Current medicinal chemistry最新文献

{"title":"Pre-Stage Oral Cancer Biomarker Analysis in Non-invasive Salivary Samples: A Way to Go.","authors":"Periasamy Anbu, Subash C B Gopinath","doi":"10.2174/0109298673337297240923062829","DOIUrl":"https://doi.org/10.2174/0109298673337297240923062829","url":null,"abstract":"","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361305","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}

{"title":"Recent Advancements in the Delivery of Therapeutic Agents Targeting RNA-dependent RNA Polymerase of SARS-CoV-2.","authors":"Kalpesh Mahajan, Dipika Pawar, Sankha Bhattacharya","doi":"10.2174/0109298673312897240919111317","DOIUrl":"https://doi.org/10.2174/0109298673312897240919111317","url":null,"abstract":"<p><p>This study aimed to undertake a complete evaluation and analysis of all known data on RNA-dependent RNA polymerase (RdRp) inhibitors, concentrating on their safety, efficacy, and current improvements in the delivery of therapeutic drugs targeting RdRp of SARS-CoV-2. The work has attempted to emphasise the necessity for future research into the development of nanocarrier-based targeted drug delivery methods for RdRp inhibitors in the treatment of COVID-19. In December 2019, a novel SARS-- CoV-2 strain was discovered in Wuhan, China. SARS-CoV-2 is transferable among humans and has caused a global pandemic. The rapid global outbreak of SARS-CoV-2 and numerous deaths caused because of coronavirus disease (COVID-19) prompted the World Health Organization to announce a pandemic on March 12, 2020. COVID-19 is becoming a key concern that has a significant impact on an individual's life status. RdRp inhibitors are major pharmaceutical agents used in the treatment of COVID-19, which have various undesirable side effects, a greater risk of recurrence, lower bioavailability, as well as a lack of targeted therapy. Hence, the present article has provided a review on all known data on RdRp inhibitors, safety, and efficacy, and recent advances in the delivery of therapeutic agents targeting RdRp of SARS-CoV-2. An analysis has been done using a scientific data search engine, such as the National Center for Biotechnology Information (NCBI/PubMed), Science Direct, Google Scholar, WIPO, Lens, etc. The information has emphasized the need for more research into the safety, efficacy, and development of nanocarrier-based targeted drug delivery systems for RdRp inhibitors in the treatment of COVID-19.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343332","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}

{"title":"Neuroimmune Interactions in Stress and Depression: Exploring the Molecular and Cellular Mechanisms within the Neuroinflammation-depression Nexus.","authors":"Alexey Sarapultsev, Evgenii Gusev, Valeriy Chereshnev, Maria Komelkova, Desheng Hu","doi":"10.2174/0109298673320710240920055041","DOIUrl":"https://doi.org/10.2174/0109298673320710240920055041","url":null,"abstract":"<p><strong>Background: </strong>The escalating global burden of stress and depression underscores an urgent need to unravel their complex interrelationships and underlying mechanisms. This investigation delves into the intricate dynamics between stress and depression, spotlighting the Neuroimmunoinflammatory Stress Model (NIIS), which elucidates the pivotal role of cellular and molecular pathways in mediating these conditions.</p><p><strong>Methods: </strong>Through an exhaustive review of literature spanning epidemiology, neurobiology, and psychoneuroimmunology, this study synthesizes the current understanding of stress and depression. It accentuates the definitional scopes, interplay, and intricacies of the NIIS model, which integrates neuroimmune-inflammatory responses into the conceptual framework of the stress-depression interaction.</p><p><strong>Results: </strong>By identifying stress as a multifactorial reaction to perceived adversities and depression as a manifestation of prolonged stress exposure, our analysis foregrounds the NIIS model. This paradigmatic model reveals the transition from normal stress responses to pathological neuroinflammatory pathways, highlighting neurotransmitter imbalances, disruptions in neuronal and glial homeostasis, and ensuing low-grade neuroinflammation as key factors in the pathogenesis of depression under chronic stress conditions. The NIIS model identifies prolonged cellular pro-inflammatory stress of neurons and microglia as a fundamental pathological subsystem of many neuropsychiatric disorders. In turn, neuroinflammation and associated neurodegenerative processes are complications of chronic psychoemotional stress, which can clinically manifest as depression.</p><p><strong>Conclusions: </strong>The NIIS model views depression as the terminal stage of chronic stress, pathogenetically linked to latent neuroinflammation. This insight not only advances our understanding of their etiopathogenesis but also paves the way for developing precise therapeutic interventions.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343330","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}

{"title":"Phenolic Glycoside Monomer from Reed Rhizome Inhibits Melanin Production via PI3K-Akt and Ras-Raf-MEK-ERK Pathways.","authors":"Meijun Pang, Hong Yao, Kechen Bao, Ruitian Xu, Rongjiao Xi, Rui Peng, Hui Zhi, Kuo Zhang, Runnan He, Yunfei Du, Yanfang Su, Xiuyun Liu, Dong Ming","doi":"10.2174/0109298673341645240919072455","DOIUrl":"https://doi.org/10.2174/0109298673341645240919072455","url":null,"abstract":"<p><strong>Introduction: </strong>Melanogenesis, the process responsible for melanin production, is a critical determinant of skin pigmentation. Dysregulation of this process can lead to hyperpigmentation disorders.</p><p><strong>Method: </strong>In this study, we identified a novel <i>Reed Rhizome</i> extract, (1'S, 2'S)-syringyl glycerol 3'-O-β-D-glucopyranoside (compound 5), and evaluated its anti-melanogenic potential in zebrafish models and <i>in vitro</i> assays. Compound 5 inhibited melanin synthesis by 36.66% ± 14.00% and tyrosinase <i>in vivo</i> by 48.26% ± 6.94%, surpassing the inhibitory effects of arbutin. Network pharmacological analysis revealed key targets, including HSP90AA1, HRAS, and PIK3R1, potentially involved in the anti-melanogenic effects of compound 5.</p><p><strong>Results: </strong>Molecular docking studies supported the interactions between compound 5 and these targets. Further, gene expression analysis in zebrafish indicated that compound 5 up-regulates <i>hsp90aa1.1, hrasa,</i> and <i>pik3r1,</i> and subsequently down-regulating <i>mitfa,</i> tyr, and tyrp1, critical genes in melanogenesis.</p><p><strong>Conclusion: </strong>These findings suggest that compound 5 inhibits melanin production <i>via</i> PI3K-Akt and Ras-Raf-MEK-ERK signaling pathways, positioning it as a promising candidate for the treatment of hyperpigmentation.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343331","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}

{"title":"Exploring the Therapeutic Potential of Coumarin-thiazolotriazole Pharmacophores for SARS-CoV-2 Spike Protein through In-vitro and In-silico Evaluation.","authors":"Saeed Ullah, Atta Ullah, Muhammad Waqas, Sobia Ahsan Halim, Imtiaz Khan, Sadeeq Ur Rehman, Magda H Abdellattif, Samreen Soomro, Aliya Ibrar, Hamdy Kashtoh, Ajmal Khan, Ahmed Al-Harrasi","doi":"10.2174/0109298673323284240911052131","DOIUrl":"https://doi.org/10.2174/0109298673323284240911052131","url":null,"abstract":"<p><strong>Introduction: </strong>The pandemic caused by SARS-CoV-2 significantly impacted human life around the globe. Numerous unexpected modifications of the SARS-CoV-2 genome have resulted in the emergence of new types and have caused great concern globally.</p><p><strong>Method: </strong>Inhibitory effects of bioactive phytochemicals derived from natural and synthetic sources are promising for pathogenic viruses. in vitro and in silico techniques were used in the current study to identify novel inhibitors of coumarin clubbed thiazolo[3,2-b][1,2,4]triazoles against the SARS-CoV-2 spike protein.</p><p><strong>Result: </strong>Interestingly, all the tested molecules demonstrated substantial inhibition of spike protein with 91.81-57.90% inhibition. The spike protein was remarkably inhibited by compounds 6k (91.83%), 6j (89.75%), 6m (87.69%),6i (86.60%), 6l (85.40%), 6h (84.70%), 6l (84.70%), 6g (83.40%), 6b (82.60%), 6f (81.90%), while compounds 6d 6a, 6c, and 6e exhibited significant activity against spike protein with 79.60%, 77.10%, 75.30%, and 57.90% inhibition, respectively. The binding mechanism of these novel inhibitors with spike protein was deduced in silico, which reflects that the active molecules firmly bind with the receptor binding domain (RBD) of spike protein, thereby inhibiting its function.</p><p><strong>Conclusion: </strong>The combined in vitro and in silico investigations unfold the therapeutic potential of coumarin-thiazolotriazole scaffolds in the treatment of SARS-CoV-2 infection.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343328","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}

{"title":"Exploring the Potential of Terpenoids as a Possible Treatment for Cancer: Structure-Activity Relationship and Mechanistic Studies.","authors":"Arshdeep Singh, Rabin Debnath, Anjali Sharma, Aniket Saini, Kushal Seni, Viney Chawla, Pooja A Chawla","doi":"10.2174/0109298673315133240830055507","DOIUrl":"https://doi.org/10.2174/0109298673315133240830055507","url":null,"abstract":"<p><p>Cancer stands as a significant global health challenge due to its mortality rates and the complexities involved in its treatment. Addressing issues, such as metastasis, recurrence, chemoresistance, and treatment-related toxicity, remains pivotal in cancer therapy advancement. Therefore, exploration of novel therapeutic agents has emerged as a priority. As the risk of cancer continues to rise, effective measures must be taken to combat it. One promising approach is to explore natural remedies, such as terpenoids, which have demonstrated anticancer activity. Utilizing terpenoids could aid in the development of potent compounds to fight cancer. By studying the structural makeup of various terpenoid derivatives from previous research, we can identify which structural groups are essential for their anticancer activity. This understanding of the structure-activity relationship is crucial for developing new, effective anticancer agents based on terpenoids. Terpenoids, a diverse class of plant-derived secondary metabolites composed of multiple isoprene units, have garnered attention for their potential anticancer and pharmacological qualities. Some terpenoids exhibit notable anticancer effects by concentrating on several stages of cancer development. They show promise in blocking the initiation of early carcinogenesis by the induction of cell cycle arrest, the inhibition of cancer cell differentiation, and the induction of apoptosis. This study delves into the investigation of specific terpenoids showcasing promising anticancer activity against prevalent malignancies, including breast, colon, ovarian, and lung cancers. The study also explores the relationship between the structure and activity of these compounds, which sheds light on how effective they are against a variety of cancer cell types. The comprehensive discussion centres on elucidating terpenoids with substantial potential for combating diverse cancer types, offering insights into their structural features and promising anticancer mechanisms.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343327","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}

{"title":"Discovery of Small Molecule Inhibitors Targeting CTNNB1 (β-catenin) for Endometrial cancer: Employing 3D QSAR, Drug-Likeness Assessment, ADMET Predictions, Molecular Docking and Simulation.","authors":"Israr Fatima, Abdur Rehman, Peng Wang, Zhijie He, Mingzhi Liao","doi":"10.2174/0109298673307257240826111754","DOIUrl":"https://doi.org/10.2174/0109298673307257240826111754","url":null,"abstract":"<p><strong>Background: </strong>Endometrial carcinoma (EC) is a type of cancer that originates in the lining of the uterus, known as the endometrium. It is associated with various treatment options such as surgery, radiation therapy, chemotherapy, and hormone therapy, each presenting unique challenges and limitations. Beta-catenin, a protein involved in the development and progression of several cancers, including EC, plays a crucial role. Abnormal beta-catenin signaling is often linked to the emergence of specific EC subtypes, affecting tumor growth and invasion.</p><p><strong>Objectives: </strong>The study's objective is to identify compounds targeting the beta-catenin protein for treating endometrial cancer (EC) using in silico drug design. Our approach includes molecular docking to evaluate binding affinities, ADME profiling for pharmacokinetic properties, toxicity assessments, and molecular dynamics simulations to assess compound stability and interactions.</p><p><strong>Methods: </strong>Approximately one thousand anti-cancer phytochemicals were sourced from PubChem and subjected to molecular docking simulations against the beta-catenin protein. The compounds were evaluated based on their binding affinities, with the top five selected for further analysis. These five molecules underwent toxicity and ADME profiling. The Prediction of Activity Spectra for Substances (PASS) tool was used to identify compounds targeting CTNNB1. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were employed to establish quantitative structure-activity relationship (QSAR) models for the five CTNNB1 antagonist molecules.</p><p><strong>Results: </strong>The selected five compounds, namely Pazopanib, Binimetinib, Telatinib, 4-(2,3-Dihydrobenzo[ b][1,4]dioxin-6-yl)-3-((5-nitrothiazol-2-yl)thio)-1H-1,2,4-triazol-5(4H)-one, and Ribavirin, demonstrated efficacy against CTNN1. MD simulations of the docked complexes confirmed the stability of these drugs in binding to the target protein. All five molecules showed promising safety and effectiveness profiles according to their ADME and toxicity evaluations.</p><p><strong>Conclusion: </strong>Through a comprehensive screening process employing in silico drug design methods, this study successfully identified five potential human anticancer drug candidates targeting the beta-catenin protein. These findings offer a foundation for further experimental validation and development towards the treatment of EC.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343326","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}

{"title":"Vincristine in Cancer Therapy: Mechanisms, Efficacy, and Future Perspectives.","authors":"Nitika Garg, Joviana Farhat, Sanchit Dhankhar, Samrat Chauhan, Rajni Bala, Reecha Madaan, Himanshu Sharma, Monika Saini, Thakur Gurjeet Singh, Afaf Ahmed Aldahish, Zainab Almarhoon, Basem Al-Omari, Javad Sharifi-Rad","doi":"10.2174/0109298673319496240911060138","DOIUrl":"https://doi.org/10.2174/0109298673319496240911060138","url":null,"abstract":"<p><p>Cancer remains one of the predominant causes of mortality globally, accounting for over 10 million deaths each year. Despite advancements in medical treatments, the challenge of resistance and treatment failure persists, necessitating innovative approaches. Traditional cancer treatments include surgery, chemotherapy, radiation therapy, and pharmaceutical therapy. In recent years, significant attention has been directed towards plant-derived compounds as potential chemotherapeutic agents and preventive measures against cancer. Vincristine, a distinguished alkaloid derived from plant secondary metabolites, has shown considerable efficacy in cancer treatment. As a member of the antimitotic class of compounds, vincristine disrupts the cell cycle by causing aberrations in microtubule function, thereby inhibiting cell division and proliferation. This mechanism of action positions vincristine as a potent agent against various malignancies. Its role in combination therapy is crucial, as it is often administered in low doses alongside other chemotherapeutic agents to enhance its efficacy and reduce the risk of resistance. In the realm of medicinal chemistry, understanding vincristine's molecular mechanism is paramount. Detailed investigations into its interaction with cellular components can provide insights into its antineoplastic properties. This review aimed to elucidate vincristine's mechanism of action and structure-activity relationship, and summarize current in vitro and in vivo studies evaluating its efficacy. Moreover, it discusses innovative strategies, including nanotechnology-based delivery systems, designed to optimize vincristine formulations. These advanced delivery systems aim to improve bioavailability, target specificity, and minimize systemic toxicity. This comprehensive analysis underscores the critical role of vincristine in contemporary cancer treatment and highlights future directions for research and development in this field.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343333","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}

{"title":"Morpholine-tethered Novel Hydrazones as Promising Non-peptidic Prolyl Oligopeptidase (POP) Inhibitors: Synthesis In Vitro and In Silico Studies.","authors":"Urwa Khalid, Noor Fatima, Saeed Ullah, Sobia Ahsan Halim, Ajmal Khan, Suraj N Mali, Attalla F El-Kott, Mohammed A AlShehri, Hamdy Kashtoh, Ahmed Al-Harrasi, Zahid Shafiq","doi":"10.2174/0109298673304532240911070202","DOIUrl":"https://doi.org/10.2174/0109298673304532240911070202","url":null,"abstract":"<p><strong>Introduction: </strong>Prolyl oligopeptidase (POP) is a pivotal druggable target implicated in diverse biological processes and linked to the development of various ailments, including neurodegenerative disorders. While conventional peptide-based inhibitors have been a centerpiece, their limitations, such as restricted bioavailability, necessitate exploration of non-peptidic inhibitors for their therapeutic potential.</p><p><strong>Method: </strong>This study focuses on designing, synthesizing, and assessing morpholine-based hydrazones targeting the catalytic serine residue of POP. The hydrazones (5a-o), reported as moderately potent analogs compared to the renowned Z-Pro-Prolinal, demonstrated in vitro POP inhibition with IC50 values ranging from 13.60 ± 2.51 to 36.51 ± 1.82 μM. The derivative 5h, with an IC50 of 13.60 ± 2.51 μM, emerged as the most potent inhibitor.</p><p><strong>Results: </strong>Moreover, the in vitro kinetic study of compound 5h indicated that it exhibited concentration-dependent type of inhibition. in silico docking studies of 5h revealed robust interactions in the POP enzyme's active site, yielding a docking score of -6.30 Kcal/- mol, consistent with experimental results.</p><p><strong>Conclusion: </strong>All findings underscored the potential of synthesized derivatives for drug development.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343329","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}

{"title":"HPV-16 Biosensing Systems for Diagnosing Early Stages and Monitoring Oropharyngeal Cancer.","authors":"Thangavel Lakshmipriya","doi":"10.2174/0109298673333806240911073447","DOIUrl":"https://doi.org/10.2174/0109298673333806240911073447","url":null,"abstract":"","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307339","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}