Medicinal Chemistry Research最新文献_第7页

Advances in anticancer applications of platinum(II) complexes of dithiocarbamates 二硫代氨基甲酸铂(II)配合物在抗癌方面的应用进展

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-06-15 DOI: 10.1007/s00044-024-03257-5

Saeed Ahmad

{"title":"Advances in anticancer applications of platinum(II) complexes of dithiocarbamates","authors":"Saeed Ahmad","doi":"10.1007/s00044-024-03257-5","DOIUrl":"10.1007/s00044-024-03257-5","url":null,"abstract":"<div><p>This review presents an overview of the antitumor properties of various platinum(II) complexes of dithiocarbamates. It has been noticed that in several cases the activity is greater than cisplatin, while their toxicity level is low. The monofunctional platinum(II)-dithiocarbamate complexes comprising a labile chloride ligand possess the most effective cytotoxic behavior among the complexes discussed here. The bis(dithiocarbamato) complexes on the other hand show poor anti-proliferative potential. The complexes manifest their antitumor activity through DNA interaction that takes place <i>via</i> covalent bonding, intercalation or electrostatic interaction. The study of apoptotic activity in some cases suggests that these complexes trigger apoptosis, which causes the cell death. The induction of apoptosis is correlated with the generation of reactive oxygen species, the cell cycle arrest and the inhibition of NF-kB activity. The protective effects of dithiocarbamates against the platinum-induced toxicity have been explained. Dithiocarbamates were found to control the side effects of cisplatin and the anticancer activity of cisplatin was significantly improved in the presence of a dithiocarbamate. The study highlights that platinum(II) complexes of dithiocarbamates may be regarded as promising anticancer agents because of their effective cytotoxic properties and their potential to overcome cisplatin resistance.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 7","pages":"1133 - 1153"},"PeriodicalIF":2.6,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141336608","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}

引用次数: 0

Revolutionizing drug discovery: an AI-powered transformation of molecular docking 彻底改变药物发现：分子对接的人工智能变革

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-06-14 DOI: 10.1007/s00044-024-03253-9

Adeola Abraham Fadahunsi, Henrietta Onyinye Uzoeto, N. O. Okoro, Samuel Cosmas, Olanrewaju Ayodeji Durojaye, A. Odiba

引用次数: 0

Pharmacological assessment of disulfide–triazine hybrids: synthesis, enzyme inhibition, and molecular docking study 二硫化物-三嗪混合物的药理评估：合成、酶抑制和分子对接研究

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-06-14 DOI: 10.1007/s00044-024-03251-x

Fikret Türkan, Adnan Cetin, Przemysław Rozbicki, Ercan Oğuz, Ewa Wolińska, Danuta Branowska

{"title":"Pharmacological assessment of disulfide–triazine hybrids: synthesis, enzyme inhibition, and molecular docking study","authors":"Fikret Türkan, Adnan Cetin, Przemysław Rozbicki, Ercan Oğuz, Ewa Wolińska, Danuta Branowska","doi":"10.1007/s00044-024-03251-x","DOIUrl":"10.1007/s00044-024-03251-x","url":null,"abstract":"<div><p>Acetylcholinesterase (AChE) is indispensable for neurotransmission, while glutathione S-transferase (GST) plays a crucial role in cellular detoxification and protection. These enzymes are pivotal subjects in scientific investigations aimed at understanding neurological functions and maintaining cellular equilibrium. In pursuit of this objective, a set of disulfide–triazine hybrids (<b>1</b>, <b>2</b>, and <b>3a</b>–<b>h</b>) was effectively synthesized and methodically examined for their capacity to inhibit both AChE and GST (the Ki values for AChE range from 0.893 ± 0.117 μM to 7.961 ± 0.421 μM, while the IC<sub>50</sub> values fall within the range of 1.919–6.243 μM. For GST, the Ki values span from 2.093 ± 0.276 μM to 8.840 ± 1.934 μM, with IC<sub>50</sub> values ranging from 2.152 to 4.747 μM). After synthesizing the compounds and studying their biological effects, molecular docking analyses were conducted to understand how these compounds interact with target enzymes. This helped identify how the compounds bind and which amino acid residues are crucial for inhibition. The positive results highlight the potential of disulfide–triazine hybrids as strong inhibitors of AChE and GST, suggesting they could be further developed and optimized as therapeutic agents.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 7","pages":"1205 - 1217"},"PeriodicalIF":2.6,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141341678","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}

引用次数: 0

Development of novel fluoro-substituted rivastigmine derivatives as selective AChE inhibitors for the treatment of AD 开发新型氟取代利巴斯的明衍生物，作为治疗注意力缺失症的选择性 AChE 抑制剂

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-06-14 DOI: 10.1007/s00044-024-03250-y

Zhengwei Liu, Xinjuan Li, Mengqi Huang, Zhenhui Su, Qiyao Zhang, Yuting Li, Yi Zhou, Lintao Yu, Wenmin Liu, Zhipei Sang

{"title":"Development of novel fluoro-substituted rivastigmine derivatives as selective AChE inhibitors for the treatment of AD","authors":"Zhengwei Liu, Xinjuan Li, Mengqi Huang, Zhenhui Su, Qiyao Zhang, Yuting Li, Yi Zhou, Lintao Yu, Wenmin Liu, Zhipei Sang","doi":"10.1007/s00044-024-03250-y","DOIUrl":"10.1007/s00044-024-03250-y","url":null,"abstract":"<div><p>The classic cholinergic hypothesis was considered as the successful hypothesis due to the marketed drugs (donepezil, rivastigmine, and galantamine). The development of selective AChE inhibitor still was a promising strategy for the treatment of Alzheimer’s disease (AD). Herein, 29 novel rivastigmine derivatives was rationally developed as selective AChE inhibitors for treating AD. The target compounds were designed and evaluated through AChE/BuChE inhibition, reversibility study, and neuroprotective effect. The results in vitro showed that compound <b>9a</b> showed the best <i>ee</i>AChE inhibitory potency (IC<sub>50</sub> = 1.78 μM) and weak BuChE inhibitory potency, suggesting that compound <b>9a</b> was a selective AChE inhibitor. The molecular docking offered possible mechanism for its high AChE inhibitory potency. The further study indicated that compound <b>9a</b> was a pseudo-irreversible <i>ee</i>AChE inhibitor. Furthermore, <b>9a</b> demonstrated significant neuroprotective effect on L-Glu-induced HT22 cells injury. Further, <b>9a</b> presented favorable predicted drug-like property. Therefore, <b>9a</b> was a promising selective AChE inhibitor for treating AD.</p></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 7","pages":"1195 - 1204"},"PeriodicalIF":2.6,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141343877","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}

引用次数: 0

Unlocking therapeutic potential: exploring indole scaffolds and their structural insights as pharmacophores in designing anti-breast cancer agents 发掘治疗潜力：探索吲哚支架及其结构见解，将其作为设计抗乳腺癌药剂的药剂库

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-06-12 DOI: 10.1007/s00044-024-03241-z

Adithya Vinod, H. M. Chandra Mouli, Anupam Jana, Ramalingam Peraman

{"title":"Unlocking therapeutic potential: exploring indole scaffolds and their structural insights as pharmacophores in designing anti-breast cancer agents","authors":"Adithya Vinod, H. M. Chandra Mouli, Anupam Jana, Ramalingam Peraman","doi":"10.1007/s00044-024-03241-z","DOIUrl":"10.1007/s00044-024-03241-z","url":null,"abstract":"<div><p>Indole scaffolds are well-documented for their biological accessibility and broader therapeutic applications. The cellular interaction of the indole moiety and its intrinsic effects on cell transduction and proliferation mechanisms in cancer biology have been widely acknowledged. Despite available reports on anticancer indoles, the structural insights of indole compounds in targeting drug-resistant breast cancer have yet to be elaborated upon. Breast cancer is emerging as the most common cancer in women worldwide, affecting more than two million women annually. Considering the optimistic evidence found in recent studies on the druggability of indole derivatives for breast cancer, this review presents indole compounds of interest with anti-breast cancer activity, along with their structural insights and mechanisms. This review updates several interesting facts related to the indole interacting pathway suitable for drug-resistant breast cancer. Furthermore, the clinical pharmacokinetic and toxicity reports of these compounds are very impressive. This integrative view of indole compounds will undoubtedly pave the way for further exploratory research in the discovery of newer indole-based chemotherapeutics as efficacious leads for breast cancer.</p></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 7","pages":"1100 - 1132"},"PeriodicalIF":2.6,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141351414","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}

引用次数: 0

Current trends and future directions for the synthesis and pharmacological applications of 2-(2-cyanopyrrolidin-1-yl)-N-3-hydroxyadamantan-1-yl) acetamide (Gliptins) 2-(2-氰基吡咯烷-1-基)-N-3-羟基金刚烷-1-基)乙酰胺（格列吡嗪）的合成和药理应用的当前趋势和未来方向

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-06-11 DOI: 10.1007/s00044-024-03218-y

Shaikh Yahya, Mohammad Usman Shaikh, Prathmesh Pramod Deshpande, Sangshetti Jaiprakash Navnath, Akram Choudhary, Nisha Sharma, Mohd Shafeeque, M. Shahar Yar

{"title":"Current trends and future directions for the synthesis and pharmacological applications of 2-(2-cyanopyrrolidin-1-yl)-N-3-hydroxyadamantan-1-yl) acetamide (Gliptins)","authors":"Shaikh Yahya, Mohammad Usman Shaikh, Prathmesh Pramod Deshpande, Sangshetti Jaiprakash Navnath, Akram Choudhary, Nisha Sharma, Mohd Shafeeque, M. Shahar Yar","doi":"10.1007/s00044-024-03218-y","DOIUrl":"10.1007/s00044-024-03218-y","url":null,"abstract":"<div><p>Dipeptidyl peptidase 4 (DPP-4), well known as the T-cell antigen CD26 enzyme which, was discovered in the year of 1966 by Hopsu-Havu and Glenner. The enzyme gained considerable attention due to its vital functions, such as (1) deactivation of the incretin hormone, which is responsible for insulin catabolism, (2) hydrolyzes of opioid peptides engaged in pain modulation, etc. Moreover, DPP-4 also acts as a carrier protein and ligand for a variety of extracellular and intracellular substrates. The Finding of DPP-4 inhibitors is the newer approach to treating numerous disorders/ diseases, for example, coronary heart disease, heart failure, stroke, and Diabetes mellitus (DM). The outcomes of studies carried out in the past few decades revealed that Gliptins (DPP-4 inhibitors) is a more promising candidate than conventional hypoglycaemic agents, as the former can be taken in monotherapy once a week or conjointly with another hypoglycaemic agent. By considering all favorable properties of DPP-4 inhibitors, this excerpt was written with the primary focused on the clinically approved, orally acting Gliptin class of drugs, with an emphasizing on their conventional, modern as well as patented methods of intermediates and final product development.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 7","pages":"1031 - 1054"},"PeriodicalIF":2.6,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141356765","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}

引用次数: 0

Glutathione transporter as a target for brain drug delivery 谷胱甘肽转运体作为脑部给药的靶点

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-06-10 DOI: 10.1007/s00044-024-03225-z

Xiangming Guan

引用次数: 0

Position switch of phenylthiazoles: novel compounds with promising anti-MRSA USA300 苯基噻唑的位置转换：具有抗 MRSA 前景的新型化合物 USA300

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-06-10 DOI: 10.1007/s00044-024-03243-x

Abdelrahman A. Abuelkhir, Mariam Omara, Yosra I. Nagy, Ahmed E. Gouda, Ahmed S. Attia, Abdelrahman S. Mayhoub, Mohamed Hagras

引用次数: 0

Discovering cholinesterase inhibitors from Chinese herbal medicine with deep learning models 利用深度学习模型从中药中发现胆碱酯酶抑制剂

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-06-08 DOI: 10.1007/s00044-024-03238-8

Fulu Pan, Yang Liu, Zhiqiang Luo, Guopeng Wang, Xueyan Li, Huining Liu, Shuang Yu, Dongying Qi, Xinyu Wang, Xiaoyu Chai, Qianqian Wang, Renfang Yin, Yanli Pan

{"title":"Discovering cholinesterase inhibitors from Chinese herbal medicine with deep learning models","authors":"Fulu Pan, Yang Liu, Zhiqiang Luo, Guopeng Wang, Xueyan Li, Huining Liu, Shuang Yu, Dongying Qi, Xinyu Wang, Xiaoyu Chai, Qianqian Wang, Renfang Yin, Yanli Pan","doi":"10.1007/s00044-024-03238-8","DOIUrl":"10.1007/s00044-024-03238-8","url":null,"abstract":"<div><p>Traditional Chinese medicine (TCM) holds distinctive advantages in the management of Alzheimer’s disease. Nonetheless, a considerable gap remains in our understanding of its pharmacologically active constituents. In this study, we harnessed the potential of deep learning models to swiftly and precisely predict drug-target interactions. We conducted a systematic screening of cholinesterase (ChE) inhibitors from an extensive array of TCM ingredients, followed by rigorous validation through in vitro experiments. We constructed both a drug-target interactions (DTI) model and a blood-brain barrier permeability (BBBP) model, with both models achieving an AUPRC score exceeding 0.9. Subsequently, we conducted a screening process that identified six compounds for in vitro ChE inhibitory assay. Notably, all six compounds exhibited a robust inhibitory effect on acetylcholinesterase (AChE), while four of the six compounds demonstrated potent inhibitory activity against butyrylcholinesterase (BChE). Our findings underscore the promise of leveraging deep learning to discover inhibitors from TCM.</p></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 7","pages":"1154 - 1166"},"PeriodicalIF":2.6,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141368279","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}

引用次数: 0

New sirtuin modulators: their uncovering, pharmacophore, and implications in drug discovery 新的 sirtuin 调节剂：它们的发现、药理作用和对药物发现的影响

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-06-08 DOI: 10.1007/s00044-024-03249-5

Pei-Ti Chen, Keng Yoon Yeong

{"title":"New sirtuin modulators: their uncovering, pharmacophore, and implications in drug discovery","authors":"Pei-Ti Chen, Keng Yoon Yeong","doi":"10.1007/s00044-024-03249-5","DOIUrl":"10.1007/s00044-024-03249-5","url":null,"abstract":"<div><p>Sirtuins are a group of enzymes known as class III histone deacetylases that catalyze the deacetylation reaction and are presented across various species. In humans, they exhibit seven isoforms known as SIRT1–7, localize in distinctive cellular compartments, the nucleus (SIRT1, 6, 7), cytoplasm (SIRT2), and mitochondria (SIRT3, 4, 5). They play crucial roles in metabolism, DNA repair, and rRNA transcription. As research on sirtuins has expanded, there has been increased interest in identifying sirtuin modulators that may hold therapeutic implications in various diseases. Despite the identification of numerous sirtuin modulators, only few have entered clinical trials due to selectivity and safety concerns. Hence, subsequent research is needed to understand their mechanisms and ensure their safety profiles. This review summarizes experimental data and the status of sirtuin modulators reported from 2013 to current, aiming to contribute to the advancement of sirtuin modulation research and the identification of promising candidates for future development.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 7","pages":"1064 - 1078"},"PeriodicalIF":2.6,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-024-03249-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141369339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0