Current topics in medicinal chemistry最新文献

{"title":"Targeted Cancer Stem Cell Therapeutics: An Update.","authors":"Naurin Fatima, Mohammad Umar, Subiya Ambreen, Mohd Shaququzzaman, Mohammad Mumtaz Alam, Ruhi Ali","doi":"10.2174/0115680266275014240110071351","DOIUrl":"https://doi.org/10.2174/0115680266275014240110071351","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) have become a key player in the growth of tumors, the spread of cancer, and the resistance to therapeutic interventions. Targeting these elusive cell populations has the potential to fundamentally alter cancer treatment plans. CSCs, also known as tumor-initiating cells (TICs), are thought to play a role in both medication resistance and cancer recurrence. This is explained by their capacity to regenerate themselves and change into different kinds of cancer cells. Due to their higher expression of ATP-binding cassette (ABC) membrane transporters, enhanced epithelial to mesenchymal (EMT) characteristics, improved immune evasion, activation of survival signaling pathways, and improved DNA repair mechanisms, CSCs exhibit extraordinary resistance to therapies. This comprehensive analysis delves into advancements in the domain of Targeted Cancer Stem Cell Therapeutics, concentrating on unraveling the distinctive traits of CSCs and the therapeutic methods devised to eliminate them.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139574867","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 Mushroom Albatrellus confluens: A Minireview on Phytochemistry, Biosynthesis, Synthesis and Pharmacological Activities.","authors":"Ninh The Son, Chu Anh Van","doi":"10.2174/0115680266291757240124093756","DOIUrl":"https://doi.org/10.2174/0115680266291757240124093756","url":null,"abstract":"<p><strong>Background: </strong>Albatrellus confluens is one of the representative species in the Polyporaceae family. Its major mero terpenoid grifolin and related compounds have the potential for drug applications.</p><p><strong>Objective: </strong>The current study aims to briefly provide an insightful view of the phytochemistry, biosynthesis, synthesis, and pharmacology of A. confluens metabolites.</p><p><strong>Methods: </strong>Data collection was performed using electronic resources, e.g., Google Scholar, PubMed, and Sci-Finder from the 1990s to the present, while Albatrellus confluens is the most meaningful keyword in the search for publications. The Latin name Albatrellus confluens (Alb. & Schwein.) Kotl. & Pouzar is in accordance with the name listing on www.mycobank.org.</p><p><strong>Results: </strong>By chromatography column procedures, it indicated that A. confluens species was associated with the presence of 57 secondary metabolites, in which nitrogenous compounds, meroterpenoids, polyene pyrones, and polyesters can be seen as the main phytochemical classes. L-isoleucine was the parent molecule in biosynthetic and synthetic steps of A. confluens nitrogenous compounds. Numerous experiments revealed that A. confluens isolated compounds have a variety of pharmacological activities, such as anticancer, anti-inflammatory, vasorelaxant, and neuroprotective and skin whitening activities. Some isolates become potential cancer inhibitors. Grifolin induced apoptosis and promoted cell cycle arrest in A2780 ovarian cancer cells via the inactivation of the ERK1/2/Akt signaling pathway. Grifolic acid caused osteosarcoma cancer cell deaths by inhibiting NADH generation and ATP production without obvious toxicity. Neoalbaconol caused apoptosis and necroptosis in mice bearing nasopharyngeal C666-1 cancer cells via PDK1-PI3K/Akt signaling inhibition.</p><p><strong>Conclusion: </strong>The continuation of chromatographic separation and biomedical research is expected. Modern biological assays for explaining the pharmacological values of A. confluens constituents are warranted. Toxicological and pharmacokinetic assessments are urgently needed.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570124","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":"Neurotrophic Factors in Cannabis-induced Psychosis: An Update.","authors":"Valerio Ricci, Domenico de Berardis, Giovanni Martinotti, Giuseppe Maina","doi":"10.2174/1568026623666230829152150","DOIUrl":"10.2174/1568026623666230829152150","url":null,"abstract":"<p><strong>Background: </strong>Cannabis is the most widely used illicit substance. Numerous scientific evidence confirm the strong association between cannabis and psychosis. Exposure to cannabis can induce the development of psychosis and schizophrenia in vulnerable individuals. However, the neurobiological processes underlying this relationship are unknown. Neurotrophins are a class of proteins that serve as survival factors for central nervous system (CNS) neurons. In particular, Nerve Growth Factor (NGF) plays an important role in the survival and function of cholinergic neurons while Brain Derived Neurotrophic Factor (BDNF) is involved in synaptic plasticity and the maintenance of midbrain dopaminergic and cholinergic neurons. Glial Cell Derived Neurotrophic Factor (GDNF) promotes the survival of midbrain dopaminergic neurons and Neuregulin 1 (NrG- 1) contributes to glutamatergic signals regulating the N-methyl-D-aspartate (NMDA). They have a remarkable influence on the neurons involved in the Δ-9-THC (tethra-hydro-cannabinol) action, such as dopaminergic and glutamatergic neurons, and can play dual roles: first, in neuronal survival and death, and, second, in activity-dependent plasticity.</p><p><strong>Methods: </strong>In this brief update, reviewing in a narrative way the relevant literature, we will focus on the effects of cannabis on this class of proteins, which may be implicated, at least in part, in the mechanism of the psychostimulant-induced neurotoxicity and psychosis.</p><p><strong>Conclusion: </strong>Since altered levels of neurotrophins may participate in the pathogenesis of psychotic disorders which are common in drug users, one possible hypothesis is that repeated cannabis exposure can cause psychosis by interfering with neurotrophins synthesis and utilization by CNS neurons.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"1757-1772"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10167657","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":"Traditional uses, Phytochemistry, Pharmacology, and Toxicology of the Genus <i>Artemisia L. (Asteraceae)</i>: A High-value Medicinal Plant.","authors":"Manzoor Hussain, Rakesh Kr Thakur, Jabeena Khazir, Sajad Ahmed, Mohammad Imtiyaj Khan, Praveen Rahi, Latif Ahmad Peer, Pragadheesh Vppalayam Shanmugam, Satwinderjeet Kaur, Soom Nath Raina, Zafar Ahmad Reshi, Deepmala Sehgal, Vijay Rani Rajpal, Bilal Ahmad Mir","doi":"10.2174/1568026623666230914104141","DOIUrl":"10.2174/1568026623666230914104141","url":null,"abstract":"<p><p>Biologically active secondary metabolites, essential oils, and volatile compounds derived from medicinal and aromatic plants play a crucial role in promoting human health. Within the large family Asteraceae, the genus <i>Artemisia</i> consists of approximately 500 species. <i>Artemisia</i> species have a rich history in traditional medicine worldwide, offering remedies for a wide range of ailments, such as malaria, jaundice, toothache, gastrointestinal problems, wounds, inflammatory diseases, diarrhoea, menstrual pains, skin disorders, headache, and intestinal parasites. The therapeutic potential of <i>Artemisia</i> species is derived from a multitude of phytoconstituents, including terpenoids, phenols, flavonoids, coumarins, sesquiterpene lactones, lignans, and alkaloids that serve as active pharmaceutical ingredients (API). The remarkable antimalarial, antimicrobial, anthelmintic, antidiabetic, anti-inflammatory, anticancer, antispasmodic, antioxidative and insecticidal properties possessed by the species are attributed to these APIs. Interestingly, several commercially utilized pharmaceutical drugs, including arglabin, artemisinin, artemether, artesunate, santonin, and tarralin have also been derived from different <i>Artemisia</i> species. However, despite the vast medicinal potential, only a limited number of <i>Artemisia</i> species have been exploited commercially. Further, the available literature on traditional and pharmacological uses of <i>Artemisia</i> lacks comprehensive reviews. Therefore, there is an urgent need to bridge the existing knowledge gaps and provide a scientific foundation for future <i>Artemisia</i> research endeavours. It is in this context, the present review aims to provide a comprehensive account of the traditional uses, phytochemistry, documented biological properties and toxicity of all the species of <i>Artemisia</i> and offers useful insights for practitioners and researchers into underutilized species and their potential applications. This review aims to stimulate further exploration, experimentation and collaboration to fully realize the therapeutic potential of <i>Artemisia</i> in augmenting human health and well-being.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"301-342"},"PeriodicalIF":3.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10241750","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":"Gamma Secretase as an Important Drug Target for Management of Alzheimer's Disease: A Comprehensive Review.","authors":"Fady Tadros Hakem, Youstina Farid Fouad, Reem K Arafa","doi":"10.2174/0115680266259174231006070637","DOIUrl":"10.2174/0115680266259174231006070637","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurological disease that affects the memory. AD has been attributed to the aggregations of amyloid-β (Aβ) peptides which result in the formation of plaques that block the neuron-transferring process done by the brain memory cells. These plaques are formed upon cleavage of Amyloid Precursor Protein (APP) by Gamma-Secretase (GS). GS protein has around 141 substrates, the important two are APP and Notch. Considering one of the hot spots in AD research, we focused on GS and its relation to AD. Moreover, a lot of research was done on beta-secretase and drugs were developed to target it however, few drugs are established for GS. GS contains four subunits: Presenilin (PS), PEN-2, Nicastrin, and APH-1. The catalytic subunit is PS, which contains the active site for substrate binding, as well as the allosteric and docking sites. Both PEN-2 and APH-1 are regulators for the stability and activity of GS. Nicastrin, helps the substrates bind to the PS. Additionally, the role of the immuno-protein named \"IFITM3\" and how it affects the immune system and its relation to AD is presented. GS is one of the most studied proteins with many developed candidates as inhibitors (GSI) and modulators (GSM). Examples of GSI are Semagacestat and Avagacestat while GSM includes E2012; which inhibits the cleavage activity of GS. In this report, each of the four subunits of GS is described in detail, along with the interactions between GS and its inhibitors or modulators. In addition, the FDA-approved drugs are enlisted.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"109-127"},"PeriodicalIF":3.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41194376","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 Natural Products as Antiparasitic Agents for Neglected Tropical Diseases.","authors":"Dayanna Orosco, Arturo René Mendoza, Carlos Mario Meléndez","doi":"10.2174/0115680266256963230921061925","DOIUrl":"10.2174/0115680266256963230921061925","url":null,"abstract":"<p><p>Recent developments in the use of natural product-based molecules as antiparasitic agents for Malaria, leishmaniasis (LE), Chagas disease (CD), and Human African trypanosomiasis (HAT) are reviewed. The role of diverse plants in developing bioactive species is discussed in addition to analyzing the structural diversity of natural products as active agents and the diverse biological applications in CD, HAT, LE, and Malaria. This review focuses on medicinal chemistry, emphasizing the structural characteristics of natural molecules as bioactive agents against parasitic infections caused by <i>Leishmania, Trypanosoma</i>, and <i>Plasmodium parasites</i>.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"89-108"},"PeriodicalIF":3.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41233180","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":"Use of Immunoglobulin Y Antibodies: Biosensor-based Diagnostic Systems and Prophylactic and Therapeutic Drug Delivery Systems for Viral Respiratory Diseases.","authors":"Yasemin Budama-Kilinc, Ozan Baris Kurtur, Bahar Gok, Nisanur Cakmakci, Serda Kecel-Gunduz, Necdet Mehmet Unel, Taylan Kurtulus Ozturk","doi":"10.2174/0115680266289898240322073258","DOIUrl":"10.2174/0115680266289898240322073258","url":null,"abstract":"<p><p>Respiratory viruses have caused many pandemics from past to present and are among the top global public health problems due to their rate of spread. The recently experienced COVID-19 pandemic has led to an understanding of the importance of rapid diagnostic tests to prevent epidemics and the difficulties of developing new vaccines. On the other hand, the emergence of resistance to existing antiviral drugs during the treatment process poses a major problem for society and global health systems. Therefore, there is a need for new approaches for the diagnosis, prophylaxis, and treatment of existing or new types of respiratory viruses. Immunoglobulin Y antibodies (IgYs) obtained from the yolk of poultry eggs have significant advantages, such as high production volumes, low production costs, and high selectivity, which enable the development of innovative and strategic products. Especially in diagnosing respiratory viruses, antibody-based biosensors in which these antibodies are integrated have the potential to provide superiority in making rapid and accurate diagnosis as a practical diagnostic tool. This review article aims to provide information on using IgY antibodies in diagnostic, prophylactic, and therapeutic applications for respiratory viruses and to provide a perspective for future innovative applications.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"973-985"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335116","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":"Stimuli-sensitive Chitosan-based Nanosystems-immobilized Nucleic Acids for Gene Therapy in Breast Cancer and Hepatocellular Carcinoma.","authors":"Seyed Morteza Naghib, Bahar Ahmadi, M R Mozafari","doi":"10.2174/0115680266293173240506054439","DOIUrl":"10.2174/0115680266293173240506054439","url":null,"abstract":"<p><p>Chitosan-based nanoparticles have emerged as a promising tool in the realm of cancer therapy, particularly for gene delivery. With cancer being a prevalent and devastating disease, finding effective treatment options is of utmost importance. These nanoparticles provide a unique solution by encapsulating specific genes and delivering them directly to cancer cells, offering immense potential for targeted therapy. The biocompatibility and biodegradability of chitosan, a naturally derived polymer, make it an ideal candidate for this purpose. The nanoparticles protect the genetic material during transportation and enhance its cellular uptake, ensuring effective delivery to the site of action. Furthermore, the unique properties of chitosan-based nanoparticles allow for the controlled release of genes, maximizing their therapeutic effect while minimizing adverse effects. By advancing the field of gene therapy through the use of chitosan-based nanoparticles, scientists are making significant strides toward more humane and personalized treatments for cancer patients.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"1464-1489"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944491","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":"Evaluation of Thiazolidine Derivatives with Potential Anti-ZIKV Activity.","authors":"Sayonara Maria Calado Gonçalves, Lília Vieira Galdino, Morganna Costa Lima, José Arion da Silva Moura, Douglas Carvalho Francisco Viana, Michelle Melgarejo da Rosa, Luiz Felipe Gomes Rebello Ferreira, Marcelo Zaldini Hernandes, Michelly Cristiny Pereira, Moacyr Jesus Barreto de Melo Rêgo, Ivan da Rocha Pitta, Rafael de Oliveira França, Marina Galdino da Rocha Pitta, Maira Galdino da Rocha Pitta","doi":"10.2174/0115680266315388240801053401","DOIUrl":"10.2174/0115680266315388240801053401","url":null,"abstract":"<p><strong>Objective: </strong>In this study, we have synthesized 19 Thiazolidine (TZD) derivatives to investigate their potential anti-ZIKV effects.</p><p><strong>Methods: </strong>Nineteen thiazolidine derivatives were synthesized and evaluated for their cytotoxicity and antiviral activity against the ZIKA virus.</p><p><strong>Results: </strong>Among them, six demonstrated remarkable selectivity against the ZIKV virus, exhibiting IC50 values of <5μM, and the other compounds did not demonstrate selectivity for the virus. Interestingly, several derivatives effectively suppressed the replication of ZIKV RNA copies, with derivatives significantly reducing ZIKV mRNA levels at 24 hours post-infection (hpi). Notably, two derivatives (ZKC-4 and -9) stood out by demonstrating a protective effect against ZIKV cell entry. Informed by computational analysis of binding affinity and intermolecular interactions within the NS5 domain's N-7 and O'2 positions, ZKC-4 and FT-39 displayed the highest predicted affinities. Intriguingly, ZKC-4 and ZKC-9 derivatives exhibited the most favorable predicted binding affinities for the ZIKV-E binding site.</p><p><strong>Conclusion: </strong>The significance of TZDs as potent antiviral agents is underscored by these findings, suggesting that exploring TZD derivatives holds promise for advancing antiviral therapeutic strategies.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"2224-2237"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970849","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 Molecular Targets and their Ligands for the Treatment of Alzheimer Disease.","authors":"Gülşah Bayraktar, Vildan Alptüzün","doi":"10.2174/0115680266318722240809050235","DOIUrl":"10.2174/0115680266318722240809050235","url":null,"abstract":"<p><p>Alzheimer's disease is a multifaceted neurodegenerative disease. Cholinergic dysfunction, amyloid β toxicity, tauopathies, oxidative stress, neuroinflammation are among the main pathologies of the disease. Ligands targeting more than one pathology, multi-target directed ligands, attract attention in the recent years to tackle Alzheimer's disease. In this review, we aimed to cover different biochemical pathways, that are revealed in recent years for the pathology of the disease, as druggable targets such as cannabinoid receptors, matrix metalloproteinases, histone deacetylase and various kinases including, glycogen synthase kinase-3, mitogen-activated protein kinase and c-Jun N-terminal kinase, and their ligands for the treatment of Alzheimer's disease in the hope of providing more realistic insights into the field.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"2447-2464"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016680","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}