. Herein, natural compounds such as lawsone, juglone, shikonin, plumbagin along with their derivatives have been discussed for wound healing potential with special emphasis on structural activity relationships. This review provides a comprehensive discussion on the chemical reactivity, biological activities, and mechanisms of action of these naphthoquinone-based compounds, particularly their antibacterial properties, which play a crucial role in wound healing. The review highlights the importance of elucidating structure-activity relationships to overcome challenges associated with poor solubility, low antibacterial efficacy, and the presence of inevitable impurities in plant extracts. Additionally, the review emphasizes the significance of developing diverse naphthoquinone derivatives at the laboratory scale to expand the repertoire of potential wound healing agents.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100194"},"PeriodicalIF":0.0,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000669/pdfft?md5=1e1bdf02aeea0b615e24967ce00fbced&pid=1-s2.0-S2772417424000669-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141843219","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":"Antimicrobial effects of new tetrahydrofurans","authors":"Shanmugha Samy ,&nbsp;Manikandan Alagumuthu ,&nbsp;Milind Shrinivas Dangate","doi":"10.1016/j.ejmcr.2024.100191","DOIUrl":"10.1016/j.ejmcr.2024.100191","url":null,"abstract":"<div><p>The increasing challenge of antimicrobial resistance (AMR) necessitates abrupt attention to discovering a new class of antimicrobials. In this study, we made efforts to prepare some fluoro-phenyl tetrahydrofurans-based DNA gyrase inhibitors as anti-microbial agents. To obtain the title compounds difluoro phenyl tetrahydrofurans (<strong>1-12</strong>), we used fluorophenyl-tetrahydrofuran and methyl benzenesulfonate to react with isoxazole derivatives and heterocyclic compounds bearing secondary amines in the presence of dimethylformamide (DMF) and sodium hydride (NaH) or potassium carbonate (K₂CO₃). The compounds were obtained in moderate to excellent yields and were characterized with FTIR, HRMS, NMR, etc. Among all compounds (<strong>1-12</strong>), compounds <strong>1, 2, 11,</strong> and <strong>12</strong> were active against various Gram-positive and Gram-negative bacteria at a low concentration (MIC ranged between 1.25 and 9.75 μg/mL) and displayed low toxicity towards mammalian cells. We testified the <em>in vitro</em> DNA gyrase inhibitory potential for these compounds. A molecular docking study and an ADMET assessment study were carried out to understand the mode of interaction of ligand-DNA gyrase. In conclusion, we screened the compounds <strong>1, 2, 11,</strong> and <strong>12</strong> for further clinical and pre-clinical studies.</p></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100191"},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772417424000633/pdfft?md5=4f2a370c52787ef72459a9b5cfa2f867&pid=1-s2.0-S2772417424000633-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141851818","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}