European Journal of Medicinal Chemistry Reports最新文献_第2页

Corrigendum to “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” [Europ. J. Med. Chem. Rep. 12 (2024) 100193]

European Journal of Medicinal Chemistry Reports Pub Date : 2024-12-01 DOI: 10.1016/j.ejmcr.2024.100222

Vaia-Argyro Bakalakou , Barbara Mavroidi , Amalia D. Kalampaliki , Béatrice Josselin , Stéphane Bach , Alexios-Leandros Skaltsounis , Panagiotis Marakos , Nicole Pouli , Maria Pelecanou , Vassilios Myrianthopoulos , Sandrine Ruchaud , Ioannis K. Kostakis

引用次数: 0

Use of radiopharmaceuticals in the diagnosis of neurodegenerative diseases 使用放射性药物诊断神经退行性疾病

European Journal of Medicinal Chemistry Reports Pub Date : 2024-11-04 DOI: 10.1016/j.ejmcr.2024.100239

Anna Tempesta , Anna Tolomeo , Azzurra Stefanucci , Lorenza Marinaccio , Adriano Mollica

引用次数: 0

Novel small molecule-based acetylcholinesterase (AChE) inhibitors: From biological perspective to recent developments 基于小分子的新型乙酰胆碱酯酶（AChE）抑制剂：从生物学角度看最新进展

European Journal of Medicinal Chemistry Reports Pub Date : 2024-10-24 DOI: 10.1016/j.ejmcr.2024.100237

Anjali Sobha , Anand Ganapathy , Sangeetha Mohan , Nithya Madhusoodanan , Alansheeja D. Babysulochana , Kumaran Alaganandan , Sasidhar B. Somappa

{"title":"Novel small molecule-based acetylcholinesterase (AChE) inhibitors: From biological perspective to recent developments","authors":"Anjali Sobha , Anand Ganapathy , Sangeetha Mohan , Nithya Madhusoodanan , Alansheeja D. Babysulochana , Kumaran Alaganandan , Sasidhar B. Somappa","doi":"10.1016/j.ejmcr.2024.100237","DOIUrl":"10.1016/j.ejmcr.2024.100237","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a chronic neurodegenerative disorder that imposes a substantial socioeconomic burden globally. The increasing prevalence of AD, coupled with an incomplete understanding of its fundamental etiology and the absence of a definitive cure, has intensified research efforts in this area. Over the past decade, the cholinergic theory has garnered significant attention from researchers, particularly in the development of small molecule-based Acetylcholinesterase (AChE) inhibitors using molecular modelling and computer-aided drug discovery. In recent years, the focus has expanded to include multi-target-directed ligands (MTDLs), which address the multifaceted pathological mechanisms of AD. These ligands offer the potential to reduce amyloid-beta plaque accumulation, neurofibrillary tangle (NFT) formation, oxidative stress, and neuroinflammation, while also providing metal chelation properties and selective MAO-B inhibition. Despite the progress in small molecule-based AD therapeutics, issues related to toxicity and severe side effects have underscored the urgent need for novel drug development. This has spurred interest in the structural modification of existing drugs such as tacrine, donepezil, galantamine, and rivastigmine, as well as the synthesis of new molecules informed by structure-activity relationship (SAR) studies. In this review, we summarize and analyse recent advancements in small molecule-based AChE inhibitors, with a focus on various drug design strategies aimed at generating potent therapeutic candidates.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100237"},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571810","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}

引用次数: 0

Targeting Alzheimer's disease with novel dual-function 3,5-diaryl-4,5-dihydro-1H-pyrazole-1-carbothioamide derivatives 用新型双功能 3,5-二芳基-4,5-二氢-1H-吡唑-1-硫代甲酰胺衍生物治疗阿尔茨海默病

European Journal of Medicinal Chemistry Reports Pub Date : 2024-10-21 DOI: 10.1016/j.ejmcr.2024.100235

Aikaterini Katsogiannou , Danai Karta , Antonio Di Stefano , Sena Oner , Mehmet Enes Arslan , Adil Mardinoglu , Hasan Turkez , Stamatia Vassiliou , Ivana Cacciatore

{"title":"Targeting Alzheimer's disease with novel dual-function 3,5-diaryl-4,5-dihydro-1H-pyrazole-1-carbothioamide derivatives","authors":"Aikaterini Katsogiannou , Danai Karta , Antonio Di Stefano , Sena Oner , Mehmet Enes Arslan , Adil Mardinoglu , Hasan Turkez , Stamatia Vassiliou , Ivana Cacciatore","doi":"10.1016/j.ejmcr.2024.100235","DOIUrl":"10.1016/j.ejmcr.2024.100235","url":null,"abstract":"<div><div>In the field of medicinal chemistry, the versatility of the thiosemicarbazone scaffold makes it a promising platform for the development of next-generation pharmaceuticals. In this paper the thiosemicarbazone scaffold was explored to obtain novel series of derivatives: a) thiosemicarbazones <strong>15</strong>–<strong>31,</strong> and <strong>33</strong> containing a linear thiosemicarbazone scaffold, b) <strong>34</strong>–<strong>38</strong> and <strong>44</strong>–<strong>64</strong> containing pyrazoline ring, and c) <strong>39</strong>–<strong>43</strong> containing the dihydropyrimidine cycle. Among these, compounds <strong>21</strong>, <strong>23</strong>, <strong>26</strong>, <strong>33</strong>–<strong>35</strong>, <strong>37</strong>, <strong>38</strong>, <strong>44</strong>, <strong>57</strong>, <strong>61</strong>, and <strong>62</strong> demonstrated no significant cytotoxic effects on HDFa cells at concentrations up to 500 μg/mL. Importantly, compounds <strong>21</strong>, <strong>23</strong>, <strong>26</strong>, <strong>33</strong>, <strong>34</strong>, <strong>35</strong>, and <strong>37</strong> exhibited significant protective effects against neurotoxicity induced by beta-amyloid peptide (1-42) in differentiated SHSY-5Y cell cultures. Enzymatic assays targeting BACE1 and AChE revealed modest inhibitory activity in compounds <strong>21</strong>, <strong>23</strong>, and <strong>34</strong>, <strong>37</strong>, respectively. The identification of compounds with inhibitory effects and neuroprotective activity against beta-amyloid peptide (1-42) offers a platform for further optimization and refinement of these compounds to enhance their potency and selectivity.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100235"},"PeriodicalIF":0.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532747","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}

引用次数: 0

Hydroxyapatite–polymer nanocomposites for drug delivery applications: A mini review 用于给药应用的羟基磷灰石-聚合物纳米复合材料：微型综述

European Journal of Medicinal Chemistry Reports Pub Date : 2024-10-18 DOI: 10.1016/j.ejmcr.2024.100231

Farnaz Behmagham , Shahad Mohammed Dhiaa , Abbas Hameed Abdul Hussein , Usama Kadem Radi , Hiba Mushtaq , Ameer Hassan Idan , Esmail Vessally

{"title":"Hydroxyapatite–polymer nanocomposites for drug delivery applications: A mini review","authors":"Farnaz Behmagham , Shahad Mohammed Dhiaa , Abbas Hameed Abdul Hussein , Usama Kadem Radi , Hiba Mushtaq , Ameer Hassan Idan , Esmail Vessally","doi":"10.1016/j.ejmcr.2024.100231","DOIUrl":"10.1016/j.ejmcr.2024.100231","url":null,"abstract":"<div><div>Prescribing drugs in a traditional way causes drug resistance and side effects. New strategies are being developed to solve these problems and to deliver drugs safely and efficiently to damaged tissues. Drug delivery systems are one of the successful strategies for delivering drugs to the disease site in the body. Hydroxyapatite (HA) due to its similarity to the compositional of bone and tooth and biocompatibility has received more attention in biomedical applications. Nonetheless, its applications are restricted by lower mechanical potency, low colloidal stability, and uncontrolled drug release. The composition of HA with polymers removes its defects as a drug delivery system. Hence, this paper provides clear information on the latest Hydroxyapatite nanocomposites (HAP-PNs) improvements as drug delivery systems. So, it supplies a precise insight into the various synthesis methods of HAp-PNs and newly developed nanocarriers from HAp-PNs. Moreover, this review confers HAp-PNs nanocarrier's possible usage and restrictions in different fields of medicine.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100231"},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532744","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}

引用次数: 0

Fabrication, characterization and transdermal properties of double cross-linked gel beads with 4-n-butylresorcinol 含有 4-正丁基间苯二酚的双交联凝胶珠的制造、表征和透皮特性

European Journal of Medicinal Chemistry Reports Pub Date : 2024-10-18 DOI: 10.1016/j.ejmcr.2024.100232

Faxin Zhang , Mengsi Yin , Wanhui Shao , Xinyi Li , Hongmen Ren , Xianglong Wang , Mengju Xu , Qianchan Pang , Yan Cheng , Jianjun Xue , Haijie Hu , Mingyuan Li

{"title":"Fabrication, characterization and transdermal properties of double cross-linked gel beads with 4-n-butylresorcinol","authors":"Faxin Zhang , Mengsi Yin , Wanhui Shao , Xinyi Li , Hongmen Ren , Xianglong Wang , Mengju Xu , Qianchan Pang , Yan Cheng , Jianjun Xue , Haijie Hu , Mingyuan Li","doi":"10.1016/j.ejmcr.2024.100232","DOIUrl":"10.1016/j.ejmcr.2024.100232","url":null,"abstract":"<div><div>In this paper, sodium alginate (SA) -agarose double cross-linked gel beads were prepared to improve the solubility of 4-n-butylresorcinol and to reduce skin irritation. The wrappage material suitable for 4-nBR gel beads was SA-agarose double cross-linking material, and the internal inclusions were in the form of 4-n-butylresorcinol nanoemulsions (4-nBR NEs). Under the orthogonal fluorescence microscope, it was observed that the gel beads were spherical in shape, with smooth and rounded surfaces and permeable interiors. The encapsulation rate of the gel beads was 84.37 ± 3.56 %, and the average diameter was 1.93 ± 0.21 mm. Scanning electron microscopy showed that the gel beads were spherical in shape. The cumulative leakage rate of the gel beads on the 35 th day was 4.72 ± 0.06 %, suggesting that the gel beads encapsulated 4-butylresorcinol to good effect and with high stability. This proves that the gel beads wrapped with 4-nBR are highly effective and stable. <em>In vitro</em> skin permeability assessment verified the good skin permeability of nanoemulsions (NEs).</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100232"},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142579016","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}

引用次数: 0

Comprehensive review of DNA gyrase as enzymatic target for drug discovery and development 全面评述作为药物发现和开发酶靶的 DNA 回旋酶

European Journal of Medicinal Chemistry Reports Pub Date : 2024-10-16 DOI: 10.1016/j.ejmcr.2024.100233

K. Rajakumari , K. Aravind , M. Balamugundhan , Manjunathan Jagadeesan , Ambiga Somasundaram , Parthiban Brindha Devi , Pasiyappazham Ramasamy

{"title":"Comprehensive review of DNA gyrase as enzymatic target for drug discovery and development","authors":"K. Rajakumari , K. Aravind , M. Balamugundhan , Manjunathan Jagadeesan , Ambiga Somasundaram , Parthiban Brindha Devi , Pasiyappazham Ramasamy","doi":"10.1016/j.ejmcr.2024.100233","DOIUrl":"10.1016/j.ejmcr.2024.100233","url":null,"abstract":"<div><div>DNA gyrase is a member of the DNA topoisomerase protein family that catalyzes the conversion of different topological forms of DNA into one another. It is the sole enzyme that causes DNA to negatively supercoil. The enzyme is tetrameric with two GyrA (“A\") and two GyrB (“B\") subunits. DNA gyrase is an ideal target for medication because of its basic properties in bacterial cells and the lack of gyrase activity in eukaryotes. Antibacterial medications, including quinolones and derivatives based on coumarins that specifically target DNA gyrase, underscore the significance of the enzyme in the fight against bacterial infections. In addition to the typical antibiotic-binding sites, including novobiocin and fluoroquinolones, several other areas are being used in drug discovery. Simocyclinone, thiophene, gepotidacin, halogen atoms in the para position of the phenyl right-hand side (RHS) moiety, and coupled cell division B (CcdB) are examples of novel bacterial type II topoisomerase inhibitors (NBTIs). These binding sites are structurally and chemically active and inhibit the supercoiling activity of topoisomerase. This article provides an overview of DNA gyrase inhibition using synthetic and natural precursors aimed at medication development and discovery.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100233"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532743","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}

引用次数: 0

MolAnchor method for explaining compound predictions based on substructures 基于子结构解释化合物预测的 MolAnchor 方法

European Journal of Medicinal Chemistry Reports Pub Date : 2024-10-15 DOI: 10.1016/j.ejmcr.2024.100230

Alec Lamens , Jürgen Bajorath

{"title":"MolAnchor method for explaining compound predictions based on substructures","authors":"Alec Lamens , Jürgen Bajorath","doi":"10.1016/j.ejmcr.2024.100230","DOIUrl":"10.1016/j.ejmcr.2024.100230","url":null,"abstract":"<div><div>In medicinal chemistry, the impact of machine learning remains limited if predictions are not understood, which often precludes experimental follow-up. Therefore, chemically intuitive approaches that aid in model understanding and interpretation at the molecular level of detail are sought after. While feature attribution methods quantifying feature importance for model decisions are widely used in many areas, they must typically be combined with visualization techniques, if possible, to render the results accessible from a chemical viewpoint. On the other hand, there are approaches such as counterfactuals that yield closely related chemical structures with different prediction outcomes, providing direct access to structural features that critically influence model decisions. Herein, we introduce another approach designed to rationalize chemical predictions based on molecular structure. Therefore, we adapt principles underlying the anchor concept from explainable artificial intelligence (XAI) and alter them for molecular machine learning. The resulting method, termed MolAnchor, systematically identifies substructures in test compounds that determine property predictions, thus ensuring chemical interpretability. The MolAnchor methodology is made freely available to the medicinal chemistry community as a part of our study.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100230"},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442386","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}

引用次数: 0

Discovering bioactive phytoconstituents from Citrullus lanatus for antimicrobial and antioxidants therapeutic applications 从南瓜中发现具有生物活性的植物成分，用于抗菌和抗氧化治疗

European Journal of Medicinal Chemistry Reports Pub Date : 2024-10-15 DOI: 10.1016/j.ejmcr.2024.100229

Lakshmana Nakkalagadda Venkataravana, Jagadesh Uppin, Nikhitha Chinna Ramanjineyulu, Poojitha Gowribidanur Krishna, Jayaram Lakshmaiah Narayana

{"title":"Discovering bioactive phytoconstituents from Citrullus lanatus for antimicrobial and antioxidants therapeutic applications","authors":"Lakshmana Nakkalagadda Venkataravana, Jagadesh Uppin, Nikhitha Chinna Ramanjineyulu, Poojitha Gowribidanur Krishna, Jayaram Lakshmaiah Narayana","doi":"10.1016/j.ejmcr.2024.100229","DOIUrl":"10.1016/j.ejmcr.2024.100229","url":null,"abstract":"<div><div>In recent decades, significant interest in natural bioactive compounds has led many researchers to study plants as primary natural sources of bioactive compounds, mainly when considering a few biological properties, including antioxidant, antimicrobial, and anti-inflammatory activities, and as nutritional supplements with health benefits. We designed this study to explore the phytochemicals profiling of <em>Citrallus lanatus</em> and evaluate their <em>in vitro</em> bioactive properties<em>.</em> The methanol extraction of the watermelon's stem, rind, and leaf parts through Soxhlet extraction was analyzed using Gas Chromatography-Mass Spectrometry. The GC-MS profiling of <em>Citrullus lanatus</em> examines the presence of numerous bioactive phytoconstituents with potential biological activities such as antioxidant, anti-inflammatory, antimicrobial, anticancer, and other properties. We have evidenced that the stem, rind, and leaf extracts with significant antioxidant and antimicrobial activities against clinically relevant pathogens like <em>Salmonella typhi</em>, <em>Pseudomonas aeruginosa</em>, <em>Bacillus subtilis</em>, and <em>Staphylococcus aureus</em>. Overall, our study sheds light on exploring novel bioactive phytoconstituents from C<em>itrullus lanatus</em> and explore, harness these compounds' therapeutic potential for human health.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100229"},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532746","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}

引用次数: 0

Combination of heme oxygenase-1 inhibitors and temozolomide to improve the anticancer effect in glioblastoma 血红素加氧酶-1抑制剂与替莫唑胺联合使用提高胶质母细胞瘤的抗癌效果

European Journal of Medicinal Chemistry Reports Pub Date : 2024-10-09 DOI: 10.1016/j.ejmcr.2024.100227

Sebastiano Intagliata , Valeria Ciaffaglione , Valeria Consoli , Agata Grazia D'Amico , Luca Vanella , Valeria Pittalà , Federica Sodano , Marica Erminia Schiano , Valeria Sorrenti , Loredana Salerno

{"title":"Combination of heme oxygenase-1 inhibitors and temozolomide to improve the anticancer effect in glioblastoma","authors":"Sebastiano Intagliata , Valeria Ciaffaglione , Valeria Consoli , Agata Grazia D'Amico , Luca Vanella , Valeria Pittalà , Federica Sodano , Marica Erminia Schiano , Valeria Sorrenti , Loredana Salerno","doi":"10.1016/j.ejmcr.2024.100227","DOIUrl":"10.1016/j.ejmcr.2024.100227","url":null,"abstract":"<div><div>Heme oxygenase-1 (HO-1) is involved in the oncogenesis of glioblastoma (GBM). In this work, we investigated for the first time how the co-administration (combo) of the HO-1 inhibitors <strong>SI1/09</strong> or <strong>LS6/42</strong> with temozolomide (<strong>TMZ</strong>) or temozolomide acid (<strong>TMZ Ac</strong>) may influence the proliferation of U87MG GBM cell lines. Moreover, two novel TMZ/HO-1 inhibitors codrugs <strong>LS8/21</strong> and <strong>LS8/24</strong> were synthesised, characterised and tested. Results indicate that the combos <strong>TMZ</strong> or <strong>TMZ Ac</strong> with <strong>LS6/42</strong>, as well as the corresponding <strong>LS8/24</strong>, are more efficacious in reducing U87MG cell proliferation with respect to reference drugs, allowing a possible reduction of the <strong>TMZ</strong> dosage and related side effects in clinical practice. The chemical and enzymatic stability of the most potent codrug <strong>LS8/24</strong> was evaluated. The observed high potency performed by both combos and <strong>LS8/24</strong> in cells suggests that HO-1 inhibition may give additional contribution to the antiproliferative effect of <strong>TMZ</strong>.</div></div>","PeriodicalId":12015,"journal":{"name":"European Journal of Medicinal Chemistry Reports","volume":"12 ","pages":"Article 100227"},"PeriodicalIF":0.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418306","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}

引用次数: 0