Pub Date : 2024-01-01DOI: 10.2174/0115680266318722240809050235
Gülşah Bayraktar, Vildan Alptüzün
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.
阿尔茨海默病是一种多发性神经退行性疾病。胆碱能功能障碍、淀粉样蛋白 β毒性、陶氏病、氧化应激、神经炎症是该病的主要病理变化。近年来,针对一种以上病理机制的配体,即多靶点定向配体,在应对阿尔茨海默病方面备受关注。在这篇综述中,我们旨在介绍近年来揭示的可作为药物靶点的不同生化途径,如大麻素受体、基质金属蛋白酶、组蛋白去乙酰化酶和各种激酶(包括糖原合酶激酶-3、丝裂原活化蛋白激酶和 c-Jun N 端激酶),以及它们用于治疗阿尔茨海默病的配体,希望为这一领域提供更现实的见解。
{"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}
Background: DNA methyltransferases (DNMTs) have been reported to be potential drug targets in various cancers. The major hurdle in inhibiting DNMTs is the lack of knowledge about different DNMTs and their role in the hypermethylation of gene promoters in cancer cells. Lack of information on specificity, stability, and higher toxicity of previously reported DNMT inhibitors is the major reason for inadequate epigenetic cancer therapy. DNMT1 and DNMT3A are the two DNMTs that are majorly overexpressed in cancers.
Objective: In this study, we have presented computational and experimental analyses of the potential of some natural compounds, withaferin A (Wi-A), withanone (Wi-N), and caffeic acid phenethyl ester (CAPE), as DNMT inhibitors, in comparison to sinefungin (SFG), a known dual inhibitor of DNMT1 and DNMT3A.
Methods: We used classical simulation methods, such as molecular docking and molecular dynamics simulations, to investigate the binding potential and properties of the test compounds with DNMT1 and DNMT3A. Cell culture-based assays were used to investigate the inactivation of DNMTs and the resulting hypomethylation of the p16INK4A promoter, a key tumour suppressor that is inactivated by hypermethylation in cancer cells, resulting in upregulation of its expression.
Results: Among the three test compounds (Wi-A, Wi-N, and CAPE), Wi-A showed the highest binding affinity to both DNMT1 and DNMT3A; CAPE showed the highest affinity to DNMT3A, and Wi-N showed a moderate affinity interaction with both. The binding energies of Wi-A and CAPE were further compared with SFG. Expression analysis of DNMTs showed no difference between control and treated cells. Cell viability and p16INK4A expression analysis showed a dose-dependent decrease in viability, an increase in p16INK4A, and a stronger effect of Wi-A compared to Wi-N and CAPE.
Conclusion: The study demonstrated the differential binding ability of Wi-A, Wi-N, and CAPE to DNMT1 and DNMT3A, which was associated with their inactivation, leading to hypomethylation and desilencing of the p16INK4A tumour suppressor in cancer cells. The test compounds, particularly Wi-A, have the potential for cancer therapy.
{"title":"Effect of Withaferin-A, Withanone, and Caffeic Acid Phenethyl Ester on DNA Methyltransferases: Potential in Epigenetic Cancer Therapy.","authors":"Vipul Kumar, Jaspreet Kaur Dhanjal, Anissa Nofita Sari, Mallika Khurana, Sunil C Kaul, Renu Wadhwa, Durai Sundar","doi":"10.2174/1568026623666230726105017","DOIUrl":"10.2174/1568026623666230726105017","url":null,"abstract":"<p><strong>Background: </strong>DNA methyltransferases (DNMTs) have been reported to be potential drug targets in various cancers. The major hurdle in inhibiting DNMTs is the lack of knowledge about different DNMTs and their role in the hypermethylation of gene promoters in cancer cells. Lack of information on specificity, stability, and higher toxicity of previously reported DNMT inhibitors is the major reason for inadequate epigenetic cancer therapy. DNMT1 and DNMT3A are the two DNMTs that are majorly overexpressed in cancers.</p><p><strong>Objective: </strong>In this study, we have presented computational and experimental analyses of the potential of some natural compounds, withaferin A (Wi-A), withanone (Wi-N), and caffeic acid phenethyl ester (CAPE), as DNMT inhibitors, in comparison to sinefungin (SFG), a known dual inhibitor of DNMT1 and DNMT3A.</p><p><strong>Methods: </strong>We used classical simulation methods, such as molecular docking and molecular dynamics simulations, to investigate the binding potential and properties of the test compounds with DNMT1 and DNMT3A. Cell culture-based assays were used to investigate the inactivation of DNMTs and the resulting hypomethylation of the p16<sup>INK4A</sup> promoter, a key tumour suppressor that is inactivated by hypermethylation in cancer cells, resulting in upregulation of its expression.</p><p><strong>Results: </strong>Among the three test compounds (Wi-A, Wi-N, and CAPE), Wi-A showed the highest binding affinity to both DNMT1 and DNMT3A; CAPE showed the highest affinity to DNMT3A, and Wi-N showed a moderate affinity interaction with both. The binding energies of Wi-A and CAPE were further compared with SFG. Expression analysis of DNMTs showed no difference between control and treated cells. Cell viability and p16<sup>INK4A</sup> expression analysis showed a dose-dependent decrease in viability, an increase in p16<sup>INK4A</sup>, and a stronger effect of Wi-A compared to Wi-N and CAPE.</p><p><strong>Conclusion: </strong>The study demonstrated the differential binding ability of Wi-A, Wi-N, and CAPE to DNMT1 and DNMT3A, which was associated with their inactivation, leading to hypomethylation and desilencing of the p16<sup>INK4A</sup> tumour suppressor in cancer cells. The test compounds, particularly Wi-A, have the potential for cancer therapy.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"379-391"},"PeriodicalIF":3.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9879248","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}
Cancer involves the uncontrolled, abnormal growth of cells and affects other tissues. Kinase has an impact on proliferating the cells and causing cancer. For the purpose of treating cancer, PIM kinase is a potential target. The pro-viral Integration site for moloney murine leukaemia virus (PIM) kinases is responsible for the tumorigenesis, by phosphorylating the proteins that control the cell cycle and cell proliferation. PIM-1, PIM-2, and PIM-3 are the three distinct isoforms of PIM kinases. The JAK/STAT pathway is essential for controlling how PIM genes are expressed. PIM kinase is also linked withPI3K/AKT/mTOR pathway in various types of cancers. The overexpression of PIM kinase will cause cancer. Currently, there are significant efforts being made in medication design and development to target its inhibition. A few small chemical inhibitors (E.g., SGI-1776, AZD1208, LGH447) that specifically target the PIM proteins' adenosine triphosphate (ATP)-binding domain have been identified. PIM kinase antagonists have a remarkable effect on different types of cancer. Despite conducting clinical trials on SGI-1776, the first PIM inhibitory agent, was prematurely withdrawn, making it unable to generate concept evidence. On the other hand, in recent years, it has aided in hastening the identification of multiple new PIM inhibitors. Cyanopyridines and Pyrazolo[1,5-a]pyrimidinecan act as potent PIM kinase inhibitors for cancer therapy. We explore the involvement of oncogenic transcription factor c-Mycandmi-RNA in relation to PIM kinase. In this article, we highlight the oncogenic effects, and structural insights into PIM kinase inhibitors for the treatment of cancer.
{"title":"PIM Kinase Inhibitors as Novel Promising Therapeutic Scaffolds in Cancer Therapy.","authors":"Dipanjan Karati, Ankur Saha, Souvik Roy, Swarupananda Mukherjee","doi":"10.2174/0115680266321659240906114742","DOIUrl":"10.2174/0115680266321659240906114742","url":null,"abstract":"<p><p>Cancer involves the uncontrolled, abnormal growth of cells and affects other tissues. Kinase has an impact on proliferating the cells and causing cancer. For the purpose of treating cancer, PIM kinase is a potential target. The pro-viral Integration site for moloney murine leukaemia virus (PIM) kinases is responsible for the tumorigenesis, by phosphorylating the proteins that control the cell cycle and cell proliferation. PIM-1, PIM-2, and PIM-3 are the three distinct isoforms of PIM kinases. The JAK/STAT pathway is essential for controlling how PIM genes are expressed. PIM kinase is also linked withPI3K/AKT/mTOR pathway in various types of cancers. The overexpression of PIM kinase will cause cancer. Currently, there are significant efforts being made in medication design and development to target its inhibition. A few small chemical inhibitors (E.g., SGI-1776, AZD1208, LGH447) that specifically target the PIM proteins' adenosine triphosphate (ATP)-binding domain have been identified. PIM kinase antagonists have a remarkable effect on different types of cancer. Despite conducting clinical trials on SGI-1776, the first PIM inhibitory agent, was prematurely withdrawn, making it unable to generate concept evidence. On the other hand, in recent years, it has aided in hastening the identification of multiple new PIM inhibitors. Cyanopyridines and Pyrazolo[1,5-a]pyrimidinecan act as potent PIM kinase inhibitors for cancer therapy. We explore the involvement of oncogenic transcription factor c-Mycandmi-RNA in relation to PIM kinase. In this article, we highlight the oncogenic effects, and structural insights into PIM kinase inhibitors for the treatment of cancer.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"2489-2508"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281789","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}
Pub Date : 2024-01-01DOI: 10.2174/0115680266282179240124072121
Kavya Singh, Navjeet Kaur, Ashish Prabhu
Background: SARS-CoV-2, the unique coronavirus that causes COVID-19, has wreaked damage around the globe, with victims displaying a wide range of difficulties that have encouraged medical professionals to look for innovative technical solutions and therapeutic approaches. Artificial intelligence-based methods have contributed a significant part in tackling complicated issues, and some institutions have been quick to embrace and tailor these solutions in response to the COVID-19 pandemic's obstacles. Here, in this review article, we have covered a few DL techniques for COVID-19 detection and diagnosis, as well as ML techniques for COVID-19 identification, severity classification, vaccine and drug development, mortality rate prediction, contact tracing, risk assessment, and public distancing. This review illustrates the overall impact of AI/ML tools on tackling and managing the outbreak.
Purpose: The focus of this research was to undertake a thorough evaluation of the literature on the part of Artificial Intelligence (AI) as a complete and efficient solution in the battle against the COVID-19 epidemic in the domains of detection and diagnostics of disease, mortality prediction and vaccine as well as drug development.
Methods: A comprehensive exploration of PubMed, Web of Science, and Science Direct was conducted using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) regulations to find all possibly suitable papers conducted and made publicly available between December 1, 2019, and August 2023. COVID-19, along with AI-specific words, was used to create the query syntax.
Results: During the period covered by the search strategy, 961 articles were published and released online. Out of these, a total of 135 papers were chosen for additional investigation. Mortality rate prediction, early detection and diagnosis, vaccine as well as drug development, and lastly, incorporation of AI for supervising and controlling the COVID-19 pandemic were the four main topics focused entirely on AI applications used to tackle the COVID-19 crisis. Out of 135, 60 research papers focused on the detection and diagnosis of the COVID-19 pandemic. Next, 19 of the 135 studies applied a machine-learning approach for mortality rate prediction. Another 22 research publications emphasized the vaccine as well as drug development. Finally, the remaining studies were concentrated on controlling the COVID-19 pandemic by applying AI AI-based approach to it.
Conclusion: We compiled papers from the available COVID-19 literature that used AI-based methodologies to impart insights into various COVID-19 topics in this comprehensive study. Our results suggest crucial characteristics, data types, and COVID-19 tools that can aid in medical and translational research facilitation.
{"title":"Combating COVID-19 Crisis using Artificial Intelligence (AI) Based Approach: Systematic Review.","authors":"Kavya Singh, Navjeet Kaur, Ashish Prabhu","doi":"10.2174/0115680266282179240124072121","DOIUrl":"10.2174/0115680266282179240124072121","url":null,"abstract":"<p><strong>Background: </strong>SARS-CoV-2, the unique coronavirus that causes COVID-19, has wreaked damage around the globe, with victims displaying a wide range of difficulties that have encouraged medical professionals to look for innovative technical solutions and therapeutic approaches. Artificial intelligence-based methods have contributed a significant part in tackling complicated issues, and some institutions have been quick to embrace and tailor these solutions in response to the COVID-19 pandemic's obstacles. Here, in this review article, we have covered a few DL techniques for COVID-19 detection and diagnosis, as well as ML techniques for COVID-19 identification, severity classification, vaccine and drug development, mortality rate prediction, contact tracing, risk assessment, and public distancing. This review illustrates the overall impact of AI/ML tools on tackling and managing the outbreak.</p><p><strong>Purpose: </strong>The focus of this research was to undertake a thorough evaluation of the literature on the part of Artificial Intelligence (AI) as a complete and efficient solution in the battle against the COVID-19 epidemic in the domains of detection and diagnostics of disease, mortality prediction and vaccine as well as drug development.</p><p><strong>Methods: </strong>A comprehensive exploration of PubMed, Web of Science, and Science Direct was conducted using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) regulations to find all possibly suitable papers conducted and made publicly available between December 1, 2019, and August 2023. COVID-19, along with AI-specific words, was used to create the query syntax.</p><p><strong>Results: </strong>During the period covered by the search strategy, 961 articles were published and released online. Out of these, a total of 135 papers were chosen for additional investigation. Mortality rate prediction, early detection and diagnosis, vaccine as well as drug development, and lastly, incorporation of AI for supervising and controlling the COVID-19 pandemic were the four main topics focused entirely on AI applications used to tackle the COVID-19 crisis. Out of 135, 60 research papers focused on the detection and diagnosis of the COVID-19 pandemic. Next, 19 of the 135 studies applied a machine-learning approach for mortality rate prediction. Another 22 research publications emphasized the vaccine as well as drug development. Finally, the remaining studies were concentrated on controlling the COVID-19 pandemic by applying AI AI-based approach to it.</p><p><strong>Conclusion: </strong>We compiled papers from the available COVID-19 literature that used AI-based methodologies to impart insights into various COVID-19 topics in this comprehensive study. Our results suggest crucial characteristics, data types, and COVID-19 tools that can aid in medical and translational research facilitation.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"737-753"},"PeriodicalIF":3.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691468","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}
The Hedgehog (Hh) signaling pathway plays a crucial role in diverse biological processes such as cell differentiation, proliferation, senescence, tumorigenesis, malignant transformation, and drug resistance. Aberrant Hh signaling, resulting from mutations and excessive activation, can contribute to the development of various diseases during different stages of biogenesis and development. Moreover, it has been linked to unfavorable outcomes in several human cancers, including basal cell carcinoma (BCC), multiple myeloma (MM), melanoma, and breast cancer. Hence, the presence of mutations and excessive activation of the Hh pathway presents obstacles and constraints in the realm of cancer treatment. Extant research has demonstrated that small molecule inhibitors are regarded as the most effective therapeutic approaches for targeting the Hh pathway in contrast to traditional chemotherapy and radiotherapy. Consequently, this review focuses on the present repertoire of small molecule inhibitors that target various components of the Hh pathway, including Hh ligands, Ptch receptors, Smo transmembrane proteins, and Gli nuclear transcription factors. This study provides a comprehensive analysis of small molecules' structural and functional aspects in the preclinical and clinical management of cancer. Additionally, it elucidates the obstacles encountered in targeting the Hh pathway for human cancer therapy and proposes potential therapeutic approaches.
{"title":"Current Status of Hedgehog Signaling Inhibitors.","authors":"Xiaotang Wang, Tian Wang, Xiaona Song, Jiping Gao, Guoqiang Xu, Yunhui Ma, Guohua Song","doi":"10.2174/0115680266280850231221074340","DOIUrl":"10.2174/0115680266280850231221074340","url":null,"abstract":"<p><p>The Hedgehog (Hh) signaling pathway plays a crucial role in diverse biological processes such as cell differentiation, proliferation, senescence, tumorigenesis, malignant transformation, and drug resistance. Aberrant Hh signaling, resulting from mutations and excessive activation, can contribute to the development of various diseases during different stages of biogenesis and development. Moreover, it has been linked to unfavorable outcomes in several human cancers, including basal cell carcinoma (BCC), multiple myeloma (MM), melanoma, and breast cancer. Hence, the presence of mutations and excessive activation of the Hh pathway presents obstacles and constraints in the realm of cancer treatment. Extant research has demonstrated that small molecule inhibitors are regarded as the most effective therapeutic approaches for targeting the Hh pathway in contrast to traditional chemotherapy and radiotherapy. Consequently, this review focuses on the present repertoire of small molecule inhibitors that target various components of the Hh pathway, including Hh ligands, Ptch receptors, Smo transmembrane proteins, and Gli nuclear transcription factors. This study provides a comprehensive analysis of small molecules' structural and functional aspects in the preclinical and clinical management of cancer. Additionally, it elucidates the obstacles encountered in targeting the Hh pathway for human cancer therapy and proposes potential therapeutic approaches.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"243-258"},"PeriodicalIF":3.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139477530","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}
Pub Date : 2024-01-01DOI: 10.2174/0115680266287982240517050139
Xin-Bo Zhang, Peiyuan Zhao, Yunlan Wang, Ying Zhang, Xuan Lei, Xiao Song
Background: Upon the release of the selection results of "Qin Medicine," numerous Chinese herbal medicines and proprietary Chinese medicines have regained attention. Physochlainae Radix (Huashanshen), a herbal medicine named after Mount Hua, the prominent peak in the Qinling Mountains, has garnered particular interest. Despite this, the impact of Physochlainae Radix and Qin medicines as a whole remains significantly overshadowed by the renown of Mount Hua.
Methods: Search on Using "Physochlainae Radix" as the keyword; searches were conducted across China National Knowledge Infrastructure (CNKI), Wanfang Data, WIP Database, PubMed, Web of Science, and the National Library of China databases.
Results: This study presents an overview of Physochlainae Radix by reviewing its history, chemical composition, preparation methods, planting and cultivation practices, concoctions, alkaloid detection, contraindications for use, resource recycling, and predicting quality markers.
Conclusion: To facilitate the further application and development of Physochlainae Radix, this study also addresses the challenges in the development of Qin medicines and proposes potential solutions.
{"title":"<i>Physochlainae Radix</i>: A Review of Ethnobotany, Phytochemistry, Pharmacology, Q-marker Prediction, and Future Directions.","authors":"Xin-Bo Zhang, Peiyuan Zhao, Yunlan Wang, Ying Zhang, Xuan Lei, Xiao Song","doi":"10.2174/0115680266287982240517050139","DOIUrl":"10.2174/0115680266287982240517050139","url":null,"abstract":"<p><strong>Background: </strong>Upon the release of the selection results of \"Qin Medicine,\" numerous Chinese herbal medicines and proprietary Chinese medicines have regained attention. <i>Physochlainae Radix</i> (Huashanshen), a herbal medicine named after Mount Hua, the prominent peak in the Qinling Mountains, has garnered particular interest. Despite this, the impact of <i>Physochlainae Radix</i> and <i>Qin</i> medicines as a whole remains significantly overshadowed by the renown of Mount Hua.</p><p><strong>Methods: </strong>Search on Using \"<i>Physochlainae Radix</i>\" as the keyword; searches were conducted across China National Knowledge Infrastructure (CNKI), Wanfang Data, WIP Database, PubMed, Web of Science, and the National Library of China databases.</p><p><strong>Results: </strong>This study presents an overview of <i>Physochlainae Radix</i> by reviewing its history, chemical composition, preparation methods, planting and cultivation practices, concoctions, alkaloid detection, contraindications for use, resource recycling, and predicting quality markers.</p><p><strong>Conclusion: </strong>To facilitate the further application and development of <i>Physochlainae Radix</i>, this study also addresses the challenges in the development of Qin medicines and proposes potential solutions.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"1856-1869"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455788","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}
Pub Date : 2024-01-01DOI: 10.2174/0115680266317770240718080512
Nitesh Kumar, Raj Kaushal, Pamita Awasthi
After the discovery of cis-platin, the first metal-based anticancer drugs, budotitane, and titanocene dichloride entered clinical trials. These two classes of complexes were effective against those cell lines that are resistant to cis-platin and other platinum-based drugs. However, the main limitation of these complexes is their low hydrolytic stability. After these two classes, a third generation titanium based complex, i.e. diaminebis(phenolato)bis(alkoxo) titanium(IV), was invented, which showed more hydrolytic stability and high cytotoxicity than budotitane and titanocene dichloride. The Hydrolytic stability of complexes plays an important role in cytotoxicity. Earlier research showed that hydrolytically less stable complexes decompose rapidly into non-bioavailable moiety and become inactive. The mechanism of Ti(IV) complexes of diaminebis(phenolato) bis(alkoxo) is under investigation and is presumed to involve Endoplasmic Reticulum (ER) stress, which leads to apoptosis. The proposed mechanism involves the removal of ligands from the titanium complex and the binding of the Ti center to transferrin protein and its release inside the cell. Also, the structure of the ligand plays a key role in the cytotoxicity of complexes; as the bulkiness of the ligand increased, the cytotoxic nature of complexes decreased.
{"title":"A Comprehensive Review on the Development of Titanium Complexes as Cytotoxic Agents.","authors":"Nitesh Kumar, Raj Kaushal, Pamita Awasthi","doi":"10.2174/0115680266317770240718080512","DOIUrl":"10.2174/0115680266317770240718080512","url":null,"abstract":"<p><p>After the discovery of cis-platin, the first metal-based anticancer drugs, budotitane, and titanocene dichloride entered clinical trials. These two classes of complexes were effective against those cell lines that are resistant to cis-platin and other platinum-based drugs. However, the main limitation of these complexes is their low hydrolytic stability. After these two classes, a third generation titanium based complex, i.e. diaminebis(phenolato)bis(alkoxo) titanium(IV), was invented, which showed more hydrolytic stability and high cytotoxicity than budotitane and titanocene dichloride. The Hydrolytic stability of complexes plays an important role in cytotoxicity. Earlier research showed that hydrolytically less stable complexes decompose rapidly into non-bioavailable moiety and become inactive. The mechanism of Ti(IV) complexes of diaminebis(phenolato) bis(alkoxo) is under investigation and is presumed to involve Endoplasmic Reticulum (ER) stress, which leads to apoptosis. The proposed mechanism involves the removal of ligands from the titanium complex and the binding of the Ti center to transferrin protein and its release inside the cell. Also, the structure of the ligand plays a key role in the cytotoxicity of complexes; as the bulkiness of the ligand increased, the cytotoxic nature of complexes decreased.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"2117-2128"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897044","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}
Pub Date : 2024-01-01DOI: 10.2174/0115680266314560240806101445
Siarhei A Dabravolski, Elizaveta M Pleshko, Vasily N Sukhorukov, Victor Y Glanz, Igor A Sobenin, Alexander N Orekhov
Mediterranean diet is frequently associated with longevity and a lower incidence of adverse cardiovascular events because of the biological activities and health effects of olives - its key component. Olive oil, olive leaf extract, fruits and different by-products contain many bioactive components that exert anti-oxidant, anti-inflammatory and anti-apoptotic activities. In this review, we focus on the recent studies exploring molecular mechanisms underlying the cardioprotective properties of different olive oils, olive leave extracts, and specific micro-constituents (such as oleuropein, tyrosol, hydroxytyrosol and others) in vitro on rodent models and in clinical trials on human subjects. Particularly, hydroxytyrosol and oleuropein were identified as the major bioactive compounds responsible for the antioxidant, anti-inflammatory, anti-platelet aggregation and anti-atherogenic activities of olive oil. In total, the discussed results demonstrated a positive association between the consumption of olive oil and improvement in outcomes in atherosclerosis, diabetes, myocardial infarction, heart failure, hypertension and obesity.
{"title":"Use of Olives-derived Phytochemicals for Prevention and Treatment of Atherosclerosis: An Update.","authors":"Siarhei A Dabravolski, Elizaveta M Pleshko, Vasily N Sukhorukov, Victor Y Glanz, Igor A Sobenin, Alexander N Orekhov","doi":"10.2174/0115680266314560240806101445","DOIUrl":"10.2174/0115680266314560240806101445","url":null,"abstract":"<p><p>Mediterranean diet is frequently associated with longevity and a lower incidence of adverse cardiovascular events because of the biological activities and health effects of olives - its key component. Olive oil, olive leaf extract, fruits and different by-products contain many bioactive components that exert anti-oxidant, anti-inflammatory and anti-apoptotic activities. In this review, we focus on the recent studies exploring molecular mechanisms underlying the cardioprotective properties of different olive oils, olive leave extracts, and specific micro-constituents (such as oleuropein, tyrosol, hydroxytyrosol and others) <i>in vitro</i> on rodent models and in clinical trials on human subjects. Particularly, hydroxytyrosol and oleuropein were identified as the major bioactive compounds responsible for the antioxidant, anti-inflammatory, anti-platelet aggregation and anti-atherogenic activities of olive oil. In total, the discussed results demonstrated a positive association between the consumption of olive oil and improvement in outcomes in atherosclerosis, diabetes, myocardial infarction, heart failure, hypertension and obesity.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"2173-2190"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003816","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}
Pub Date : 2024-01-01DOI: 10.2174/0115680266284527240118041129
Ekta Shirbhate, Vaibhav Singh, Rakesh Kore, Subham Vishwakarma, Ravichandran Veerasamy, Amit K Tiwari, Harish Rajak
Scientists are constantly researching and launching potential chemotherapeutic agents as an irreplaceable weapon to fight the battle against cancer. Despite remarkable advancement over the past several decades to wipe out cancer through early diagnosis, proper prevention, and timely treatment, cancer is not ready to give up and leave the battleground. It continuously tries to find some other way to give a tough fight for its survival, either by escaping from the effect of chemotherapeutic drugs or utilising its own chemical messengers like cytokines to ensure resistance. Cytokines play a significant role in cancer cell growth and progression, and the present article highlights their substantial contribution to mechanisms of resistance toward therapeutic drugs. Multiple clinical studies have even described the importance of specific cytokines released from cancer cells as well as stromal cells in conferring resistance. Herein, we discuss the different mechanism behind drug resistance and the crosstalk between tumor development and cytokines release and their contribution to showing resistance towards chemotherapeutics. As a part of this review, different approaches to cytokines profile have been identified and employed to successfully target new evolving mechanisms of resistance and their possible treatment options.
{"title":"The Role of Cytokines in Activation of Tumour-promoting Pathways and Emergence of Cancer Drug Resistance.","authors":"Ekta Shirbhate, Vaibhav Singh, Rakesh Kore, Subham Vishwakarma, Ravichandran Veerasamy, Amit K Tiwari, Harish Rajak","doi":"10.2174/0115680266284527240118041129","DOIUrl":"10.2174/0115680266284527240118041129","url":null,"abstract":"<p><p>Scientists are constantly researching and launching potential chemotherapeutic agents as an irreplaceable weapon to fight the battle against cancer. Despite remarkable advancement over the past several decades to wipe out cancer through early diagnosis, proper prevention, and timely treatment, cancer is not ready to give up and leave the battleground. It continuously tries to find some other way to give a tough fight for its survival, either by escaping from the effect of chemotherapeutic drugs or utilising its own chemical messengers like cytokines to ensure resistance. Cytokines play a significant role in cancer cell growth and progression, and the present article highlights their substantial contribution to mechanisms of resistance toward therapeutic drugs. Multiple clinical studies have even described the importance of specific cytokines released from cancer cells as well as stromal cells in conferring resistance. Herein, we discuss the different mechanism behind drug resistance and the crosstalk between tumor development and cytokines release and their contribution to showing resistance towards chemotherapeutics. As a part of this review, different approaches to cytokines profile have been identified and employed to successfully target new evolving mechanisms of resistance and their possible treatment options.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"523-540"},"PeriodicalIF":3.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139520433","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}
Annually, a significant number of individuals succumb to cancer, an anomalous cellular condition characterized by uncontrolled cellular proliferation and the emergence of highly perilous tumors. Identifying underlying molecular mechanism(s) driving disease progression has led to various inventive therapeutic approaches, many of which are presently under pre-clinical and/or clinical trials. Over the recent years, numerous alternative strategies for addressing cancer have also been proposed and put into practice. This article delineates the modern therapeutic drugs employed in cancer treatment and their associated toxicity. Due to inherent drug toxicity associated with most modern treatments, demand rises for alternative therapies and phytochemicals with minimal side effects and proven efficacy against cancer. Analogs of taxol, Vinca alkaloids like vincristine and vinblastine, and podophyllotoxin represent a few illustrative examples in this context. The phytochemicals often work by modifying the activity of molecular pathways that are thought to be involved in the onset and progression of cancer. The principal objective of this study is to provide an overview of our current understanding regarding the pharmacologic effects and molecular targets of the active compounds found in natural products for cancer treatment and collate information about the recent advancements in this realm. The authors' interest in advancing the field of phytochemical research stems from both the potential of these compounds for use as drugs as well as their scientific validity. Accordingly, the significance of herbal formulations is underscored, shedding light on anticancer phytochemicals that are sought after at both pre-clinical and clinical levels, with discussion on the opportunities and challenges in pre-clinical and clinical cancer studies.
{"title":"Phytotherapeutics in Cancer: From Potential Drug Candidates to Clinical Translation.","authors":"Parul Grover, Kulbhushan Thakur, Monika Bhardwaj, Lovekesh Mehta, Soom Nath Raina, Vijay Rani Rajpal","doi":"10.2174/0115680266282518231231075311","DOIUrl":"10.2174/0115680266282518231231075311","url":null,"abstract":"<p><p>Annually, a significant number of individuals succumb to cancer, an anomalous cellular condition characterized by uncontrolled cellular proliferation and the emergence of highly perilous tumors. Identifying underlying molecular mechanism(s) driving disease progression has led to various inventive therapeutic approaches, many of which are presently under pre-clinical and/or clinical trials. Over the recent years, numerous alternative strategies for addressing cancer have also been proposed and put into practice. This article delineates the modern therapeutic drugs employed in cancer treatment and their associated toxicity. Due to inherent drug toxicity associated with most modern treatments, demand rises for alternative therapies and phytochemicals with minimal side effects and proven efficacy against cancer. Analogs of taxol, <i>Vinca</i> alkaloids like vincristine and vinblastine, and podophyllotoxin represent a few illustrative examples in this context. The phytochemicals often work by modifying the activity of molecular pathways that are thought to be involved in the onset and progression of cancer. The principal objective of this study is to provide an overview of our current understanding regarding the pharmacologic effects and molecular targets of the active compounds found in natural products for cancer treatment and collate information about the recent advancements in this realm. The authors' interest in advancing the field of phytochemical research stems from both the potential of these compounds for use as drugs as well as their scientific validity. Accordingly, the significance of herbal formulations is underscored, shedding light on anticancer phytochemicals that are sought after at both pre-clinical and clinical levels, with discussion on the opportunities and challenges in pre-clinical and clinical cancer studies.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":"1050-1074"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139566587","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}