Medicinal Chemistry最新文献

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Chitosan-Based Materials: A Comprehensive Review on Anticancer Drug Development. 壳聚糖基材料:抗癌药物研究综述
IF 1.9 4区 医学
Medicinal Chemistry Pub Date : 2025-07-22 DOI: 10.2174/0115734064388263250710083810
Faris J Tayeb, Mohammed Fareed Felemban, Amal Adnan Ashour, Alaa Shafie
{"title":"Chitosan-Based Materials: A Comprehensive Review on Anticancer Drug Development.","authors":"Faris J Tayeb, Mohammed Fareed Felemban, Amal Adnan Ashour, Alaa Shafie","doi":"10.2174/0115734064388263250710083810","DOIUrl":"https://doi.org/10.2174/0115734064388263250710083810","url":null,"abstract":"<p><p>Cancer remains one of the most formidable global health threats, responsible for millions of deaths annually due to the uncontrolled proliferation and spread of abnormal cells. The development of effective anticancer therapies is crucial, as anticancer drugs target key cellular mechanisms, including DNA replication, apoptosis, and essential signaling pathways. In this context, chitosan (CT) has emerged as a promising biomaterial for advancing cancer treatment. With its unique combination of biocompatibility, biodegradability, and versatility, CT is gaining significant attention as a platform for developing innovative drug delivery systems. Recent research has highlighted the potential of CT-based materials to enhance drug efficacy by enabling controlled release, improving bioavailability, and facilitating targeted tumor delivery. Further modifications to CT, such as carboxymethylation, sulfation, and graft copolymerization, have significantly expanded its application in cancer therapy, allowing for more efficient encapsulation of chemotherapeutic agents, reducing systemic toxicity, and combating multidrug resistance. This review focuses on the latest developments (2021-2024) in CT-based materials for anticancer drug delivery, exploring their design principles, therapeutic mechanisms, and clinical applications. Additionally, the review discusses the challenges faced in translating these promising systems to clinical practice and highlights future strategies for optimizing CT-based therapies to revolutionize cancer treatment.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690707","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}
引用次数: 0
Recent Advances in Molecular Docking Techniques: Transforming Perspectives in Distinct Drug Targeting and Drug Discovery Approaches. 分子对接技术的最新进展:不同药物靶向和药物发现方法的转变视角。
IF 1.9 4区 医学
Medicinal Chemistry Pub Date : 2025-07-21 DOI: 10.2174/0115734064384472250716144736
Rashid M Ansari, Radhika N Mundke, Yogeeta O Agrawal, Sameer N Goyal, Kartik T Nakhate, Sumit S Rathod
{"title":"Recent Advances in Molecular Docking Techniques: Transforming Perspectives in Distinct Drug Targeting and Drug Discovery Approaches.","authors":"Rashid M Ansari, Radhika N Mundke, Yogeeta O Agrawal, Sameer N Goyal, Kartik T Nakhate, Sumit S Rathod","doi":"10.2174/0115734064384472250716144736","DOIUrl":"https://doi.org/10.2174/0115734064384472250716144736","url":null,"abstract":"<p><strong>Introduction: </strong>Drug targeting and drug discovery methodologies are advancing rapidly due to recent developments in molecular docking techniques. Molecular docking forecasts the interactions between a small molecule, such as a potential medicine, and a target protein or receptor.</p><p><strong>Objectives: </strong>This comprehensive review focuses on significant advances in molecular docking algorithms such as Vina, Glide, and AutoDock, including their enhanced accuracy and efficiency in predicting drug-target interactions. It also examines how novel features, such as fragment-based docking, covalent docking, and virtual screening, have expanded the significance of docking in modern pharmaceutical research.</p><p><strong>Methods: </strong>The literature search was carried out by employing search engines such as PubMed and Google Scholar with keywords such as Molecular Docking, Lead-Optimization, Protein Flexibility, Fragment-Based Docking, Covalent Docking, and Virtual Screening.</p><p><strong>Results: </strong>This present state-of-the-art review highlights recent advances in various docking methodologies and their significant applications in drug discovery, while also discussing the scoring functions of some well-established studies. Furthermore, by predicting the interactions between putative medications and protein residues involved in the creation of covalent bonds, covalent docking provides new opportunities for targeting difficult drug-resistant mutations. The efficiency and precision of these simulations have been increased by improved sampling techniques and sophisticated algorithms, enabling the investigation of conformational changes and protein flexibility throughout the drug-binding process.</p><p><strong>Conclusion: </strong>These approaches may hasten the course of emerging new remedies, increase the precision of hit-finding, and make it easier to find cutting-edge treatments for a variety of diseases. Molecular docking alone is insufficient to ensure the safety and efficacy of a pharmacological agent for commercialization. While it predicts binding affinity and interaction, it does not account for pharmacokinetics, toxicity, off-target effects, or in vivo behavior. Therefore, experimental validation through MD simulation, ADMET, in vitro, in vivo, and clinical studies is essential.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690718","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}
引用次数: 0
Recent Advances in the Medicinal Chemistry of Cancer (Part II). 肿瘤药物化学的最新进展(第二部分)。
IF 1.9 4区 医学
Medicinal Chemistry Pub Date : 2025-07-18 DOI: 10.2174/0115734064428200250716113612
Işıl Yıldırım
{"title":"Recent Advances in the Medicinal Chemistry of Cancer (Part II).","authors":"Işıl Yıldırım","doi":"10.2174/0115734064428200250716113612","DOIUrl":"https://doi.org/10.2174/0115734064428200250716113612","url":null,"abstract":"","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682748","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}
引用次数: 0
A Search for New Amidrazone Derivatives Containing 4-Oxybut-2-enoic Acid Moiety as Antibacterial Agents. 含4-氧丁-2-烯酸的新型氨基腙类抗菌药物的研究。
IF 1.9 4区 医学
Medicinal Chemistry Pub Date : 2025-07-15 DOI: 10.2174/0115734064396576250706091217
Renata Paprocka, Monika Przybysz, Kamila Pośpieszyńska, Ashley Chepkoech, Dominika Jagleniec, Antoni Godlewski, Karolina Korczak, Małgorzata Wiese-Szadkowska, Jolanta Kutkowska
{"title":"A Search for New Amidrazone Derivatives Containing 4-Oxybut-2-enoic Acid Moiety as Antibacterial Agents.","authors":"Renata Paprocka, Monika Przybysz, Kamila Pośpieszyńska, Ashley Chepkoech, Dominika Jagleniec, Antoni Godlewski, Karolina Korczak, Małgorzata Wiese-Szadkowska, Jolanta Kutkowska","doi":"10.2174/0115734064396576250706091217","DOIUrl":"https://doi.org/10.2174/0115734064396576250706091217","url":null,"abstract":"<p><strong>Introduction: </strong>Bacterial diseases pose a significant challenge to modern medicine due to the rapid development of resistance by bacterial strains and the global migration of people, which facilitates the transmission of these diseases. Therefore, there is a need to develop new strategies to combat microorganisms and newer substances that could be used as antibiotics.</p><p><strong>Methods: </strong>Six new derivatives, <b>2a-2f</b>, containing a 4-oxybut-2-enoic acid moiety, were obtained by reacting amidrazones with maleic anhydride. The antimicrobial potency of compounds <b>2a-2f</b> was studied using the microdilution method against the following bacterial strains: <i>Escherichia coli, Yersinia enterocolitica, Pseudomonas aeruginosa, Staphylococcus aureus, Micrococcus luteus, Enterococcus faecalis, Gordonia rubripertincta, Mycobacterium smegmatis</i>, and the fungal strain <i>Candida albicans</i>. Their antiproliferative activity was tested in cultures of human peripheral blood mononuclear cells stimulated with phytohemagglutinin. The bioavailability parameters of new compounds were predicted using Molinspiration software.</p><p><strong>Results: </strong>Derivatives <b>2a-2c</b> showed the strongest antibacterial activity, especially against <i>Yersinia enterocolitica</i> and <i>Micrococcus luteus</i>. Compounds <b>2d-2f</b> inhibited the growth of <i>Gordonia rubripertincta</i>. Compounds <b>2a-2f</b> exhibited low antiproliferative activity towards human peripheral blood mononuclear cells. However, it is necessary to evaluate whether all compounds are well absorbed after oral administration.</p><p><strong>Discussion: </strong>The most promising antibacterial activity was demonstrated by derivatives possessing a 2-pyridyl substituent at the R1 position (<b>2a-2c</b>) or a phenyl ring at the R<sup>2</sup> position (2a, 2f).</p><p><strong>Conclusion: </strong>Compound <b>2a</b> demonstrated the highest antibacterial activity and selectivity in inhibiting the growth of <i>Y. enterocolitica</i>. Additionally, it exhibited low toxicity to human lymphocytes and demonstrated favorable bioavailability parameters. Therefore, its structure can be used as a starting point for designing new antimicrobials, such as targeted therapies for yersiniosis, beyond traditional antibiotics.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649868","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}
引用次数: 0
Identification of Potential Dual HDAC6 and HSP90 Inhibitors for the Treatment of Cancer using Molecular Docking, Molecular Dynamics and MM/PBSA Studies: A Comprehensive In Silico Study. 利用分子对接、分子动力学和MM/PBSA研究鉴定治疗癌症的潜在双HDAC6和HSP90抑制剂:一项全面的硅研究
IF 1.9 4区 医学
Medicinal Chemistry Pub Date : 2025-07-07 DOI: 10.2174/0115734064388900250625121927
Muhsin Samet Yücel, İsmail Akçok
{"title":"Identification of Potential Dual HDAC6 and HSP90 Inhibitors for the Treatment of Cancer using Molecular Docking, Molecular Dynamics and MM/PBSA Studies: A Comprehensive <i>In Silico</i> Study.","authors":"Muhsin Samet Yücel, İsmail Akçok","doi":"10.2174/0115734064388900250625121927","DOIUrl":"https://doi.org/10.2174/0115734064388900250625121927","url":null,"abstract":"<p><strong>Background: </strong>Histone deacetylase 6 (HDAC6) and heat shock protein 90 (Hsp90) are crucial therapeutic targets in cancer research with their interconnected roles in regulating protein homeostasis and cellular processes. The interaction of these proteins within the cytosolic complex plays a critical role in regulating cancer cell survival and progression. Notably, current studies highlight that the simultaneous inhibition of HDAC6 and Hsp90 can produce synergistic effects and offer a promising therapeutic potential for combating malignant cancers.</p><p><strong>Objective: </strong>The objective of this study was to explore potential compounds that can inhibit both HDAC6 and Hsp90 proteins.</p><p><strong>Methods: </strong>In this study, a number of in-silico computational techniques were employed. A total of 791 molecules, sharing at least 30% similarity with previously identified four HDAC inhibitors, were obtained from the ZINC15 database and subjected to docking on HDAC6 and Hsp90 proteins. The top eight ligands demonstrating the best binding scores against both targets, with panobinostat and ganetespib serving as reference compounds for HDAC6 and Hsp90, respectively, were selected for further analysis. Subsequently, ADME prediction and molecular dynamics simulations were conducted on the selected ligands.</p><p><strong>Results: </strong>A detailed molecular docking, molecular dynamics simulations and ADME studies have revealed that ZINC27653366 exhibited the highest inhibitory potential against both Hsp90 and HDAC6 target proteins, making it the most promising inhibitor.</p><p><strong>Conclusion: </strong>In conclusion, although additional in vitro and in vivo studies are required for the validation, in silico evaluation of ZINC27653366 may position it as a promising candidate for the treatment of different types of cancers.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584310","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}
引用次数: 0
Antioxidant and Cytotoxic Activity of the Aporphine Alkaloid (Boldine) Against DMH-induced Colorectal Carcinogenesis in Wistar Rats: An In silico, In vitro, and In vivo study. 阿波啡生物碱(Boldine)抗dmh诱导的Wistar大鼠结直肠癌的抗氧化和细胞毒活性:一项硅、体外和体内研究。
IF 1.9 4区 医学
Medicinal Chemistry Pub Date : 2025-07-03 DOI: 10.2174/0115734064358287250613065507
Monu Kumar Kashyap, Akash Ved, Pranay Wal, Akhand Pratap Singh
{"title":"Antioxidant and Cytotoxic Activity of the Aporphine Alkaloid (Boldine) Against DMH-induced Colorectal Carcinogenesis in Wistar Rats: An <i>In silico, In vitro</i>, and <i>In vivo</i> study.","authors":"Monu Kumar Kashyap, Akash Ved, Pranay Wal, Akhand Pratap Singh","doi":"10.2174/0115734064358287250613065507","DOIUrl":"https://doi.org/10.2174/0115734064358287250613065507","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The objective of this study is to investigate the role of the aporphine alkaloid boldine as a potential inhibitor of specific protein targets involved in colorectal cancer, using &lt;i&gt;in silico&lt;/i&gt; docking and molecular dynamics simulation studies, and to evaluate its therapeutic potential in modulating the pathological progression of colorectal cancer. In this study, we evaluated the antioxidant and cytotoxic effects of boldine using &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt; methods.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The 2-dimensional structure of boldine was retrieved from the PubChem database. Its interactions with colorectal cancer target proteins were analyzed using structures obtained from the RCSB Protein Data Bank (https://www.rcsb.org/), which provides the crystal structures of tubulin (PDB ID: 1Z2B), human NF- κB (1A3Q), human interleukin-2 (1M47), and EGFR-kinase. Molecular docking was then performed using Schrödinger software. Molecular docking and molecular dynamics (MD) simulations were conducted to evaluate Boldine's binding affinity and stability with colorectal cancer protein targets. On the Growmac platform, we performed the molecular simulation, and the simulation was only done with the highest docking score. Additionally, molecular dynamics was performed for 100 ns. Boldine was added to the colorectal cancer cell line (HCT116) at different doses, and the cytotoxic effects of the treatment were evaluated using cell viability assays. Furthermore, Boldine's capacity to scavenge reactive oxygen species (ROS) and modify the oxidative stress assay &lt;i&gt;in vitro&lt;/i&gt; was used to assess its antioxidant capability. Boldine's in vivo anticancer effectiveness was examined using DMH-induced colorectal cancer in Wistar Rats. After Boldine was administered (100mg/Kg), Tumour progression, histological alteration, and oxidative stress markers were evaluated. The study aimed to ascertain how boldine affects tumor growth in DMH-inducedDMH colorectal carcinogenesis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Molecular docking revealed favorable binding interactions between boldine and key targets implicated in colorectal cancer. The &lt;i&gt;in silico&lt;/i&gt; data supported the hypothesis that boldine modulates essential pathways associated with cancer development. Boldine exhibited a dose-dependent reduction in colorectal cancer cell viability, indicating potential cytotoxic effects. Furthermore, boldine demonstrated antioxidant properties by effectively scavenging reactive oxygen species (ROS) and modulating oxidative stress markers in vitro. In animal models, boldine administration resulted in a significant reduction in tumor growth. Histopathological examination revealed favorable changes in tumor morphology. Additionally, boldine demonstrated antioxidant effects in vivo by modulating oxidative stress markers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;According to this extensive study performed &lt;i&gt;in silico&lt;/i&gt;, &lt;i&gt;in vitro&lt;/i&gt;, and &lt;i&gt;in vivo&lt;/i&gt;, bol","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575787","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}
引用次数: 0
Syntheses and Identification of New Dithiophosphinic Acid Complexes and Their Potential as Photodynamic Agents in Cancer Therapy. 新型二硫代膦酸配合物的合成、鉴定及其在癌症治疗中的光动力作用。
IF 1.9 4区 医学
Medicinal Chemistry Pub Date : 2025-07-03 DOI: 10.2174/0115734064382461250618113452
Kübra A Coşkun, Elif Bulat, Hamza Yılmaz, Ertuğrul Gazi Sağlam, Lutfi Tutar, Fayyaz Ur Rehman, Yusuf Tutar
{"title":"Syntheses and Identification of New Dithiophosphinic Acid Complexes and Their Potential as Photodynamic Agents in Cancer Therapy.","authors":"Kübra A Coşkun, Elif Bulat, Hamza Yılmaz, Ertuğrul Gazi Sağlam, Lutfi Tutar, Fayyaz Ur Rehman, Yusuf Tutar","doi":"10.2174/0115734064382461250618113452","DOIUrl":"https://doi.org/10.2174/0115734064382461250618113452","url":null,"abstract":"<p><strong>Background: </strong>The photo-efficacy of oncological phototherapy for both internal and external tumors is encouraging. When light and photochemotherapeutic drugs are applied together, precise cancer targeting, minimal invasiveness, and innovative modes of action are made possible. Current developments in photoactive compounds and new light sources are promising for further advancement.</p><p><strong>Objective: </strong>When designing photosensitizers, metal complexes may be advantageous since the metal can enhance stability and photocytotoxicity while facilitating their localization and quantification. The absorption spectra of photosensitizers limit their excitation wavelengths, which impact light tissue penetration that differs in various organs. Since longer wavelength light penetrates deeper, PDT is typically carried out at wavelengths greater than 620 nm. Additionally, employing lower intensity (>4-8 J/cm<sup>2</sup>) energy can greatly lessen the pain and discomfort induced by red-light PDT.</p><p><strong>Methods: </strong>Low-level laser therapy exposure was used to assess the dithiophosphinic acid complexes' photodynamic treatment efficacy in MCF-7 cells. Following the administration of the complexes at concentrations within IC<sub>50</sub> values, red light (4 J, 780 nm) was applied to the cells. Afterward, MCF-7 cells were cultured for 24 hours to evaluate the photodynamic effects of the compounds on cancer cells. Cell viability was assessed using the XTT assay kit.</p><p><strong>Results: </strong>DTPA complexes have shown effectiveness as photodynamic agents in cancer therapy, with Ni(II) and Ni(II)-pyridine complexes demonstrating significant cytotoxicity against cancer cells.</p><p><strong>Conclusion: </strong>Light-activated cancer cell therapies are promising, and the synthesized complexes affect the cell cycle and apoptosis-regulating proteins. The compounds can be employed as anticancer agents and a fine starting template for photodynamic drug design.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575788","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}
引用次数: 0
Promising Flavone Derivatives as Anticancer Agents. 黄酮衍生物作为抗癌剂的前景。
IF 1.9 4区 医学
Medicinal Chemistry Pub Date : 2025-07-02 DOI: 10.2174/0115734064384513250624043626
Vishakha A Patil, Kalyani R Thombre, Krishna Radheshyam Gupta, Milind Janrao Umekar
{"title":"Promising Flavone Derivatives as Anticancer Agents.","authors":"Vishakha A Patil, Kalyani R Thombre, Krishna Radheshyam Gupta, Milind Janrao Umekar","doi":"10.2174/0115734064384513250624043626","DOIUrl":"https://doi.org/10.2174/0115734064384513250624043626","url":null,"abstract":"<p><p><p> Currently, the main focus of anticancer drug development and research is to develop anticancer treatment strategies that are both less harmful and more effective. Flavones, a subclass of flavonoids, have shown great promise in the advancement of anticancer drugs because of their strong bioactive properties. Fruits, vegetables, and medicinal plants are abundant sources of these naturally occurring compounds, which have a variety of biological activities such as anti-inflammatory, anti-cancer, and antioxidant properties. Flavones and their derivatives have attracted a lot of attention recently because of their potential to modify significant molecular pathways that are involved in the growth, apoptosis, angiogenesis, and metastasis of cancer cells. The objective of this review is to present a thorough analysis of the chemical makeup of flavone as an anticancer agent. By altering the flavone scaffold's structure, there are beneficial chances to improve its therapeutic qualities, such as its potency, selectivity, and pharmacokinetics. The structural alterations of flavone derivatives that improve their anticancer potency and selectivity are highlighted. Most noteworthy, flavones offer a promising framework for the creation of new anticancer medications, and further research into them may help create more potent and focused cancer treatments.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560516","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}
引用次数: 0
Exploring the Cholinesterase Inhibitory Potential of Azines Bearing a 4,4-bisdimethylaminobenzophenone Scaffold: An Experimental and Computational Approach. 探索含4,4-二二甲氨基苯甲酮支架的氮嘧啶的胆碱酯酶抑制潜能:实验和计算方法。
IF 1.9 4区 医学
Medicinal Chemistry Pub Date : 2025-06-24 DOI: 10.2174/0115734064375363250620173232
Ghulam Ahad, Aftab Alam, Ahmed A Elhenawy, Imtiaz Ahmad, Fayaz Ur Rahman, Munir Ur Rehman, Abid Ali, Abdullah F AlAsmari, Fawaz Alasmari, Momin Khan
{"title":"Exploring the Cholinesterase Inhibitory Potential of Azines Bearing a 4,4-bisdimethylaminobenzophenone Scaffold: An Experimental and Computational Approach.","authors":"Ghulam Ahad, Aftab Alam, Ahmed A Elhenawy, Imtiaz Ahmad, Fayaz Ur Rahman, Munir Ur Rehman, Abid Ali, Abdullah F AlAsmari, Fawaz Alasmari, Momin Khan","doi":"10.2174/0115734064375363250620173232","DOIUrl":"https://doi.org/10.2174/0115734064375363250620173232","url":null,"abstract":"<p><strong>Background: </strong>Acetyl and butyrylcholinesterase are significant enzymes involved in neurological diseases, and the development of more effective inhibitors is crucial for beneficial interference.</p><p><strong>Objective: </strong>To evaluate the cholinesterase inhibition effect of the synthetic bis-Schiff base compounds and discover the electronic properties as well as binding affinities through computational studies.</p><p><strong>Methods: </strong>The compounds were synthesized and screened against acetyl and butyrylcholinesterase inhibitory activities in-vitro, while DFT analysis and molecular docking studies were performed for the product compounds.</p><p><strong>Results: </strong>Seven compounds, including <b>2a, 2b, 2e, 2c, 2d, 2i</b>, and <b>2j</b>, exhibited excellent AChE activity, while nine compounds showed potent BChE inhibition compared to galantamine (IC50 = 156.4 ± 1.13 μM). Furthermore, the recent study on molecules 2a-e has provided valuable insights into their mechanism of action as inhibitors of the enzyme ChE, which is crucial for understanding how to regulate this enzyme's activity. Through the use of Time-Dependent Density Functional Theory (TD-DFT), the electronic characteristics of these molecules were meticulously examined, revealing that the Highest Occupied Molecular Orbitals (HOMO) are extensively delocalized across the molecular frameworks of the most active <b>2a-e</b> compounds. This suggests a significant degree of electron delocalization, which is often associated with chemical reactivity and stability. In comparison to standard galantamine, these compounds demonstrate a lower electrophilicity index, which is indicative of their increased biological efficacy and lower toxicity.</p><p><strong>Conclusion: </strong>These derivatives showed excellent AChE and BChE activities with favorable electronic properties and superior binding affinities, highlighting their potential as effective inhibitors as therapeutic agents.</p>","PeriodicalId":18382,"journal":{"name":"Medicinal Chemistry","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540808","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}
引用次数: 0
Optimized Strategies for the Synthesis and Structure-Activity Relationship of Imidazole as an Antiepileptic Drug. 抗癫痫药物咪唑的合成及构效关系优化。
IF 1.9 4区 医学
Medicinal Chemistry Pub Date : 2025-06-10 DOI: 10.2174/0115734064377779250529172030
Saloni Mangal, Salahuddin, Avijit Mazumder, Rajnish Kumar, Sapna Rani, Vimal Datt, Mohamed Jawed Ahsan, Mohammad Shahar Yar
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