Medicinal Chemistry Research最新文献_第3页

Anticancer potential of nicotinonitrile derivatives as PIM-1 kinase inhibitors through apoptosis: in vitro and in vivo studies 烟腈衍生物作为PIM-1激酶抑制剂通过细胞凋亡的抗癌潜力：体外和体内研究

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-04-04 DOI: 10.1007/s00044-025-03392-7

Sara Salem Ali, Mohamed S. Nafie, Hanan A. Farag, Atef M. Amer

{"title":"Anticancer potential of nicotinonitrile derivatives as PIM-1 kinase inhibitors through apoptosis: in vitro and in vivo studies","authors":"Sara Salem Ali, Mohamed S. Nafie, Hanan A. Farag, Atef M. Amer","doi":"10.1007/s00044-025-03392-7","DOIUrl":"10.1007/s00044-025-03392-7","url":null,"abstract":"<div><p>Cytotoxicity of a series of nicotinonitrile-based derivatives with the molecular target and apoptosis activity against PC-3 cells was described. Compound <b>7b</b> exhibited remarkable cytotoxicity against MCF-7 and PC-3 cells with IC<sub>50</sub> values of 3.58 μM and 3.60 μM, respectively. Interestingly, compounds <b>4k</b> and <b>7b</b> had potent PIM-1 kinase inhibition with IC<sub>50</sub> values of 21.2 nM and 18.9 nM, respectively, with inhibition of 92.7 and 96.4% compared to Staurosporine (IC<sub>50</sub> = 16.7 nM, with 95.6% inhibition). Moreover, compound <b>7b</b> significantly activated apoptosis in PC-3 cells, increasing the apoptotic cell death, increasing total apoptosis by 34.21% compared to 0.9% in control cells, and arresting the cell cycle at the G1 pahse. In vivo model of SEC-bearing mice confirmed the anticancer activity of compound <b>7b</b> by having 42.9% compared to the 5-FU treatment of 54.2%; it maintained the physiological activity of hematological and biochemical parameters. Molecular docking effectively sheds insight into the mechanism of PIM-1 kinase inhibition by revealing the binding interactions between the lead chemical <b>7b</b> and the PIM-1 protein. The results showed that compound <b>7b</b> showed promise as a chemotherapeutic drug targeting PIM-1 for the treatment of breast cancer.</p></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 5","pages":"1074 - 1088"},"PeriodicalIF":2.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919030","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 biological evaluation of piperlongumine analogues containing indoline or tetrahydroquinoline as anticancer agents through apoptosis induction 含吲哚啉或四氢喹啉的胡椒隆明类似物通过诱导细胞凋亡的合成及生物学评价

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-03-31 DOI: 10.1007/s00044-025-03399-0

Kaili Chang, Chengyu Zhang, Xiuping Mao, Zixuan Tong, Liang Ma, Zi Liu, Guozheng Huang

{"title":"Synthesis and biological evaluation of piperlongumine analogues containing indoline or tetrahydroquinoline as anticancer agents through apoptosis induction","authors":"Kaili Chang, Chengyu Zhang, Xiuping Mao, Zixuan Tong, Liang Ma, Zi Liu, Guozheng Huang","doi":"10.1007/s00044-025-03399-0","DOIUrl":"10.1007/s00044-025-03399-0","url":null,"abstract":"<div><p>The investigation of natural products and their derivatives or analogues represents a critical avenue for the discovery of novel drug candidates. <i>Piperlongumine</i> (PL), a natural alkaloid, was originally isolated from the roots of <i>Piper longum</i> L., and has been reported to possess various biological activities. In this study, we designed and synthesized a total of 24 PL analogues by retaining the trimethoxystyryl group, whereas the piperidinone part of PL was replaced by indoline or 1,2,3,4-tetrahydroquinoline. The synthesized analogues were characterized by <sup>1</sup>H NMR, <sup>13</sup>C NMR, and HRMS analysis. The in vitro anticancer activity of the compounds against lung cancer cells A549, breast cancer cells MDA-MB-231 and liver cancer cells HepG2 were detected by MTT method. Notably, compound <b>13d</b> exhibited an IC<sub>50</sub> value of 8.97 ± 0.22 µM against HepG2 cells and showed selectivity towards human normal hepatocyte (LX-2, IC<sub>50</sub> = 49.88 ± 3.39 µM). In addition, morphological changes, cell growth curve and colony formation indicated that compound <b>13d</b> could significantly inhibit proliferation of HepG2 cells. Furthermore, Hoechst 33342 staining and flow cytometry confirmed that compound <b>13d</b> induced apoptosis in HepG2 cells, and activation of apoptosis markers caspase 3 and PARP was further observed via western blot analysis. Our study indicates that compound <b>13d</b> may be a potent lead candidate for cancer therapy against liver 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 5","pages":"1052 - 1064"},"PeriodicalIF":2.6,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919157","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

Hybrid-based design and biological evaluation of quinoline-benzoylhydrazine based derivatives as α-glucosidase inhibitors 喹啉-苯甲酰肼衍生物α-葡萄糖苷酶抑制剂的杂交设计与生物学评价

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-03-29 DOI: 10.1007/s00044-025-03394-5

Mehran Ghasemi, Aida Iraji, Maryam Dehghan, Mohammad Hashem Hashempur, Somayeh Mojtabavi, Mohammad Ali Faramarzi, Mohammad Mahdavi, Haleh Hamedifar, Mir H. Hajimiri, Ahmed Al-Harrasi

{"title":"Hybrid-based design and biological evaluation of quinoline-benzoylhydrazine based derivatives as α-glucosidase inhibitors","authors":"Mehran Ghasemi, Aida Iraji, Maryam Dehghan, Mohammad Hashem Hashempur, Somayeh Mojtabavi, Mohammad Ali Faramarzi, Mohammad Mahdavi, Haleh Hamedifar, Mir H. Hajimiri, Ahmed Al-Harrasi","doi":"10.1007/s00044-025-03394-5","DOIUrl":"10.1007/s00044-025-03394-5","url":null,"abstract":"<div><p>Diabetes mellitus, especially type 2 diabetes, is a metabolic disease that progresses with time and requires efficient management to avoid long-term problems. One promising approach to target Diabetes mellitus is to inhibit α-glucosidase to control postprandial hyperglycemia. In this work, new quinoline-benzoylhydrazine (<b>7a–m</b>) are designed, synthesized, and evaluated as possible α-glucosidase inhibitors. The Vilsmeier–Haack reaction was used in a multi-step process to synthesize the derivatives, and their inhibitory properties were evaluated. Kinetic analyses of the potent analog were conducted. Critical hydrogen bonding and π-π stacking interactions indicate the substantial binding affinity of the potent analog into the enzyme’s active site, as demonstrated by molecular docking and molecular mechanics with generalised born and surface area solvation (MM/GBSA) simulations. Furthermore, molecular dynamics simulations of the most potent analogs provided insights into their stability and interaction dynamics with the enzyme. These findings suggest that the designed derivatives are promising leads for developing novel α-glucosidase inhibitors to manage type 2 diabetes effectively.</p></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 5","pages":"1040 - 1051"},"PeriodicalIF":2.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919083","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 synthesis of O-glycoside derivatives with promising antidiabetic and anticancer potential 具有抗糖尿病和抗癌潜力的o -糖苷衍生物的设计与合成

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-03-29 DOI: 10.1007/s00044-025-03398-1

Utpal Dutta, Jumi Das, Manab Jyoti Goswami, Sakshi Bhardwaj, Akalesh Kumar Verma, Dwipen Kakati

{"title":"Design and synthesis of O-glycoside derivatives with promising antidiabetic and anticancer potential","authors":"Utpal Dutta, Jumi Das, Manab Jyoti Goswami, Sakshi Bhardwaj, Akalesh Kumar Verma, Dwipen Kakati","doi":"10.1007/s00044-025-03398-1","DOIUrl":"10.1007/s00044-025-03398-1","url":null,"abstract":"<div><p>Diabetes and cancer are significant global health challenges drawing continuous research efforts for the discovery and development of effective therapeutic agents. Chalcone serves as a fundamental structural component of flavonoids, continuing to fascinate medicinal chemists due to its exceptional biological activities. By implementing glycosylation as a post-synthetic modification, a series of chalcone-<i>O</i>-glucosides were synthesized, alongwith the assessment of their antidiabetic and anticancer potential. In-vitro antidiabetic potential of the glucosides was determined against the α-glucosidase enzyme and most of the compounds exhibited moderate to excellent inhibitory properties which was highest for the compound u92. The cytotoxic properties of the glucosides were examined in Dalton’s Lymphoma cancer cells. One-way ANOVA was used for data analysis at <i>P</i> ≤ 0.05 to validate the results. The compounds u25 and u79 exhibited maximum cytotoxic activity with minimum toxicity to the normal cells. The toxicity of these compounds was evaluated on normal peripheral blood mononuclear cells, enabling a comparative analysis of cellular responses in cancerous versus non-cancerous conditions. ADMET analysis and in silico pharmacophore model generation validated our findings, highlighting these glycosides as promising candidates for further research in developing antidiabetic agents and anticancer drugs targeting the selected cell line.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 5","pages":"1025 - 1039"},"PeriodicalIF":2.6,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919152","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

Correction: Design, synthesis, in vitro evaluation, and molecular dynamics simulation studies of novel coumarin-acetohydrazide Schiff base derivatives as urease enzyme inhibitors 修正：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 : 2025-03-29 DOI: 10.1007/s00044-025-03400-w

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

引用次数: 0

Naphthoquinones and tricyclic derivatives: in vitro evaluation as xanthine oxidase inhibitors 萘醌和三环衍生物：黄嘌呤氧化酶抑制剂的体外评价

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-03-28 DOI: 10.1007/s00044-025-03395-4

Stephanus J. Cloete, Roslyn Lefin, Jacobus P. Petzer, Anél Petzer

{"title":"Naphthoquinones and tricyclic derivatives: in vitro evaluation as xanthine oxidase inhibitors","authors":"Stephanus J. Cloete, Roslyn Lefin, Jacobus P. Petzer, Anél Petzer","doi":"10.1007/s00044-025-03395-4","DOIUrl":"10.1007/s00044-025-03395-4","url":null,"abstract":"<div><p>The enzyme, xanthine oxidase (XO), is a complex flavoprotein that catalyzes the sequential oxidation of hypoxanthine and xanthine to ultimately yield uric acid as the final steps in the catabolism of adenine nucleotides. In this process molecular oxygen is reduced to yield the superoxide anion radical and hydrogen peroxide. The overproduction of uric acid could lead to hyperuricemia and the deposition of urate crystals in joints and surrounding tissues. This condition is known as gout and is the most common cause of inflammatory arthritis. XO inhibitors are well-known treatment for the prevention of hyperuricemia and gout, and may find application in various other disease states that are associated with XO-induced production of reactive oxygen species. To discover new inhibitors of XO, the present study investigated 55 diverse compounds from an in-house library. The results showed that seven compounds inhibited bovine milk XO with IC<sub>50</sub> < 10 µM: juglone (IC<sub>50</sub> = 2.45 µM); menadione (IC<sub>50</sub> = 4.38 µM); benz(<i>g</i>)isoquinoline-5,10-dione (IC<sub>50</sub> = 2.07 µM); 2-chloro-7-methoxy-10<i>H</i>-phenothiazine (IC<sub>50</sub> = 2.17 µM); cinnabarinic acid (IC<sub>50</sub> = 3.41 µM); 9,10-phenanthrenequinone (IC<sub>50</sub> = 0.726 µM); quinalizarin (IC<sub>50</sub> = 8.54 µM). These potencies were comparable to that recorded for the reference inhibitor, chrysin (IC<sub>50</sub> = 13.6 µM). This study therefore discovered naphthoquinone and tricyclic derivatives as small molecule XO inhibitors for the development of treatments for hyperuricemia and other disorders that are associated with the overactivity of XO.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 5","pages":"1014 - 1024"},"PeriodicalIF":2.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-025-03395-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919080","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

Discovery of structurally novel tetrahydroisoquinoline derivatives bearing NO donor as potential anti-cancer therapeutics 发现结构新颖的含NO供体的四氢异喹啉衍生物作为潜在的抗癌药物

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-03-26 DOI: 10.1007/s00044-025-03396-3

Hao Chen, Xin Gao, Siqi Fan, Xiaodong Ma, Fang Fang

引用次数: 0

New amidrazone analogs as multi-kinase inhibitors: in-silico and biological investigation as an anticancer agent 新的氨基腙类似物作为多激酶抑制剂：作为抗癌剂的计算机和生物学研究

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-03-26 DOI: 10.1007/s00044-025-03397-2

Almeqdad Y. Habashneh, Mahmoud A. Al-Sha’er, Sanaa K. Bardaweel

{"title":"New amidrazone analogs as multi-kinase inhibitors: in-silico and biological investigation as an anticancer agent","authors":"Almeqdad Y. Habashneh, Mahmoud A. Al-Sha’er, Sanaa K. Bardaweel","doi":"10.1007/s00044-025-03397-2","DOIUrl":"10.1007/s00044-025-03397-2","url":null,"abstract":"<div><p>A series of novel biphenyl- and naphthyl-based amidrazone derivatives was synthesized and evaluated for anticancer activity against breast (MDA-MB-231) and colon (HL-60) cancer cell lines. Seven piperazine-containing derivatives exhibited significant anticancer effects with IC<sub>50</sub> values ranging from 7 to 30 μM while showing low toxicity toward fibroblasts (IC<sub>50</sub> > 300 μM). Molecular docking studies revealed that the most active compounds, <b>10a</b> and <b>10e</b>, bind strongly within the ATP-binding site of c-Abl kinase (PDB: 1IEP, resolution: 2.10 Å), achieving LibDock scores of 64.26 and 87.68, respectively, and enzyme inhibition IC<sub>50</sub> values of 18.29 μM and 10.28 μM. Compounds <b>12b, 12c, 12e</b>, and <b>15b</b> significantly inhibited PKN2 activity, while <b>12d</b> and <b>16d</b> showed enhanced potency against IKKβ despite lower c-Abl inhibition. These findings indicate that the anticancer effects of the synthesized derivatives are likely mediated by multitarget kinase inhibition, underscoring their promise as candidates for developing multi-kinase-targeting anticancer 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 5","pages":"996 - 1013"},"PeriodicalIF":2.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919299","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, hydrolysis, and COX-2/15-LOX inhibitory evaluation of 4-Acetamidophenyl 4-Bromobenzoates 4-乙酰氨基苯基4-溴苯甲酸酯的合成、水解及COX-2/15-LOX抑制评价

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-03-17 DOI: 10.1007/s00044-025-03393-6

Uzma Afzal, Abid Mahmood, Muhammad Zubair, Nasir Rasool, Aqsa Kanwal, Maria Sohail, Gulraiz Ahmad

{"title":"Synthesis, hydrolysis, and COX-2/15-LOX inhibitory evaluation of 4-Acetamidophenyl 4-Bromobenzoates","authors":"Uzma Afzal, Abid Mahmood, Muhammad Zubair, Nasir Rasool, Aqsa Kanwal, Maria Sohail, Gulraiz Ahmad","doi":"10.1007/s00044-025-03393-6","DOIUrl":"10.1007/s00044-025-03393-6","url":null,"abstract":"<div><p>The enzymes cyclooxygenase-2 (COX-2) and 15-lipoxygenase (15-LOX) metabolize arachidonic acid and have been associated with the onset and progression of several disorders, including various inflammatory diseases. Dual COX-2/15-LOX inhibition is a useful approach to develop drugs with enhanced biological activities and reduced off-target drug actions, with a wider range of anti-inflammatory properties as compared to traditional NSAIDs. In the current work, we designed and developed a number of arylated carboxylate acetaminophen analogues as COX-2/15-LOX dual inhibitors. Compounds <b>5b</b>, <b>5d</b>, and <b>5e</b> exhibited moderate COX-2 inhibitory activity (IC<sub>50</sub> = 1.44 ± 0.10, 1.80 ± 0.14, & 2.39 ± 0.11 µM) in vitro assay. Compound <b>5c</b> had higher COX-2 selectivity (IC<sub>50</sub> = 0.18 ± 0.05 µM) than celecoxib (IC<sub>50</sub> = 0.33 ± 011 µM). Compared to the quercetin (standard inhibitor), with an IC<sub>50</sub> = 15.8 ± 0.61 µM that all synthesized analogues exhibited significantly improved inhibitory activity towards 15-LOX and compound <b>5c</b> was found to be the most effective 15-LOX inhibitor (IC<sub>50</sub> = 0.14 ± 0.18 µM). Moreover, molecular docking closely aligns with in vitro studies, revealing the specific interactions towards synthesized derivatives (<b>5a</b>–<b>5f</b>) and target proteins.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 5","pages":"982 - 995"},"PeriodicalIF":2.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919148","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

Identification of the chemical composition of blue honeyberry leaves (Lonicera caerulea L. var. edulis) and their anti-inflammatory activity 蓝蜂蜜叶（Lonicera caerulea L. var. edulis）化学成分的鉴定及其抗炎活性

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2025-03-06 DOI: 10.1007/s00044-025-03391-8

Zhenji Rong, Chunping Yu, Xin Wang, Ruyue Wang, Yang Gao, Hailong Zhang

引用次数: 0