Medicinal Chemistry Research最新文献

Nanosensing doxorubicin: a new frontier in medicinal chemistry 纳米感应阿霉素：药物化学的新前沿

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-05-08 DOI: 10.1007/s00044-025-03421-5

Nazila Karzad, Samad Rastmanesh, Elham Shaterian, Hamed Shaterian, Ahmad Mobed

{"title":"Nanosensing doxorubicin: a new frontier in medicinal chemistry","authors":"Nazila Karzad, Samad Rastmanesh, Elham Shaterian, Hamed Shaterian, Ahmad Mobed","doi":"10.1007/s00044-025-03421-5","DOIUrl":"10.1007/s00044-025-03421-5","url":null,"abstract":"<div><p>The advent of nanosensing technologies marks a significant advancement in medicinal chemistry, particularly in the detection and monitoring of therapeutic agents such as doxorubicin. This review aims to elucidate the development of cutting-edge biosensor technologies specifically tailored for the sensitive and selective detection of doxorubicin, a cornerstone chemotherapeutic agent. We critically analyze various recently developed nanosensors, including electrochemical sensors and optical sensors, highlighting their distinct mechanisms, advantages, and limitations. Unlike previous literature, this review synthesizes current research findings to provide a comprehensive overview of how these innovative nanosensing platforms can enhance drug monitoring, improve therapeutic outcomes, and support personalized medicine approaches. By addressing the existing challenges in doxorubicin detection, our findings underscore the transformative potential of integrating nanotechnology with biosensing applications, ultimately contributing to more effective cancer treatment strategies.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 6","pages":"1253 - 1268"},"PeriodicalIF":2.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125749","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

Design and discovery of POLQ helicase domain inhibitors by virtual screening and machine learning 通过虚拟筛选和机器学习设计和发现POLQ解旋酶结构域抑制剂

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-05-08 DOI: 10.1007/s00044-025-03423-3

Wei Feng, Lei Liu, Lingjun Li, Peng Du, Zhichen Yuan, Jing Yuan, Changjiang Huang, Zijian Qin

{"title":"Design and discovery of POLQ helicase domain inhibitors by virtual screening and machine learning","authors":"Wei Feng, Lei Liu, Lingjun Li, Peng Du, Zhichen Yuan, Jing Yuan, Changjiang Huang, Zijian Qin","doi":"10.1007/s00044-025-03423-3","DOIUrl":"10.1007/s00044-025-03423-3","url":null,"abstract":"<div><p>DNA polymerase theta (Polθ or POLQ) is an attractive target for treating BRCA-deficient cancers. In the present work, several computational approaches were employed for the design and discovery of novel POLQ helicase domain inhibitors. A dataset was constructed by curating a total of 781 known inhibitors, which were used to develop binary classification models using random forests to distinguish between highly and weakly active inhibitors. The Matthews correlation coefficient of the consensus model reached 0.771 for the test set. A virtual screening procedure of 3.4 million molecules was conducted based on shape similarity and predictions from the consensus model to identify four hits and a favorable benzothiazole moiety. A molecular generation model was trained using molecules from both the curated dataset and the identified hits to generate potential inhibitors, which were subsequently predicted by the consensus model. Finally, eight compounds were selected and synthesized for biochemical testing, leading to the identification of compound <b>19</b>, which had a novel scaffold and acceptable potency: inhibition rates of 80.7% at a concentration of 100 nM and 39.5% at a concentration of 10 nM. Compound <b>19</b> could serve as a suitable starting point for further optimization efforts in medicinal chemistry.</p><div><figure><div><div><picture><source><img></source></picture></div><div><p>Machine Learning, Virtual Screening, Molecular Generation, Compound Synthesis, and Biochemical Testing in the Discovery of POLQ Helicase Domain Inhibitors.</p></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 6","pages":"1377 - 1391"},"PeriodicalIF":2.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125748","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

3,7-Diazabicyclo[3.3.1]nonanes and 1,3-diazaadamantanes containing monoterpenoid moieties as synthetic adaptogens: synthesis, ADMET predictions, and in vivo biological activity 含有单萜类基团的3,7-二氮杂双环壬烷和1,3-二氮杂金刚烷作为合成适应原：合成、ADMET预测和体内生物活性

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-05-05 DOI: 10.1007/s00044-025-03414-4

Anastasiia A. Kotliarova, Konstantin Yu. Ponomarev, Ekaterina A. Morozova, Evgeniy V. Suslov, Alla V. Pavlova, Tatyana G. Tolstikova, Konstantin P. Volcho, Nariman F. Salakhutdinov

{"title":"3,7-Diazabicyclo[3.3.1]nonanes and 1,3-diazaadamantanes containing monoterpenoid moieties as synthetic adaptogens: synthesis, ADMET predictions, and in vivo biological activity","authors":"Anastasiia A. Kotliarova, Konstantin Yu. Ponomarev, Ekaterina A. Morozova, Evgeniy V. Suslov, Alla V. Pavlova, Tatyana G. Tolstikova, Konstantin P. Volcho, Nariman F. Salakhutdinov","doi":"10.1007/s00044-025-03414-4","DOIUrl":"10.1007/s00044-025-03414-4","url":null,"abstract":"<div><p>Fatigue is a widespread issue that affects both mental and physical performance, yet effective treatments remain limited. This study focused on developing and evaluating new synthetic adaptogens—compounds designed to enhance endurance and reduce fatigue. We synthesized and tested derivatives of 3,7-diazabicyclo[3.3.1]nonanes (bispidine) and 1,3-diazaadamantanes, incorporating monoterpenoid fragments to improve their pharmacological properties. Using SwissADME and PreADMET tools, we predicted that most of these compounds would be well-absorbed in the gastrointestinal tract and capable of crossing the blood-brain barrier. Among them, compound <b>2</b>, a 1,3-diazaadamantane derivative, stood out for its strong antifatigue effects at 10 mg/kg in swimming and running endurance tests in in vivo experiments with mice, even outperforming the reference drug bromantane. Acute toxicity tests showed that this compound has a high safety margin, with an LD<sub>50</sub> value 237.5 times greater than its effective dose. Further analysis of structure-activity relationships revealed that monosubstituted 1,3-diazaadamantane derivatives had the most promising effects, suggesting that specific chemical modifications can enhance performance. These findings indicate that this new class of synthetic adaptogens could offer a safe and effective way to combat fatigue, making them strong candidates for further pharmacological research and potential therapeutic use.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 6","pages":"1347 - 1363"},"PeriodicalIF":2.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125576","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 caffeic acid derivatives as multifunctional agents for the treatment of AD 新型咖啡酸衍生物作为治疗AD的多功能药物的开发

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-05-05 DOI: 10.1007/s00044-025-03416-2

Kerong Hu, Jing Yang, Qiyao Zhang, Xinxin Wang, Yujie Xu, Yuxin Zhang, Zhenghuai Tan, Wenmin Liu, Rui Chen, Zhipei Sang

{"title":"Development of novel caffeic acid derivatives as multifunctional agents for the treatment of AD","authors":"Kerong Hu, Jing Yang, Qiyao Zhang, Xinxin Wang, Yujie Xu, Yuxin Zhang, Zhenghuai Tan, Wenmin Liu, Rui Chen, Zhipei Sang","doi":"10.1007/s00044-025-03416-2","DOIUrl":"10.1007/s00044-025-03416-2","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder for which the multi-target-directed ligand (MTDL) strategy offers a promising therapeutic approach. In this study, a caffeic acid-dopamine hybrid was designed and evaluated for its multifunctional activities. Subsequently, two derivatives incorporating a carbamate fragment were synthesized. Among these, compound <b>3</b> demonstrated excellent antioxidant activity, significant inhibition of self-induced A<i>β</i><sub>1–42</sub> aggregation, anti-inflammatory properties, and neuroprotective effects, though it exhibited weak cholinesterase inhibition and limited blood-brain barrier (BBB) permeability. In contrast, the derivative <b>TM-2</b> showed potent butyrylcholinesterase inhibition (IC<sub>50</sub> = 0.36 μM), potential antioxidant activity, and significant inhibition of self-induced A<i>β</i><sub>1–42</sub> aggregation (48.9%). <b>TM-2</b> also reduced NO and IL-6 levels, provided significant anti-inflammatory effects, and exhibited neuroprotective effects against Glu-/A<i>β</i><sub>25–35</sub>-induced injury in PC12 cells. Importantly, <b>TM-2</b> demonstrated BBB permeability in vitro and significantly improved memory impairment in a scopolamine-induced mouse model. These findings suggest that <b>TM-2</b> is a promising multifunctional agent for the treatment of AD.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 6","pages":"1364 - 1376"},"PeriodicalIF":2.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125575","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

Discovery of a novel selenamide derivative as potent activator of aldehyde dehydrogenase 2 for cardioprotective applications 发现一种新的selenamide衍生物，作为醛脱氢酶2的有效活化剂，用于心脏保护应用

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-05-03 DOI: 10.1007/s00044-025-03415-3

Yi Yang, Yue Yao, Junyang Huang, Zhan Shi, Xicheng Wang, Wei Li, Yishu Zhang, Jian Li, Yixiang Xu, Xiaokang Li

{"title":"Discovery of a novel selenamide derivative as potent activator of aldehyde dehydrogenase 2 for cardioprotective applications","authors":"Yi Yang, Yue Yao, Junyang Huang, Zhan Shi, Xicheng Wang, Wei Li, Yishu Zhang, Jian Li, Yixiang Xu, Xiaokang Li","doi":"10.1007/s00044-025-03415-3","DOIUrl":"10.1007/s00044-025-03415-3","url":null,"abstract":"<div><p>Aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme, plays a pivotal role in the metabolism of endogenous reactive aldehydes and functions as a crucial defense mechanism against oxidative stress. The inactive ALDH2 rs671 polymorphism has been implicated in an elevated risk of various cardiovascular diseases, such as myocardial infarction, cardiac arrhythmia, coronary heart disease, and heart failure. Alda-1 is currently the most widely recognized ALDH2 activator and its anti-heart failure properties have been extensively reported. However, Alda-1 possesses limitations in terms of pharmacokinetic properties, safety, and bioavailability, which hinder its broad clinical application. Therefore, the development of novel ALDH2 activators represents a promising novel therapeutic approach. In this study, we employed a bioisosteric substitution strategy to modify the amide bond of Alda-1. Consequently, a selenamide derivative <b>A8</b> was discovered to exhibit potent ALDH2 activation activity at the submicromolar level (ALDH2*1: EC<sub>50</sub> = 0.21 ± 0.03 μM; ALDH2*2: EC<sub>50</sub> = 0.31 ± 0.03 μM) and showed reduced cytotoxicity compared to Alda-1 in H9c2 and HepG2 cell lines. Furthermore, <b>A8</b> provided potent protection of cardiomyocytes and showed enhanced efficiency in metabolizing endogenous reactive aldehydes. Our findings present <b>A8</b> as a valuable lead compound for advancing the development of ALDH2 activators, thereby offering new avenues for cardioprotective therapies.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 6","pages":"1332 - 1346"},"PeriodicalIF":2.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125600","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

Benzoxa-[2,1,3]-diazole substituted amino acid hydrazides as therapeutics for drug-resistant Mycobacterium tuberculosis 苯并恶a-[2,1,3]-二唑取代氨基酸肼治疗耐药结核分枝杆菌

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-05-03 DOI: 10.1007/s00044-025-03417-1

Ahmed K. B. Aljohani, Yucheng Lu, Kelly J. Jackson, Paul G. Waddell, Jason H. Gill, Alistair K. Brown, Jonathan D. Sellars

{"title":"Benzoxa-[2,1,3]-diazole substituted amino acid hydrazides as therapeutics for drug-resistant Mycobacterium tuberculosis","authors":"Ahmed K. B. Aljohani, Yucheng Lu, Kelly J. Jackson, Paul G. Waddell, Jason H. Gill, Alistair K. Brown, Jonathan D. Sellars","doi":"10.1007/s00044-025-03417-1","DOIUrl":"10.1007/s00044-025-03417-1","url":null,"abstract":"<div><p>The global burden of tuberculosis is on the rise and continues to be alarmingly high, with a notable prevalence of multidrug-resistant disease. Despite a promising drug development pipeline, the levels of resistance to these therapeutics remain significant, underscoring the need for new, innovative drugs to tackle this clinical issue. Benzoxadiazoles and their derivatives have become a valuable foundation for the development of next-generation antibacterial, antifungal, and anticancer agents. Herein, we explore the benzoxa-[2,1,3]-diazole scaffold as a promising framework for antimycobacterial development. Building on prior work, thirty-two amino acid hydrazide derivatives were synthesised using a modular approach, allowing variation of both the aryl hydrazine and amino acid moieties. These analogues were evaluated for activity against wild-type, isoniazid-resistant, and multidrug-resistant mycobacterial strains using the REMA assay, with several analogues demonstrating notable inhibitory activity. Overall, the series of novel benzoxa-[2,1,3]-diazole amino acid hydrazides demonstrates that through manipulation and optimisation of the amino acid hydrazide moieties, it is feasible to engineer potent compounds with improved antimycobacterial activity against both wild-type bacteria and, crucially, drug-resistant strains of the disease.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 6","pages":"1269 - 1275"},"PeriodicalIF":2.6,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-025-03417-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125555","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

Design and synthesis of novel 1H-1,2,3-triazolecarbohydrazides and 1,2,4-triazoloazines based on them for anticancer drug discovery 基于它们的新型1h -1,2,3-三唑碳酰肼和1,2,4-三唑嗪的设计与合成，用于抗癌药物的发现

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-05-02 DOI: 10.1007/s00044-025-03419-z

Daria Zakopailo, Yevhen Blashchak, Mykola Тupychak, Nataliya Finiuk, Nazariy Pokhodylo

{"title":"Design and synthesis of novel 1H-1,2,3-triazolecarbohydrazides and 1,2,4-triazoloazines based on them for anticancer drug discovery","authors":"Daria Zakopailo, Yevhen Blashchak, Mykola Тupychak, Nataliya Finiuk, Nazariy Pokhodylo","doi":"10.1007/s00044-025-03419-z","DOIUrl":"10.1007/s00044-025-03419-z","url":null,"abstract":"<div><p>The synthesis of (1<i>H-</i>1,2,3-triazol-4-yl)-1,2,4-triazolazine derivatives was achieved via a multi-step synthesis starting from 1<i>H-</i>1,2,3-triazole-4-carboxylic acids, followed by acylation and ring closure under the influence of POCl₃. The title compounds were tested for cytotoxicity against a range of cancer cell lines, including A549 human lung carcinoma, HCT116 colon carcinoma, Jurkat T-leukemia, and KB3-1 human cervical carcinoma. The compounds demonstrated varying degrees of activity, with several showing potent cytotoxic effects, particularly against human lung carcinoma A549 and human leukemia Jurkat T-cells. The results suggest that ring closure significantly influences the bioactivity of the compounds, enhancing their cytotoxic properties. The study indicates the potential of (1<i>H-</i>1,2,3-triazol-4-yl)-1,2,4-triazolazine derivatives as promising candidates for cancer therapy, especially those with specific substituent patterns that enhance their antiproliferative effects.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 6","pages":"1321 - 1331"},"PeriodicalIF":2.6,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125546","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

Exploring putative histone deacetylase inhibitors with antiproliferative activity of chrysin derivatives 探索具有抗增殖活性的组蛋白去乙酰化酶抑制剂

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-05-01 DOI: 10.1007/s00044-025-03418-0

Thitiporn Kamloon, Thanaset Senawong, Gulsiri Senawong, Narissara Namwan, Pakit Kumboonma, La-or Somsakeesit, Puracheth Ritchumpon, Mongkol Nontakitticharoen, Pitak Nasomjai, Chanokbhorn Phaosiri

{"title":"Exploring putative histone deacetylase inhibitors with antiproliferative activity of chrysin derivatives","authors":"Thitiporn Kamloon, Thanaset Senawong, Gulsiri Senawong, Narissara Namwan, Pakit Kumboonma, La-or Somsakeesit, Puracheth Ritchumpon, Mongkol Nontakitticharoen, Pitak Nasomjai, Chanokbhorn Phaosiri","doi":"10.1007/s00044-025-03418-0","DOIUrl":"10.1007/s00044-025-03418-0","url":null,"abstract":"<div><p>Thirty-three derivatives of chrysin were designed and synthesized to evaluate biological activities. All compounds were characterized using spectroscopy techniques (IR, <sup>1</sup>H NMR and <sup>13</sup>C NMR). Moreover, twelve new derivatives were fully characterized via the HRMS technique. The derivatives and the lead compound, chrysin (<b>1</b>) were screened against HDAC inhibition at 100 µM. Three derivatives (<b>C22</b>, <b>C23</b> and <b>C24</b>) demonstrated the most effective inhibition against HDACs with the IC<sub>50</sub> values as 27.13 ± 2.74 µM to 47.47 ± 1.13 µM. Furthermore, the HDAC8 inhibitory activity of compounds <b>C22</b> and <b>C23</b> (IC<sub>50</sub> = 75.37 ± 3.42 µM and 79.74 ± 0.41 µM, respectively) were more potent than that of chrysin (<b>1</b>) (IC<sub>50</sub> > 100 µM). A molecular docking study found that the most active compound <b>C22</b> was more selective with HDAC8 (ΔG = −8.54 kcal/mol) than other isoforms (HDAC1, 2 and 3). The carboxyl moiety of the strongest derivatives plays an essential role in chelation with the Zn<sup>2+</sup> cofactor based on metal chelation assay. The Western blot assay confirmed that compounds <b>C23</b> and <b>C24</b> were the best HDACis. The most selective HDAC8 inhibitor, compound <b>C22</b>, showed the IC<sub>50</sub> value as 13.04 ± 1.08 µM against colon cancer cell lines (HCT-116), whereas compound <b>C24</b> exhibited the lowest IC<sub>50</sub> value as 11.96 ± 0.18 µM against the same cancer cell lines. The ClogP values of all derivatives were acceptable for oral administration (ClogP = 3.57 to 4.26). Therefore, the chrysin derivatives <b>C22</b>, <b>C23</b> and <b>C24</b> showed potential for further development as anti-cancer candidates.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 6","pages":"1308 - 1320"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125541","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

Pharmacological significance of palbociclib and its derivatives in cancer treatment and prevention: an update 帕博西尼及其衍生物在癌症治疗和预防中的药理意义：最新进展

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-04-25 DOI: 10.1007/s00044-025-03411-7

Shagufta, Irshad Ahmad, Laila Zeyad Bazbouz, Noora Ali Nasar, Fatme Ghassan Ibrahim, Dana Mahmoud Alkheder

{"title":"Pharmacological significance of palbociclib and its derivatives in cancer treatment and prevention: an update","authors":"Shagufta, Irshad Ahmad, Laila Zeyad Bazbouz, Noora Ali Nasar, Fatme Ghassan Ibrahim, Dana Mahmoud Alkheder","doi":"10.1007/s00044-025-03411-7","DOIUrl":"10.1007/s00044-025-03411-7","url":null,"abstract":"<div><p>Palbociclib is a selective cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor that emerged as a significant therapeutic agent in the treatment of hormone receptor-positive, HER2-negative breast cancer. This review comprehensively highlights the pharmacological significance of palbociclib and its recently developed derivatives, focusing on mechanisms of action, chemical synthesis strategies, pharmacological profile and potential benefits in cancer treatment. We explored the rationale behind structural modifications and chemical derivatization of palbociclib that have been developed to enhance its therapeutic efficacy and mitigate side effects. This review offers an update on the latest advancement in palbociclib derivatives and explores their potential to improve therapeutic efficacy with minimal side effects. The detailed analysis of recent developments and ongoing research will support the designing of more efficient CDK4/6 inhibitors and provide direction in development of future cancer treatment. We anticipate that the information provided in this review will be beneficial to readers and scientist working towards development of effective cancer treatment specifically towards next-generation CDK4/6 inhibitors with improved therapeutic and safety profiles.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 6","pages":"1237 - 1252"},"PeriodicalIF":2.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125708","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

Design, synthesis and antitumor activity study of tubulin/HDAC6 dual targeting inhibitor 微管蛋白/HDAC6双靶向抑制剂的设计、合成及抗肿瘤活性研究

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-04-24 DOI: 10.1007/s00044-025-03413-5

Congcong Zheng, Yi Zhang, Yepeng Luan

{"title":"Design, synthesis and antitumor activity study of tubulin/HDAC6 dual targeting inhibitor","authors":"Congcong Zheng, Yi Zhang, Yepeng Luan","doi":"10.1007/s00044-025-03413-5","DOIUrl":"10.1007/s00044-025-03413-5","url":null,"abstract":"<div><p>Cancer combination therapy is a novel strategy to circumvent drug resistance in highly metastatic and advanced malignancies. To this end, we designed and synthesized a series of dual-targeting compounds that target tubulin and HDAC6 simultaneously. Out of them, compound named as <b>6-4</b> possessed potent inhibitory activity against tubulin polymerization and strong antiproliferative activity to the cancer cell lines tested. <b>6-4</b> was able to inhibit tubulin polymerization and disrupt the microtubule network of tumor cells. Significant downregulation of tubulin deacetylation was also observed after the treatment of <b>6-4</b> which indicated its inhibition toward HDAC6. Mechanism studies demonstrated that <b>6-4</b> could arrest cell cycle in G2/M phase and induce apoptosis in a dose-dependent manner. In addition, <b>6-4</b> can suppress metastasis of Hela cells, and significantly inhibit the formation of HUVEC tubes. All these results suggest that <b>6-4</b> should be a promising candidate for the treatment of cancer.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 6","pages":"1293 - 1307"},"PeriodicalIF":2.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125622","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