RSC medicinal chemistry最新文献_第7页

Advances in detecting non-steroidal anti-inflammatory drugs (NSAIDs) using molecular receptors and nanostructured assemblies. 利用分子受体和纳米结构组件检测非甾体抗炎药（NSAIDs）的进展。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2024-11-13 DOI: 10.1039/d4md00661e

Avijit Kumar Das

{"title":"Advances in detecting non-steroidal anti-inflammatory drugs (NSAIDs) using molecular receptors and nanostructured assemblies.","authors":"Avijit Kumar Das","doi":"10.1039/d4md00661e","DOIUrl":"https://doi.org/10.1039/d4md00661e","url":null,"abstract":"The detection and quantification of non-steroidal anti-inflammatory drugs (NSAIDs) are crucial due to their widespread use and potential impact on human health and the environment. This review provides a comprehensive survey of the recent advancements in sensing technologies for NSAIDs, focusing on molecular receptors and nanostructured assemblies. Molecular receptors based on different fluorescent molecules such as anthracene, naphthalimide, squaraine, quinoline, BINOL, etc. offer high selectivity and sensitivity for NSAID detection. In parallel, nanostructured assemblies including CdSe/ZnS, Cd/S quantum dots (QDs), carbon dot-containing imprinted polymers, Ag and Au nanoparticles (NPs), hydrogel-embedded chemosensors, etc. were utilized for NSAID detection. This review highlights the different binding pathways with the change of various photophysical properties combining molecular recognition elements with nanomaterials to develop innovative sensors that achieve rapid, sensitive, and selective detection of NSAIDs. The review also discusses current challenges and future prospects in the field and based on reported designed receptors and nanostructured assemblies. To the best of our knowledge, no reviews have been reported on this topic so far. Thus, this review will fruitfully guide researchers to design various new molecular receptors and nanostructured materials to detect NSAIDs.","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SIGMAP: an explainable artificial intelligence tool for SIGMA-1 receptor affinity prediction. SIGMAP：用于预测SIGMA-1受体亲和力的可解释的人工智能工具。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2024-11-08 DOI: 10.1039/d4md00722k

Maria Cristina Lomuscio, Nicola Corriero, Vittoria Nanna, Antonio Piccinno, Michele Saviano, Rosa Lanzilotti, Carmen Abate, Domenico Alberga, Giuseppe Felice Mangiatordi

{"title":"SIGMAP: an explainable artificial intelligence tool for SIGMA-1 receptor affinity prediction.","authors":"Maria Cristina Lomuscio, Nicola Corriero, Vittoria Nanna, Antonio Piccinno, Michele Saviano, Rosa Lanzilotti, Carmen Abate, Domenico Alberga, Giuseppe Felice Mangiatordi","doi":"10.1039/d4md00722k","DOIUrl":"https://doi.org/10.1039/d4md00722k","url":null,"abstract":"Developing sigma-1 receptor (S1R) modulators is considered a valuable therapeutic strategy to counteract neurodegeneration, cancer progression, and viral infections, including COVID-19. In this context, in silico tools capable of accurately predicting S1R affinity are highly desirable. Herein, we present a panel of 25 classifiers trained on a curated dataset of high-quality bioactivity data of small molecules, experimentally tested as potential S1R modulators. All data were extracted from ChEMBL v33, and the models were built using five different fingerprints and machine-learning algorithms. Remarkably, most of the developed classifiers demonstrated good predictive performance. The best-performing model, which achieved an AUC of 0.90, was developed using the support vector machine algorithm with Morgan fingerprints. To provide additional, user-friendly information for medicinal chemists in the rational design of S1R modulators, two independent explainable artificial intelligence (XAI) approaches were employed, namely Shapley Additive exPlanations (SHAP) and Contrastive Explanation. The top-performing model is accessible through a user-friendly web platform, SIGMAP (https://www.ba.ic.cnr.it/softwareic/sigmap/), specifically developed for this purpose. With its intuitive interface, robust predictive power, and implemented XAI approaches, SIGMAP serves as a valuable tool for the rational design of new and more effective S1R modulators.","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Property-based optimisation of PROTACs. 基于属性的 PROTACs 优化。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2024-11-07 DOI: 10.1039/d4md00769g

James S Scott, Iacovos N Michaelides, Markus Schade

引用次数: 0

3-Thio-3,4,5-trisubstituted-1,2,4-triazoles: high affinity somatostatin receptor-4 agonist synthesis and structure-activity relationships. 3-硫代3,4,5-三取代-1,2,4-三唑：高亲和力生长抑素受体-4激动剂的合成及构效关系。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2024-11-07 DOI: 10.1039/d4md00597j

A Michael Crider, Audrey Hospital, Karin E Sandoval, William L Neumann, Stephen Kukielski, Lejla Garic, Kristen Ingold, Matthew Dunahoo, Khush N Srabony, Rafael Frare, Olivia Slater, Nathan Peel, Maria Kontoyianni, Ken A Witt

{"title":"3-Thio-3,4,5-trisubstituted-1,2,4-triazoles: high affinity somatostatin receptor-4 agonist synthesis and structure-activity relationships.","authors":"A Michael Crider, Audrey Hospital, Karin E Sandoval, William L Neumann, Stephen Kukielski, Lejla Garic, Kristen Ingold, Matthew Dunahoo, Khush N Srabony, Rafael Frare, Olivia Slater, Nathan Peel, Maria Kontoyianni, Ken A Witt","doi":"10.1039/d4md00597j","DOIUrl":"10.1039/d4md00597j","url":null,"abstract":"Somatostatin receptor-4 (SST4) is a therapeutic target for several conditions, including Alzheimer's disease, seizures, neuropsychiatric disorders, and pain. Our previous work on 1,2,4-triazole derivatives led to enhanced SST4 binding affinity, selectivity, and functional activity. Herein we report the discovery of 3-thio-1,2,4-triazole series as selective and high affinity SST4 agonists. Thirty-three compounds show <100 nM binding affinity, five of which had sub-nanomolar binding affinity and >300-fold selectivity over other SST subtypes. SST4 cAMP inhibition assay activity data aligned with the ligand binding affinity. Comparative docking results of the ligands under investigation with the cryo-EM and most recent model-built SST4 structures suggest similar trends in binding. Amino acids responsible for high and moderate affinity were identified, whereas poorer ligand conformations and limited interactions were observed with the low-affinity compounds. In summary, this study presents a novel series of high affinity SST4 agonists with corresponding in vitro activity, demonstrating viable therapeutic potential.","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antibacterial activity of the structurally novel C-2 amine-substituted analogues based on quinoxaline. 基于喹喔啉的结构新颖的 C-2 氨基取代类似物的抗菌活性。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2024-11-01 DOI: 10.1039/d4md00670d

Yuting Liu, Pengju Yang, Yunyun Zhou, Zhiwen Zhou

{"title":"Antibacterial activity of the structurally novel C-2 amine-substituted analogues based on quinoxaline.","authors":"Yuting Liu, Pengju Yang, Yunyun Zhou, Zhiwen Zhou","doi":"10.1039/d4md00670d","DOIUrl":"10.1039/d4md00670d","url":null,"abstract":"In the current study, we have designed and prepared a series of quinoxaline-based compounds, which were derived from o-phenylenediamine. Among them, compounds 5m-5p displayed good to moderate antibacterial activity with MICs of 4-16 μg mL-1 against S. aureus, 8-32 μg mL-1 against B. subtilis, 8-32 μg mL-1 against MRSA and 4-32 μg mL-1 against E. coli, respectively. Compound 5p, identified as a potent broad-spectrum antibacterial agent, demonstrated the strongest inhibitory effects against a range of bacterial strains and low cytotoxicity, thereby warranting further investigation. Compound 5p not only demonstrated the ability to disperse established bacterial biofilms but also induced a slower development of bacterial resistance compared to norfloxacin. Moreover, bactericidal time-kill kinetic studies revealed that at a high concentration of 3MIC, compound 5p was capable of directly killing MRSA cells. The subsequent postcontact effect (PCE) results showed that the growth rate of viable bacteria (MRSA) was greatly impacted and did not recover in less than 24 hours, even after antibacterial agent 5p was removed. The drug-like properties and ADME prediction exhibited that 5m-5p obeyed Lipinski's rule of five and therefore presumably maintained moderate to good bioavailability and human intestinal absorption rate when administered orally. Mechanistic investigations have elucidated that compound 5p exerted its antibacterial effect by compromising the structural integrity of bacterial cell membranes, resulting in the leakage of intracellular constituents and ultimately causing bacterial demise. Further studies in vivo have demonstrated that 5p exhibited potent antibacterial efficacy against MRSA in murine corneal infection models, particularly at elevated concentrations. The current dataset has also been meticulously analyzed to delineate the structure-activity relationships (SARs) of the synthesized compounds.","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adjuvant strategies to tackle mcr-mediated polymyxin resistance. 应对 mcr 介导的多粘菌素抗药性的辅助策略。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2024-11-01 DOI: 10.1039/d4md00654b

Madison R Nuske, Junlang Zhong, Renjie Huang, Vijayalekshmi Sarojini, Jack L Y Chen, Christopher J Squire, Mark A T Blaskovich, Ivanhoe K H Leung

引用次数: 0

Design and synthesis of (E)-3-benzylideneindolin-2-one derivatives as potential allosteric inhibitors of Aurora A kinase. 设计和合成(E)-3-苄叉吲哚啉-2-酮衍生物，作为 Aurora A 激酶的潜在异构抑制剂。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2024-11-01 DOI: 10.1039/d4md00373j

YongLai Jiao, Jie Zhong, JinFang Xu, ShaoBo Ning, TaiGang Liang, MingZhu Zhao, Jian Zhang

{"title":"Design and synthesis of (E)-3-benzylideneindolin-2-one derivatives as potential allosteric inhibitors of Aurora A kinase.","authors":"YongLai Jiao, Jie Zhong, JinFang Xu, ShaoBo Ning, TaiGang Liang, MingZhu Zhao, Jian Zhang","doi":"10.1039/d4md00373j","DOIUrl":"10.1039/d4md00373j","url":null,"abstract":"The mitotic kinase Aurora A, a pivotal regulator of the cell cycle, is overexpressed in various cancers and has emerged as one of the most promising targets for anticancer drug discovery. However, the lack of specificity and potential toxicity have impeded clinical trials involving orthosteric inhibitors. In this study, allosteric sites of Aurora A were predicted using the AlloReverse web server. Based on the non-ATP competitive inhibitor Tripolin A and molecular docking information targeting the desired allosteric site 3 of Aurora A, a series of (E)-3-benzylideneindolin-2-one derivatives were designed and synthesized. Compared to Tripolin A, our compounds AK09, AK34 and AK35 have stronger inhibitory effects and can be further investigated as potential allosteric inhibitors. Moreover, the compound AK34 with the strongest inhibitory activity (IC50 = 1.68 μM) has a high affinity for Aurora A (K D = 216 nM). According to the analysis of the structure-activity relationship of the compounds and the results of their molecular docking models, these compounds tend to act on the allosteric site 3 of Aurora A.","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Medicinal chemistry-based perspectives on thiophene and its derivatives: exploring structural insights to discover plausible druggable leads. 基于药物化学的噻吩及其衍生物透视：探索结构洞察力，发现可行的药物线索。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2024-10-30 DOI: 10.1039/d4md00450g

Shikha Thakur, Devendra Kumar, Shivani Jaiswal, Kapil Kumar Goel, Pramod Rawat, Vivek Srivastava, Sonia Dhiman, Hemant R Jadhav, Ashish Ranjan Dwivedi

{"title":"Medicinal chemistry-based perspectives on thiophene and its derivatives: exploring structural insights to discover plausible druggable leads.","authors":"Shikha Thakur, Devendra Kumar, Shivani Jaiswal, Kapil Kumar Goel, Pramod Rawat, Vivek Srivastava, Sonia Dhiman, Hemant R Jadhav, Ashish Ranjan Dwivedi","doi":"10.1039/d4md00450g","DOIUrl":"10.1039/d4md00450g","url":null,"abstract":"Thiophene is a privileged pharmacophore in medicinal chemistry owing to its diversified biological attributes. The thiophene moiety has been ranked 4th in the US FDA drug approval of small drug molecules, with around 7 drug approvals over the last decade. The present review covers USFDA-approved drugs possessing a thiophene ring system. Our analysis reveals that 26 drugs possessing thiophene nuclei have been approved under different pharmacological classes. The review further covers reported thiophene and its substituted analogues with diverse biological activities, including anti-diabetic, anticancer, anti-inflammatory, anticonvulsant, and antioxidant activity. Besides, a section is dedicated to appreciating the implications of structural bioinformatics in drug discovery. Additionally, the manuscript delves into structure-activity relationship studies to explore the chemical groups responsible for eliciting potential therapeutic activities. The review may provide invaluable insights for researchers working with thiophene nuclei in developing novel analogues with greater efficacy and fewer side effects.","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11588141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142732190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis and antifungal evaluation of new azole derivatives containing 1,2,3-triazole. 含有 1,2,3- 三唑的新型唑衍生物的合成和抗真菌评价。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2024-10-29 DOI: 10.1039/d4md00724g

Zhengxiao Huang, Hongjie Chen, Xiao Zhang, Ruirui Wang, Chunyan Hu, Zewei Mao

引用次数: 0

Amides of moronic acid and morolic acid with the tripeptides MAG and GAM targeting antimicrobial, antiviral and cytotoxic effects. 吗啉酸和吗啉酸与三肽 MAG 和 GAM 的酰胺具有抗菌、抗病毒和细胞毒性作用。

IF 4.1 4区医学

RSC medicinal chemistry Pub Date : 2024-10-29 DOI: 10.1039/d4md00742e

Uladzimir Bildziukevich, Lucie Černá, Jana Trylčová, Marie Kvasnicová, Lucie Rárová, David Šaman, Petra Lovecká, Jan Weber, Zdeněk Wimmer

{"title":"Amides of moronic acid and morolic acid with the tripeptides MAG and GAM targeting antimicrobial, antiviral and cytotoxic effects.","authors":"Uladzimir Bildziukevich, Lucie Černá, Jana Trylčová, Marie Kvasnicová, Lucie Rárová, David Šaman, Petra Lovecká, Jan Weber, Zdeněk Wimmer","doi":"10.1039/d4md00742e","DOIUrl":"10.1039/d4md00742e","url":null,"abstract":"A series of amides of selected plant triterpenoids, moronic acid and morolic acid, with the tripeptides MAG and GAM, was designed and synthesized. Two required tripeptides 5 and 10 were synthesized by a step-wise chain elongation of the ethyl esters of either glycine or l-methionine at their N-terminus using Boc-protected amino acids in each step. The tripeptides 5 and 10 were used for the synthesis of 13-23, the derivatives of moronic acid (11) and morolic acid (12), to get a series of amide derivatives of the less frequently studied triterpenoids 11 and 12. The target compounds, and their intermediates, were subjected to an investigation of their antimicrobial, antiviral and cytotoxic activity. Selectivity of the pharmacological effects was found. Generally, the target compounds inhibited only the G+ microorganisms. Compound 16 inhibited Staphylococcus aureus (I = 99.6%; c = 62.5 μM) and Enterococcus faecalis (I = 85%; c = 250 μM). Several compounds showed moderate antiviral effects, both anti-HIV-1, 19 (EC50 = 57.0 ± 4.1 μM, CC50 > 100 μM), 20 (EC50 = 17.8 ± 2.1 μM, CC50 = 41.0 ± 5.2 μM) and 23 (EC50 = 12.6 ± 0.82 μM, CC50 = 38.0 ± 4.2 μM), and anti-HSV-1, 22 (EC50 = 27.7 ± 3.5 μM, CC50 > 100 μM) and 23 (EC50 = 30.9 ± 3.3 μM, CC50 > 100 μM). The target compounds showed no cytotoxicity in cancer cells, however, several of their intermediates were cytotoxic. Compound 21 showed cytotoxicity in HeLa (IC50 = 7.9 ± 2.1 μM), G-361 (IC50 = 8.0 ± 0.6 μM) and MCF7 (IC50 = 8.6 ± 0.2 μM) cancer cell lines, while being non-toxic in normal fibroblasts (BJ; IC50 > 50 μM).","PeriodicalId":21462,"journal":{"name":"RSC medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0