Current medicinal chemistry最新文献

{"title":"Optical Molecular Probes for Imaging and Early Diagnosis of Acute Kidney Injury.","authors":"Junbing He, Zhenzhou Chen, Yao Lin, Qinghua Liu","doi":"10.2174/0109298673299429240607103107","DOIUrl":"https://doi.org/10.2174/0109298673299429240607103107","url":null,"abstract":"<p><p>The kidneys play an irreplaceable role in metabolism and excretion. However, Acute Kidney Injury (AKI) often occurs due to high local concentrations of drugs, inflammation, and trauma. Activated optical probes with excellent detection performance can effectively identify biomarkers in the initial stage of AKI and play an important role in evaluating AKI and preventing the development of diseases. This article summarizes representative design strategies for molecular probes and special diagnostic applications. These molecular probes show great potential in basic research and clinical diagnosis, enabling enhanced images of tissue structure and biomarkers, as well as early diagnosis of AKI. In addition, the difficulties and challenges that optical probes may face in the development and application of AKI are also discussed in this article.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450014","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":"Curcumin Nanoparticles-related Non-invasive Tumor Therapy, and Cardiotoxicity Relieve.","authors":"Yuhang Cheng, Qian Xu, Miao Yu, Chenwei Dang, Limei Deng, Huijun Chen","doi":"10.2174/0109298673305616240610153554","DOIUrl":"https://doi.org/10.2174/0109298673305616240610153554","url":null,"abstract":"<p><p>Non-invasive antitumor therapy can treat tumor patients who cannot tolerate surgery or are unsuitable. However, tumor resistance to non-invasive antitumor therapy and cardiotoxicity caused by treatment seriously affect the quality of life and prognosis of patients. As a kind of polyphenol extracted from herbs, curcumin has many pharmacological effects, such as anti-inflammation, antioxidation, antitumor, etc. Curcumin plays the antitumor effect by directly promoting tumor cell death and reducing tumor cells' invasive ability. Curcumin exerts the therapeutic effect mainly by inhibiting the nuclear factor-κB (NF-κB) signal pathway, inhibiting the production of cyclooxygenase-2 (COX-2), promoting the expression of caspase-9, and directly inducing reactive oxygen species (ROS) production in tumor cells. Curcumin nanoparticles can solve curcumin's shortcomings, such as poor water solubility and high metabolic rate, and can be effectively used in antitumor therapy. Curcumin nanoparticles can improve the prognosis and quality of life of tumor patients by using as adjuvants to enhance the sensitivity of tumors to non-invasive therapy and reduce the side effects, especially cardiotoxicity. In this paper, we collect and analyze the literature of relevant databases. It is pointed out that future research on curcumin tends to alleviate the adverse reactions caused by treatment, which is of more significance to tumor patients.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450012","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":"Hybrid Nanoparticles for Cancer Theranostics: A Critical Review on Design, Synthesis, and Multifunctional Capabilities.","authors":"Saurabh Raka, Sateesh Belemkar, Sankha Bhattacharya","doi":"10.2174/0109298673309011240606095639","DOIUrl":"https://doi.org/10.2174/0109298673309011240606095639","url":null,"abstract":"<p><p>Theranostics, a method that combines targeted therapy and diagnostic imaging, has emerged as a viable route for enhancing cancer treatment, and hybrid nanoparticles (HNPs) are at the forefront of this field. Metallic, polymeric, lipid-based, and silica- based HNPs are studied for targeting and biocompatibility. Using HNPs, chemotherapeutic drugs, small interfering RNA, and therapeutic genes can be given precisely and controlled. This enhances therapeutic efficacy and reduces adverse effects. With fluorescence dyes, MRI contrast agents, and PET tracers, real-time therapy response monitoring is conceivable. A nano platform with therapeutic and diagnostic capabilities holds great promise for personalized medicine and precision oncology. The present study discusses HNPs' biocompatibility, stability, immunogenicity, and long-term biosafety, which are crucial to the clinical translation of cancer theranostics. Further, in this in- -depth investigation, we investigated the design, synthesis, and multifunctional activities of HNPs for use in cancer theranostics.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450013","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":"Virtual Screening, Molecular Dynamics Simulation, and Bioactivity Assessment Validate T13074 as a Dual-Target EGFR/c-Met Inhibitor.","authors":"Dang Fan, Haifeng Dong, Anqi Li, Yuying Zhang, Shiyu Wang, Yuanbiao Tu, Linxiao Wang","doi":"10.2174/0109298673305941240605050450","DOIUrl":"https://doi.org/10.2174/0109298673305941240605050450","url":null,"abstract":"<p><strong>Objectives: </strong>The objective of this study is to identify dual-target inhibitors against EGFR/c-Met through virtual screening, dynamic simulation, and biological activity evaluation. This endeavor is aimed at overcoming the challenge of drug resistance induced by L858R/T790M mutants.</p><p><strong>Methods: </strong>Active structures were gathered to construct sets of drug molecules. Next, property filtering was applied to the drug structures within the compound library. Active compounds were then identified through virtual screening and cluster analysis. Subsequently, we conducted MTT antitumor activity evaluation and kinase inhibition assays for the active compounds to identify the most promising candidates. Furthermore, AO staining and JC-1 assays were performed on the selected compounds. Ultimately, the preferred compounds underwent molecular docking and molecular dynamics simulation with the EGFR and c-Met proteins, respectively.</p><p><strong>Result: </strong>The IC50 of T13074 was determined as 2.446 μM for EGFRL858R/T790M kinase and 7.401 nM for c-Met kinase, underscoring its potential in overcoming EGFRL858R/T790M resistance. Additionally, T13074 exhibited an IC50 of 1.93 μM on the H1975 cell. Results from AO staining and JC-1 assays indicated that T13074 induced tumor cell apoptosis in a concentration-dependent manner. Notably, the binding energy between T13074 and EGFR protein was found to be -90.329 ± 16.680 kJ/mol, while the binding energy with c-Met protein was -139.935 ± 17.414 kJ/mol.</p><p><strong>Conclusion: </strong>T13074 exhibited outstanding antitumor activity both in vivo and in vitro, indicating its potential utility as a dual-target EGFR/c-Met inhibitor. This suggests its promising role in overcoming EGFR resistance induced by the L858R/T790M mutation.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450024","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":"Supplementation of Antioxidants in Chronic Kidney Disease: Clinical Necessity or Wishful Thinking? A Bench to Bedside Translational Research.","authors":"Stefanos Roumeliotis, Ioannis E Neofytou, Konstantia Kantartzi, Panagiotis I Georgianos, Vassilios Liakopoulos","doi":"10.2174/0109298673298815240605071808","DOIUrl":"https://doi.org/10.2174/0109298673298815240605071808","url":null,"abstract":"<p><p>Chronic Kidney Disease (CKD) patients are at increased risk for atherosclerosis, cardiovascular disease (CVD) and progression to end stage kidney disease (ESKD). This heavy CVD risk cannot be solely at-tributed to traditional Framingham risk factors. Oxidative stress (OS), defined as the disruption of balance between prooxidants and antioxidants in favor of the former, has emerged as a novel risk factor for CVD and CKD progression. Specifically, lipid peroxidation has been identified as a trigger for endothelial dys-function, the first step towards atherogenesis and protein oxidation has been associated with CKD progres-sion. The oxidation of proteins and lipids starts early in CKD, increases gradually with disease progression and is further exacerbated in ESKD, due to dialysis related factors. In order to counteract the deleterious effects of free radicals and thereby ameliorate, or delay, CV disease and progression of CKD, exogenous administration of antioxidants has been proposed. Here, we attempt to summarize existing data from ex-perimental and clinical studies that test antioxidants for their possible beneficial effects against CVD and CKD progression such as vitamins E and C, statins, omega-3 fatty acids, trace elements, polyphenols and N-acetylcysteine. </p>.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442277","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 Anthocyanins: Unveiling Sources, Analytical Techniques, and Biological Activities.","authors":"Ashutosh Agarwal, Niyatee Thakor, Lata Manani, Parixit Prajapati, Gehan M Elossaily, Bhupendra G Prajapati","doi":"10.2174/0109298673310694240605074429","DOIUrl":"https://doi.org/10.2174/0109298673310694240605074429","url":null,"abstract":"<p><p>Anthocyanins (ANCs) are obtained from pigmented foods like blueberry, strawberry, and red cabbage and are phenolic compounds belonging to the flavonoids family. ANCs have garnered significant attention in recent years due to their diverse biological activities and potential health benefits. This comprehensive review presents a holistic exploration of anthocyanins, spanning from their chemical structure and biosynthesis pathways to the myriad analytical techniques employed for their identification and quantification. Furthermore, the rich tapestry of plant sources yields anthocyanins is delved into, highlighting their incorporation into various pharmaceutical formulations. This review aims to provide a comprehensive synthesis of current knowledge on anthocyanins, spanning from their origins in nature to their multifaceted pharmacological activities and innovative pharmaceutical applications. </p>.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442248","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":"The Role and Effect of Music Therapy in Combination Therapy for Cancer Management.","authors":"Peijin Liu, Shigao Huang","doi":"10.2174/0109298673307490240614053104","DOIUrl":"https://doi.org/10.2174/0109298673307490240614053104","url":null,"abstract":"<p><p>Cancer is one of the major diseases that harm human health. Tumor patients face a series of problems, including tumor disease symptoms, side effects of treatment, potential complications of illness, financial problems, and even the threat of death. The majority of patients are aware of these problems. It often manifests as fear, anxiety, anger, complaining, and depression. This leads to the generation of negative emotions, such as insanity and loneliness. These complications, such as feelings and isolation, seriously affect the quality of life of patients. Conventional treatments such as chemotherapy and radiotherapy cause some side effects and adverse reactions or difficulty in controlling some symptoms generated by the tumor itself. Therefore, some complementary and alternative medicines based on conventional cancer treatment have been added. In recent years, music nursing, as a non-traumatic and psychological therapy, has been applied to cancer patients, which plays a good role in improving their negative emotions and improving their quality of life. Moreover, this review summarizes the evolution of music therapy (MT), exploring the mechanism of MT and its clinical application in cancer management. In addition, some challenges and perspectives e.g., artificial intelligence applications for music therapy, are discussed. This work aims to encourage the broader application of MT for cancer patients to improve the survival experience of cancer patients, which is low cost, easy to implement, low risk, and efficient method.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442278","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":"Determination of Inhibitory Effect of PKM2 Enzyme and Antitumoral Activity of Novel Coumarin-Naphthoquinone Hybrids.","authors":"Amanda de A Borges, Gabriel Ouverney, Afonso T S Arruda, Amanda V Ribeiro, Ruan C B Ribeiro, Acácio S Souza, Anna Carolina C da Fonseca, Lucas N Nicolau de Queiroz, Elan C P de Almeida, Bruno Pontes, Vitor W Rabelo, Vitor F Ferreira, Paula A Abreu, Fernando de C da Silva, Luana da S M Forezi, Bruno K Robbs","doi":"10.2174/0109298673298471240605072658","DOIUrl":"https://doi.org/10.2174/0109298673298471240605072658","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) represents the primary form of oral cancer, posing a significant global health threat. The existing chemotherapy options are accompanied by notable side effects impacting patient treatment adherence. Consequently, the exploration and development of novel substances with enhanced anticancer effects and fewer side effects have become pivotal in the realms of biological and chemical science.</p><p><strong>Objective: </strong>This work presents the pioneering examples of naphthoquinone-coumarin hybrids as a new category of highly effective cytotoxic substances targeting oral squamous cell carcinoma (OSCC).</p><p><strong>Methods: </strong>Given the significance of both naphthoquinones and coumarins as essential pharmacophores/ privileged structures in the quest for anticancer compounds, this study focused on the synthesis and evaluation of novel naphthoquinones/coumarin hybrids against oral squamous cell carcinoma.</p><p><strong>Results: </strong>By several in vitro, in silico, and in vivo approaches, we demonstrated that compound 6e was highly cytotoxic against OSCC cells and several other cancer cell types and was more selective than current chemotherapeutic drugs (carboplatin) and the naphthoquinone lapachol. Furthermore, compound 6e was non-hemolytic and tolerated in vivo at 50 mg/kg with an LD50 of 62.5 mg/kg. Furthermore, compound 6e did not induce apoptosis and cell cycle arrest but led to intracellular vesicle formation with LC3 aggregation in autophagosomes, suggesting an autophagic cell death. Additionally, 6e had a high-affinity potential for PKM2 protein, higher than the known ligands, such as lapachol or shikonin, and was able to inhibit this enzyme activity in vitro.</p><p><strong>Conclusion: </strong>We assert that compound 6e shows promise as a potential lead for a novel chemotherapeutic drug targeting OSCC, with potential applicability to other cancer types.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327322","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":"Relationship between Cellular Oxygen Consumption and Atherosclerosis-Associated Mitochondrial Mutations (Variants of the Mitochondrial Genome).","authors":"Alexander N Orekhov, Vasily V Sinyov, Mikhail Y Vyssokikh, Ludmila Manukhova, Maria V Marey, Plamena R Angelova, Andrey V Omelchenko, Andrey Y Vinokurov, Zukhra B Khasanova, Igor A Sobenin","doi":"10.2174/0109298673302002240605092523","DOIUrl":"https://doi.org/10.2174/0109298673302002240605092523","url":null,"abstract":"<p><strong>Background: </strong>Mitochondria are the main sites of cellular aerobic energy production through conjugation of respiration and oxidative phosphorylation. We have recently discovered mutations (genome variants) of mitochondrial DNA (mtDNA) associated with atherosclerosis. We have then investigated the possible mechanisms underlying such association and the role of mitochondrial mutations in atherogenesis. Mitochondrial dysfunction is a known component of the pathogenesis of chronic human diseases, including atherosclerosis.</p><p><strong>Objective: </strong>The aim of the study was to explore whether there is a relationship between cellular oxygen consumption and atherosclerosis-associated mitochondrial mutations. The study of mitochondrial respiration abnormalities can help to understand the role of mtDNA mutations in pathology.</p><p><strong>Method: </strong>By using the polarographic method with Clark electrode, we tested the possibility of respiration impairment in permeabilized cells carrying the tested mtDNA variants using the cybrid (cytoplasmic hybrid) lines. Mitochondria introduced in the cybrid lines were obtained from atherosclerotic patients that differed in the profile of mtDNA mutations, which made it possible to compare the degree of mtDNA mutation load with the rate of oxygen consumption by cybrid cells.</p><p><strong>Results: </strong>It was found that three of the studied mutations were individually associated with impaired respiration. Besides, some combinations of two specific mutations have a high probability of being associated with altered oxygen consumption. As a result, eight mutations were identified, individually or paired combinations of which were associated with high or low rates of cellular respiration, significantly different from control cells.</p><p><strong>Conclusion: </strong>The observed effect may be involved in the pathogenesis of atherosclerosis. The study of mtDNA mutations associated with atherosclerosis can help reveal pharmacological targets for the development of novel therapies.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327324","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":"Predictive Analysis of Yi-Gai-San's Multifaceted Mechanisms for Tremor-Dominant Parkinson's Disease via Network Pharmacology and Molecular Docking Validation.","authors":"Chih-Ting Lin, Lung-Yuan Wu, Fan-Shiu Tsai","doi":"10.2174/0109298673291838240311075415","DOIUrl":"https://doi.org/10.2174/0109298673291838240311075415","url":null,"abstract":"<p><strong>Introduction: </strong>Based on comprehensive network-pharmacology and molecular docking analysis, this study was intended to unveil the multiple mechanisms of Yi-- Gai-San (YGS) in treating the tremor-dominant subtype of Parkinson's disease (PDDT). The compounds of YGS were meticulously analyzed, selected, and standardized with references to their pharmacological attributes. Its components included Gouteng (Uncaria rhynchophylla), Chaihu (Radix Bupleuri), Chuanxiong (Chuanxiong Rhizoma), Danggui (Angelicae Sinensis Radix), Fuling (Wolfiporia extensa), Baizhu (Atractylodis macrocephalae rhizoma), and Gancao (Licorice, Glycyrrhizae radix).</p><p><strong>Method: </strong>We identified 75 active compounds within YGS. From these, we predicted 110 gene targets, which exhibited a direct association with PD-DT. PPI network results highlighted core target proteins, including TP53, SLC6A3, GAPDH, MAOB, AKT, BAX, IL6, BCL2, PKA, and CASP3. These proteins potentially alleviate PD-DT by targeting inflammation, modulating neuronal cell apoptosis, and regulating the dopamine system. Furthermore, GO and KEGG enrichment analyses emphasized that YGS might influence various mechanisms, such as the apoptotic process, mitochondrial autophagy, Age- Rage signaling, and dopaminergic and serotonergic synapses. The core proteins from the PPI analysis were selected for the docking experiment.</p><p><strong>Result: </strong>The docking results demonstrated that the most stable ligand-receptor conformations were kaempferol with CASP3 (-9.5 kcal/mol), stigmasterol with SLC6A3 (-10.5 kcal/mol), shinpterocarpin with BCL2L1 (-9.6 kcal/mol), hirsutine with MAOB (-9.7 kcal/mol), hederagenin with PRKACA (-9.8 kcal/mol), and yatein with GAPDH (-9.8 kcal/mol). These results provide us with research objectives for future endeavors in extracting single compounds for drug manufacturing or in-depth studies on drug mechanisms.</p><p><strong>Conclusion: </strong>From these computational findings, we suggested that YGS might mitigate PD-DT via \"multi-compounds, multi-targets, and multi-pathways.\"</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327323","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}