Medicinal Chemistry Research最新文献_第10页

Glycyrrhizin and its derivatives: an emerging secondary metabolite arsenal of Glycyrrhiza glabra 甘草酸及其衍生物：一个新兴的甘草酸次级代谢物库

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-01-31 DOI: 10.1007/s00044-025-03376-7

Aadil Rasool, Tanveer Ali Dar

{"title":"Glycyrrhizin and its derivatives: an emerging secondary metabolite arsenal of Glycyrrhiza glabra","authors":"Aadil Rasool, Tanveer Ali Dar","doi":"10.1007/s00044-025-03376-7","DOIUrl":"10.1007/s00044-025-03376-7","url":null,"abstract":"<div><p>The pharmacological characteristics of secondary metabolites and their promising use in agriculture, medicine and industry has attracted immense attention from the scientific community. Glycyrrhizin, a triterpenoid saponin from <i>Glycyrrhiza glabra</i> (licorice), has also garnered substantial attention due to its diverse range of biological activities and therapeutic potential. This review provides a comprehensive overview of glycyrrhizin and its derivatives, accentuating their pharmacological activities along with their primary mechanisms of action. Glycyrrhizin exhibits notable antidiabetic, antiviral, anti-inflammatory, antifungal and anticancer activities. All these activities are attributed to its ability to modulate various cellular pathways and immune responses. Its anti-inflammatory effects are primarily facilitated through the inhibition of NF-κB and other pro-inflammatory cytokines, while its antiviral efficacy has been shown to extend to a broad spectrum of viruses, including SARS-CoV-2. Glycyrrhizin explores anticancer potential through its capacity to inhibit proliferation, induce apoptosis, and suppress metastasis. Future studies should be focussed on the development of novel derivatives and formulations, particularly nano-formulations, to enhance efficacy and safety, positioning glycyrrhizin and its derivatives as emerging arsenal candidates in the dominion of natural product-based therapeutics.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 4","pages":"745 - 763"},"PeriodicalIF":2.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622258","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, optimization and biological evaluation of chromone derivatives as novel BRD4 inhibitors 作为新型BRD4抑制剂的色素衍生物的发现、优化和生物学评价

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-01-30 DOI: 10.1007/s00044-025-03380-x

Zhao-Tong Jia, You Li, Wei Shi, Jian-Qiang Qian, Ya-Yu Xu, Hai-Ran Fan, Xiao-Long Hu, Hao Wang

{"title":"Discovery, optimization and biological evaluation of chromone derivatives as novel BRD4 inhibitors","authors":"Zhao-Tong Jia, You Li, Wei Shi, Jian-Qiang Qian, Ya-Yu Xu, Hai-Ran Fan, Xiao-Long Hu, Hao Wang","doi":"10.1007/s00044-025-03380-x","DOIUrl":"10.1007/s00044-025-03380-x","url":null,"abstract":"<div><p>Bromodomain-containing protein 4 (BRD4), as the reader of epigenetics, could regulate gene transcription by recognizing acetylated lysine of histones. In recent years, researchers have found that dysregulation of BRD4 leads to the occurrence and development of various cancers, making BRD4 a promising target for cancer therapy. To identify novel BRD4 inhibitors from natural products, a hierarchical virtual screening method including pharmacophore modeling, molecular docking, and molecular dynamic simulation was performed to obtain five hit compounds with potential BRD4 inhibitory activity. Subsequently, structural optimization of the hit compound (ZINC2648030) with chromone structure was conducted to afford a series of derivatives (<b>8a</b>–<b>13e</b>), and their BRD4 inhibitory activities were evaluated. Among them, <b>13b</b> showed remarkable BRD4 inhibitory activity (IC<sub>50</sub> = 0.60 μM). Moreover, <b>13b</b> displayed a potent inhibitory effect on A549 cells with an IC<sub>50</sub> value of 0.79 μM, and further investigations demonstrated that it has the potential to induce apoptosis, inhibit colony formation, and suppress cell invasion. These findings indicated that <b>13b</b> might be a candidate for cancer treatment.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 3","pages":"720 - 744"},"PeriodicalIF":2.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481091","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

Olaparib research update: mechanism, structure and clinical trials 奥拉帕尼研究进展：机制、结构和临床试验

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-01-26 DOI: 10.1007/s00044-025-03375-8

Hao Che, Li-Wei Wang, Xiang-Yang Ye, Xingrui He

引用次数: 0

Uncaria-derived compounds for cancer treatment: mechanistic insights and therapeutic potential 用于癌症治疗的钩藤衍生化合物：机制见解和治疗潜力

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-01-26 DOI: 10.1007/s00044-025-03370-z

Zhichao Wang, Shi Xiang, Wenwen Zhang, Hui Chen, Chao Yang

{"title":"Uncaria-derived compounds for cancer treatment: mechanistic insights and therapeutic potential","authors":"Zhichao Wang, Shi Xiang, Wenwen Zhang, Hui Chen, Chao Yang","doi":"10.1007/s00044-025-03370-z","DOIUrl":"10.1007/s00044-025-03370-z","url":null,"abstract":"<div><p>Uncaria is a traditional medicinal plant belonging to the Rubiaceae family, with a particularly strong presence in Asia, Central America, and South America. Recent studies have indicated the potential of Uncaria-derived compounds, particularly alkaloids such as rhynchophylline and mitraphylline, as a means of cancer therapy. The objective of this review is to provide a comprehensive overview of the mechanistic insights into how these compounds exert anticancer effects, including their roles in apoptosis induction, cell cycle regulation, and modulation of key signaling pathways such as NF-κB and MAPK. Furthermore, we examine the capacity of Uncaria-derived compounds to augment the efficacy of conventional chemotherapeutics and their potential to mitigate adverse effects. Preclinical and clinical studies highlight the potential of Uncaria-derived compounds as a multifaceted approach to cancer treatment. Despite promising findings, further investigations are required to elucidate the full spectrum of their pharmacological activities, optimize dosage regimens, and assess long-term safety. This review emphasises the significance of Uncaria-derived compounds as a promising avenue for adjunctive cancer therapy, paving the way for future research and clinical applications.</p><div><figure><div><div><picture><img></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 3","pages":"517 - 534"},"PeriodicalIF":2.6,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-025-03370-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480956","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, synthesis and antifungal study of novel 2-aryl-3,4-dihydroisoquinolin-2-ium salts containing benzoate moieties 新型苯甲酸酯基2-芳基-3,4-二氢异喹啉-2-ium盐的设计、合成及抗真菌研究

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-01-22 DOI: 10.1007/s00044-025-03372-x

Wei Chen, Yanxi Jin, Luyao Wang

{"title":"Design, synthesis and antifungal study of novel 2-aryl-3,4-dihydroisoquinolin-2-ium salts containing benzoate moieties","authors":"Wei Chen, Yanxi Jin, Luyao Wang","doi":"10.1007/s00044-025-03372-x","DOIUrl":"10.1007/s00044-025-03372-x","url":null,"abstract":"<div><p>To discover natural-derived fungicides, three series of 2-aryl-3,4-dihydroisoquinolinium salts (<b>6</b>–<b>8</b>) containing benzoate moieties were designed and synthesized based-on quaternary isoquinoline alkaloids. Their structures were confirmed by spectroscopic analysis. Antifungal activities against 10 phytopathogenic fungi were evaluated in vitro at 50 mg/L. Most of the title compounds exhibited moderate to excellent fungicidal activities, which were as active as the positive controls (chlorothalonil, carbendazim) and better than the reference model <b>9</b>. Furthermore, for <i>R. solani</i> and <i>R. cerealis</i> <b>8c</b> presented EC<sub>50</sub> values of 5.03 and 7.41 mg/L, respectively, equal to or <span>superior</span> than chlorothalonil (4.63 mg/L, 15.0313 mg/L). The SARs studies indicated that introduce the benzoate moieties had significant effect on the antifungal activity, in which the presence of 3′-CO<sub>2</sub>Me (<b>7</b>) and 4′-CO<sub>2</sub>Me (<b>8</b>) derivatives were more active than 2′-CO<sub>2</sub>Me ones (<b>6</b>). Further mechanism studies on <i>R. solani</i> elucidated that compound <b>8c</b> could increase the permeability of the cell membrane, dramatically induce the accumulation of ROS. These results revealed that compound <b>8c</b> could represent as a potential lead for the development of antifungal agents.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 3","pages":"709 - 719"},"PeriodicalIF":2.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480928","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 insecticidal activities of novel m-diamide compounds containing n-propyl group 新型含正丙基间二胺化合物的设计、合成及其杀虫活性

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-01-21 DOI: 10.1007/s00044-025-03374-9

Daoxin Wu, Bingqing Li, Jiyong Liu, Tingting Zhao, Juncheng Xiang, Kangming Li

{"title":"Design, synthesis and insecticidal activities of novel m-diamide compounds containing n-propyl group","authors":"Daoxin Wu, Bingqing Li, Jiyong Liu, Tingting Zhao, Juncheng Xiang, Kangming Li","doi":"10.1007/s00044-025-03374-9","DOIUrl":"10.1007/s00044-025-03374-9","url":null,"abstract":"<div><p>To develop a structurally novel and efficient insecticide, a series of meta-diamide compounds incorporating <i>n</i>-propyl groups were designed and synthesized through active substructure splicing. This was achieved by using cyproflanilide as the lead compound while maintaining its fundamental active skeleton. All compounds were characterized by <sup>1</sup>H NMR, <sup>13</sup>C NMR, and HRMS. Preliminary bioassay results showed that some target compounds exhibited strong insecticidal activity against <i>Plutella xylostella</i>, <i>Mythimna separata</i>, and <i>Tetranychus cinnabarinus</i>. Notably, compound <b>7i</b> exhibited 100% lethality at a concentration of 1 mg/L against both <i>Plutella xylostella</i> and <i>Mythimna separata</i>; meanwhile, compound 7f achieved complete lethality against <i>Tetranychus cinnabarinus</i> at a concentration of 100 mg/L. These findings may provide valuable insights for developing novel, highly efficient meta-diamide compounds.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 3","pages":"700 - 708"},"PeriodicalIF":2.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481116","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

Synthesis and antibacterial activity of environmentally friendly sulfonium compounds 环境友好型磺胺类化合物的合成及其抑菌活性研究

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-01-18 DOI: 10.1007/s00044-024-03341-w

Jing Li, Wenyang Chen, Xinrui Bi, Yue Lin, Chengcai Liu, Yan Sun, Guinan Shen

{"title":"Synthesis and antibacterial activity of environmentally friendly sulfonium compounds","authors":"Jing Li, Wenyang Chen, Xinrui Bi, Yue Lin, Chengcai Liu, Yan Sun, Guinan Shen","doi":"10.1007/s00044-024-03341-w","DOIUrl":"10.1007/s00044-024-03341-w","url":null,"abstract":"<div><p>The abuse and overuse of antibacterial drugs have caused the increasing drug resistance of pathogenic bacteria, which threats human health and environmental health. Therefore the development of new environmentally friendly antibacterial drugs is of great urgency. The purpose of this study is to develop novel sulfonium compounds and evaluate their antibacterial activities. The sulfonium compounds were obtained by substitution reactions of methionine. The antimicrobial activities of the compounds were evaluated by measurement of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against <i>S. aureus</i> and <i>E. coli</i>. A total of fifteen sulfonium compounds were synthesized and all of them showed antibacterial activity that varied with the substitution chain length. These compounds were highly sensitive to <i>S. aureus</i> with the lowest MIC and MBC at 0.39 μmol/L and 1.56 μmol/L, respectively, which are lower than that of commercial quaternary ammonium compounds. An extra group of eight sulfonium compounds were also constructed to study the relationship between compound structures and their antibacterial abilities. A preferred structure with one longer hydrophobic alkyl chain at the amine position has been demonstrated for better antibacterial activity.</p><div><figure><div><div><picture><source><img></source></picture></div><div><p>Methionine based sulfonium compound as environmentally friendly antibacterial agent.</p></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 3","pages":"690 - 699"},"PeriodicalIF":2.6,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480910","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

Pancreatic lipase inhibitors as anti-obesity agents: a review of recent chemical scaffolds and their pancreatic lipase inhibitory potential 作为抗肥胖药物的胰脂肪酶抑制剂：近期化学支架及其胰脂肪酶抑制潜力的综述

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-01-18 DOI: 10.1007/s00044-025-03371-y

Noor ul Amin Mohsin, Matloob Ahmad, Maryam Farrukh, Sidra Rafique

引用次数: 0

Design, synthesis, in vitro evaluation, and molecular dynamics simulation studies of novel coumarin-acetohydrazide Schiff base derivatives as urease enzyme inhibitors 新型香豆素-乙酰肼希夫碱衍生物脲酶抑制剂的设计、合成、体外评价和分子动力学模拟研究

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-01-13 DOI: 10.1007/s00044-024-03369-y

Mohammad Azimi, Hassan Sepehrmansourie, Ahmad Ebadi, Gholamabbas Chehardoli, Mohammad Ali Zolfigol, Massoud Amanlou, Mohammad Nazari Montazer, Mohammad Mahdavi, Zahra Najafi

{"title":"Design, synthesis, in vitro evaluation, and molecular dynamics simulation studies of novel coumarin-acetohydrazide Schiff base derivatives as urease enzyme inhibitors","authors":"Mohammad Azimi, Hassan Sepehrmansourie, Ahmad Ebadi, Gholamabbas Chehardoli, Mohammad Ali Zolfigol, Massoud Amanlou, Mohammad Nazari Montazer, Mohammad Mahdavi, Zahra Najafi","doi":"10.1007/s00044-024-03369-y","DOIUrl":"10.1007/s00044-024-03369-y","url":null,"abstract":"<div><p>Urease inhibition, a nickel-containing metalloenzyme, is a promising approach for treating Helicobacter pylori (H. pylori) infections as a critical virulence factor that allows the bacteria to colonize the gastric mucosa and survive the acidic environment of the stomach. In this context, we report the design, synthesis, in vitro evaluation, and molecular dynamics simulation (MD) studies of novel ((4,7-dimethyl-2-oxo-2<i>H</i>-chromen-5-yl)oxy)acetohydrazide derivatives as urease enzyme inhibitors. Notably, all compounds exhibited potent inhibitory activities, with IC<sub>50</sub> values ranging from 2.438 µM to 4.427 µM. Further kinetic studies revealed that compound <b>11g</b> as the most potent compound with IC<sub>50</sub> value of 2.438 ± 0.31 μM acts as a non-competitive inhibitor toward urease with an inhibition constant (Ki) of 2.33 μM. In silico studies elucidated the binding interactions of compound <b>11g</b>, revealing crucial hydrogen bonds with key amino acid residues as well as chelation with Ni ions within the active site of urease. Molecular dynamics (MD) simulations confirmed the stable ligand-urease complex maintains interactions with both the active site residues and the flap moiety of urease, acting as noncompetitive inhibitors. These findings demonstrate the potential of coumarin-acetohydrazide Schiff base derivatives as a new frontier in developing urease inhibitors.</p></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 3","pages":"675 - 689"},"PeriodicalIF":2.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480997","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

In vitro and in silico studies on α-glucosidase inhibitory properties of bioactive components from the rhizomes of Alpinia officinarum Hance 高寒根茎生物活性成分抑制α-葡萄糖苷酶活性的体外和室内研究

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-01-07 DOI: 10.1007/s00044-024-03366-1

Zakhele Mphatsi Dlamini, Bongani Sicelo Dlamini, Shih-Han Fu, Ya-Lin Chang, Chi-Chien Lin, Yu-Kuo Chen, Kok-Tong Tan, Chi-I Chang

{"title":"In vitro and in silico studies on α-glucosidase inhibitory properties of bioactive components from the rhizomes of Alpinia officinarum Hance","authors":"Zakhele Mphatsi Dlamini, Bongani Sicelo Dlamini, Shih-Han Fu, Ya-Lin Chang, Chi-Chien Lin, Yu-Kuo Chen, Kok-Tong Tan, Chi-I Chang","doi":"10.1007/s00044-024-03366-1","DOIUrl":"10.1007/s00044-024-03366-1","url":null,"abstract":"<div><p>Key digestive enzymes, <i>α</i>-glucosidase and <i>α</i>-amylase, are associated with the occurrence of type 2 diabetes mellitus (T2DM). Inhibition of these important enzymes is one of the important strategies for the treatment of T2DM. In the search for alternative <i>α</i>-glucosidase inhibitors, five compounds (<b>1–5</b>) were obtained from the rhizomes of <i>Alpinia officinarum</i> Hance by chromatographic methods. In vitro enzyme inhibition assays, kinetic analysis, and molecular docking studies were conducted to investigate the inhibition mechanism of the isolated compounds against <i>α</i>-glucosidase. Compounds <b>1</b>, <b>3</b>, <b>4</b>, and <b>5</b> showed comparable <i>α</i>-glucosidase inhibitory activities to quercetin (IC<sub>50</sub> value of 19.77 µM) with IC<sub>50</sub> values ranging from 37.48 to 89.08 µM. According to the findings of the kinetic analysis, compounds <b>1</b>, <b>2</b>, and <b>4</b> were uncompetitive inhibitors, while compound <b>3</b> was a competitive inhibitor and compound <b>5</b> was a mixed-type inhibitor of <i>α</i>-glucosidase. In the computational investigation, hydrogen bonds served as the primary bond between the compounds and the amino acid residues. The results showed that <i>A. officinarum</i> might be a viable source of <i>α</i>-glucosidase inhibitors and antidiabetic agents.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 3","pages":"664 - 674"},"PeriodicalIF":2.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480875","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