Medicinal Chemistry Research最新文献_第3页

Integrating omics data for personalized medicine in treating psoriasis 整合组学数据用于个体化治疗牛皮癣

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-11-27 DOI: 10.1007/s00044-024-03355-4

Manish Ramchandani, Amit Kumar Goyal

{"title":"Integrating omics data for personalized medicine in treating psoriasis","authors":"Manish Ramchandani, Amit Kumar Goyal","doi":"10.1007/s00044-024-03355-4","DOIUrl":"10.1007/s00044-024-03355-4","url":null,"abstract":"<div><p>Psoriasis is a chronic, multifactorial skin disorder characterized by the hyperproliferation of keratinocytes and persistent inflammation. It is driven by a complex interplay of genetic, immunological, and environmental factors. The heterogeneous nature of this disease presents significant challenges for effective diagnosis and treatment. Recent advancements in omics technologies such as genomics, transcriptomics, proteomics, and metabolomics have revolutionized our ability to understand the molecular basis of psoriasis. These technologies offer novel insights into disease mechanisms, identifying potential biomarkers for early diagnosis, disease progression, and therapeutic response. Further, longitudinal studies utilizing real-world patient data and advanced computational models will enable dynamic disease monitoring, offering prospects for predictive diagnostics and earlier intervention. As personalized treatment plans become more sophisticated, the evolution of omics-guided therapeutic strategies could revolutionize the standard of care in psoriasis, fostering a transition from reactive to preventative approaches. This review aims to elucidate the critical role of omics approaches in unraveling the intricate biological pathways involved in psoriasis and exploring how specific omics data serve as powerful tools for classifying patients and tailoring treatment options based on individual molecular profiles. Further, longitudinal studies utilizing real-world patient data and advanced computational models will enable dynamic disease monitoring, offering prospects for predictive diagnostics and earlier intervention. As personalized treatment plans become more sophisticated, the evolution of omics-guided therapeutic strategies could revolutionize the standard of care in psoriasis, fostering a transition from reactive to preventative approaches. Addressing current challenges in data integration and clinical applicability will be pivotal in advancing towards this future, with the potential to significantly improve patient outcomes and quality of life.</p></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 2","pages":"340 - 356"},"PeriodicalIF":2.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925749","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 assessment of triazolo-quinazoline carbothioamide derivatives for p38 MAP kinase inhibition: in-silico and in-vitro approaches 三唑-喹唑啉碳硫酰胺衍生物对p38 MAP激酶抑制的合成和生物学评价：硅内和体外方法

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-11-27 DOI: 10.1007/s00044-024-03348-3

CH Keerthi, Ramesh Kola, Divya Pingili, Archana Awasthi, DSNBK Prasanth, Chamakuri Kantlam

{"title":"Synthesis and biological assessment of triazolo-quinazoline carbothioamide derivatives for p38 MAP kinase inhibition: in-silico and in-vitro approaches","authors":"CH Keerthi, Ramesh Kola, Divya Pingili, Archana Awasthi, DSNBK Prasanth, Chamakuri Kantlam","doi":"10.1007/s00044-024-03348-3","DOIUrl":"10.1007/s00044-024-03348-3","url":null,"abstract":"<div><p>A series of 4-Alkyl-5-oxo-N-(pyridin-3-yl)-4,5-dihydro [1,2,3] triazolo[1,5-a] quinazoline-3-carbothioamide compounds (<b>8a-8k</b>) were synthesized as p38 MAP kinase inhibitors, which could potentially be used as anticancer agents. The synthesized compounds were assessed for their effectiveness in inhibiting cancer using the MCF-7 cancer cell line. The results showed that compound <b>8a</b> had the highest potency, with an IC<sub>50</sub> value of 39.76 ± 0.25 µM. Compound <b>8f</b> and <b>8d</b> exhibited noteworthy activity, with IC<sub>50</sub> values of 40.43 ± 2.04 µM and 42.15 ± 2.15 µM, respectively. Compound <b>8a</b> was found to effectively bind with the active site of p38α MAP kinase, with the PDB ID 1W7H. The docking score was found to be −8.8 kcal/mol. The ADME experiments, following Lipinski’s rule of five and Ergan’s egg graph, showed that all the synthesized compounds had excellent oral bioavailability and acceptable stomach absorption. Compound <b>8a</b> stood out as the most potent drug in the series, exhibiting considerable docking affinity, ADME profile, and p38 MAP kinase inhibitory action. The findings indicated that compound <b>8a</b> has promising p38 kinase inhibition and can be a possible therapeutic drug for further investigation.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 2","pages":"432 - 444"},"PeriodicalIF":2.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925750","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, stereochemical characterization, in vitro α-glucosidase, and α-amylase inhibition and in silico studies of novel pyrazole-hydrazide hydrazones 新型吡唑-肼腙的设计、合成、立体化学表征、α-葡萄糖苷酶和α-淀粉酶的体外抑制和硅研究

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-11-25 DOI: 10.1007/s00044-024-03335-8

Issam Ameziane El Hassani, Salma Mortada, Njabulo J. Gumede, Hamza Assila, Ali Alsalme, Afaf Oulmidi, My El Abbes Faouzi, Khalid Karrouchi, M’hammed Ansar

{"title":"Design, synthesis, stereochemical characterization, in vitro α-glucosidase, and α-amylase inhibition and in silico studies of novel pyrazole-hydrazide hydrazones","authors":"Issam Ameziane El Hassani, Salma Mortada, Njabulo J. Gumede, Hamza Assila, Ali Alsalme, Afaf Oulmidi, My El Abbes Faouzi, Khalid Karrouchi, M’hammed Ansar","doi":"10.1007/s00044-024-03335-8","DOIUrl":"10.1007/s00044-024-03335-8","url":null,"abstract":"<div><p>In this work, a novel series of fifteen pyrazole-linked hydrazide-hydrazone derivatives (<b>4a-o</b>) were designed, synthesized, characterized, and evaluated for their antihyperglycemic activity against α-amylase and α-glucosidase. In vitro results revealed that all synthesized compounds (4a-o) showed good to excellent antihyperglycemic activity with IC<sub>50</sub> in the range of 30.58 ± 0.56–290.70 ± 2.77 μM for α-glucosidase and in the range of 29.08 ± 0.56–160.70 ± 0.80 μM, as compared to the standard inhibitor acarbose (IC<sub>50(α-glucosidase)</sub> = 98.12 ± 2.10 µM and IC<sub>50(α-amylase)</sub> = 126.50 ± 2.01 µM). Among the series, compound <b>4m</b> with hydroxy group in <i>para</i> position at phenyl ring was also found as the most potent inhibitor of α-amylase and α-glucosidase with IC<sub>50</sub> values of 29.08 ± 0.86 and 30.58 ± 0.56 μM, respectively, indicating their better potency than the standard acarbose. In silico molecular docking and molecular dynamic simulations further confirmed the binding modes and binding affinities of compound <b>4m</b> and acarbose. The Structure-Activity Relationship (SAR) analysis of the effects of some functional groups in the co-structure of <b>4m</b> were confirmed by IFD and MDS for both α-amylase and α-glucosidase inhibitor recognition.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 1","pages":"252 - 271"},"PeriodicalIF":2.6,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142912935","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

α-Glucosidase inhibitory activities of aromatic compounds from the rhizomes of Alpinia galanga 高良姜根茎芳香族化合物α-葡萄糖苷酶抑制活性研究

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-11-23 DOI: 10.1007/s00044-024-03357-2

Yueh-Hung Cheng, Po-Chun Chen, Zakhele M. Dlamini, Jia-Wei Li, Bongani S. Dlamini, Yu-Kuo Chen, Chi-I Chang

{"title":"α-Glucosidase inhibitory activities of aromatic compounds from the rhizomes of Alpinia galanga","authors":"Yueh-Hung Cheng, Po-Chun Chen, Zakhele M. Dlamini, Jia-Wei Li, Bongani S. Dlamini, Yu-Kuo Chen, Chi-I Chang","doi":"10.1007/s00044-024-03357-2","DOIUrl":"10.1007/s00044-024-03357-2","url":null,"abstract":"<div><p>Inhibition of α-glucosidase is a widely recognized approach for managing hyperglycemia, particularly postprandial glucose spikes. In this study, the α-glucosidase inhibitory activity and interaction mechanisms of aromatic compounds isolated from the rhizomes of <i>Alpinia galanga</i> were investigated using the <i>p</i>-nitrophenol-α-D-glucopyranoside (<i>p</i>NPG) bioassay and molecular docking. The isolated aromatic compounds (<b>1</b>–<b>4</b>) showed significant α-glucosidase inhibitory activity with IC<sub>50</sub> values between 25 and 104 µM compared to the positive control acarbose (IC<sub>50</sub> = 1236.42 ± 1.30 µM). The experimental data showed that the most potent inhibitor of α-glucosidase (<i>E</i>)-<i>p</i>-coumaryl alcohol-γ-<i>O</i>-methyl ether (<b>3</b>) inhibited the enzyme via a mixed-type mechanism, with an IC<sub>50</sub> value of 25.00 ± 1.01 µM. Molecular docking indicated that compound <b>3</b> decreased the catalytic efficiency of α-glucosidase by competitively binding to the active pocket, thereby blocking the substrate. The binding activity is mainly mediated by hydrogen bonds and hydrophobic interactions. The results suggest that these aromatic compounds from <i>A. galanga</i> could serve as potential therapeutic agents for the control of postprandial hyperglycemia and the treatment of type 2 diabetes.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 2","pages":"466 - 475"},"PeriodicalIF":2.6,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925577","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

A fragment-based screen for inhibitors of Escherichia coli N5-CAIR mutase 基于片段的大肠杆菌 N5-CAIR 突变酶抑制剂筛选

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-11-23 DOI: 10.1007/s00044-024-03356-3

Marcella F. Sharma, Steven M. Firestine

{"title":"A fragment-based screen for inhibitors of Escherichia coli N5-CAIR mutase","authors":"Marcella F. Sharma, Steven M. Firestine","doi":"10.1007/s00044-024-03356-3","DOIUrl":"10.1007/s00044-024-03356-3","url":null,"abstract":"<div><p>Although purine biosynthesis is a primary metabolic pathway, there are fundamental differences between how purines are synthesized in microbes versus humans. In humans, the purine intermediate, 4-carboxy-5-aminoimidazole ribonucleotide (CAIR) is directly synthesized from 5-aminoimidazole ribonucleotide (AIR) and carbon dioxide by the enzyme AIR carboxylase. In bacteria, yeast and fungi, CAIR is synthesized from AIR via an intermediate N<sup>5</sup>-carboxyaminoimidazole ribonucleotide (N<sup>5</sup>-CAIR) by the enzyme N<sup>5</sup>-CAIR mutase. The difference in pathways between humans and microbes indicate that N<sup>5</sup>-CAIR mutase is a potential antimicrobial drug target. To identify inhibitors of <i>E. coli</i> N<sup>5</sup>-CAIR mutase, a fragment-based screening campaign was conducted using a thermal shift assay and a library of 4,500 fragments. Twenty-eight fragments were initially identified that displayed dose-dependent binding to N<sup>5</sup>-CAIR mutase with K<sub>d</sub> values ranging from 9–309 µM. Of the 28, 14 were obtained from commercial sources for retesting; however, only 5 showed dose-dependent binding to N<sup>5</sup>-CAIR mutase. The five fragments were assessed for their ability to inhibit enzyme activity. Four out of the 5 showed inhibition with K<sub>i</sub> values of 4.8 to 159 µM. All fragments contained nitrogen heterocycles with 3 out of the 4 containing 5-membered heterocycles like those found in the substrate of the enzyme. The identified fragments show similarities to compounds identified from studies on <i>B. anthracis</i> N<sup>5</sup>-CAIR mutase and human AIR carboxylase suggesting a common pharmacophore.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 12","pages":"2463 - 2475"},"PeriodicalIF":2.6,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826096","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

Oligonucleotides: evolution and innovation 寡核苷酸：演变与创新

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-11-21 DOI: 10.1007/s00044-024-03352-7

Amani A. Mohammed, Danah AlShaer, Othman Al Musaimi

{"title":"Oligonucleotides: evolution and innovation","authors":"Amani A. Mohammed, Danah AlShaer, Othman Al Musaimi","doi":"10.1007/s00044-024-03352-7","DOIUrl":"10.1007/s00044-024-03352-7","url":null,"abstract":"<div><p>Oligonucleotides, comprising single or double strands of RNA or DNA, are vital chemical compounds used in various laboratory and clinical applications. They represent a significant class of therapeutics with a rapidly expanding range of uses. Between 1998 and 2023, 19 oligonucleotides have received approval from the U.S. Food and Drug Administration (FDA). Their synthesis methods have undergone significant evolution over time. This review examines several oligonucleotide synthesis techniques, including phosphodiester, phosphotriester, and phosphoramidite approaches. It begins with a discussion of an early synthesis method involving a phosphoryl chloride intermediate, which proved unstable and prone to hydrolysis. The review then transitions to the solid-phase synthesis method, which uses polymer resins as a solid support, emphasizing its advantages over both phosphotriester and phosphoramidite techniques. This is followed by an exploration of recent advancements in oligonucleotide enzymatic synthesis, concluding with a discussion on modifications to bases, sugars, and backbones designed to improve their properties and therapeutic potential.</p></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 12","pages":"2204 - 2220"},"PeriodicalIF":2.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-024-03352-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826432","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

A guide for asymmetric synthesis of morphine alkaloids 吗啡生物碱的不对称合成指南

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-11-21 DOI: 10.1007/s00044-024-03350-9

Hui Zhao, Yunfei Cheng

引用次数: 0

Design, synthesis and antitumor activity evaluation of benzimidazole derivatives with potent HDAC inhibitory activity 具有强HDAC抑制活性的苯并咪唑衍生物的设计、合成及抗肿瘤活性评价

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-11-21 DOI: 10.1007/s00044-024-03349-2

Jiantao Ping, Hongrui Chu, Yisheng Zhao, Chen Chen

引用次数: 0

Phytochemical constituents isolated from Silene popovii Schischk 牡丹的植物化学成分分离

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-11-20 DOI: 10.1007/s00044-024-03345-6

Ugiloy Yu. Yusupova, Khayrulla M. Bobakulov, Alisher R. Khurramov, Vladimir N. Syrov, Feruza R. Egamova, Anas Karuth, Durbek A. Usmanov, Mohiuddin Quadir, Bakhtiyor Rasulev

引用次数: 0

Thiophene ring-opening reactions. Part VII: synthesis and antitumor, anti-inflammatory, and antioxidant properties of 1,3,4‒thiadiazoline‒6-sulfanylthiopyran-4(1H)-one hybrids 噻吩开环反应。第七部分：1,3,4 -噻二唑啉- 6-巯基硫代吡喃-4(1H)- 1杂合体的合成及其抗肿瘤、抗炎和抗氧化性能

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-11-18 DOI: 10.1007/s00044-024-03343-8

Shaima K. Alsawaleha, Jalal A. Zahra, Mustafa M. El-Abadelah, Violet Kasabri, Salim S. Sabri, Monther A. Khanfar

{"title":"Thiophene ring-opening reactions. Part VII: synthesis and antitumor, anti-inflammatory, and antioxidant properties of 1,3,4‒thiadiazoline‒6-sulfanylthiopyran-4(1H)-one hybrids","authors":"Shaima K. Alsawaleha, Jalal A. Zahra, Mustafa M. El-Abadelah, Violet Kasabri, Salim S. Sabri, Monther A. Khanfar","doi":"10.1007/s00044-024-03343-8","DOIUrl":"10.1007/s00044-024-03343-8","url":null,"abstract":"<div><p>The reaction of <i>N</i>′’(aryl)benzothiohydrazides with 2-chloro-6-((substituted)amino)-3-nitro-4-oxo-4H-thieno[2,3-b]thiopyran-5-carboxylate (<b>13</b>-<b>15</b>) under basic conditions (NEt<sub>3</sub>) in acetonitrile proceeds via thiophene ring-opening processes and yields, upon addition of iodomethane, the respective 1,3,4-thiadiazoline-6-sulfanylthiopyran-4(1<i>H</i>)-one hybrids. The new compounds were characterized by HRMS and NMR spectral data and confirmed by single-crystal X-ray crystallography. The cytotoxicity affinities for compounds <b>10</b>-<b>17</b> were evaluated in cross-correlations with their anti-inflammation and radical scavenging capacities. Compound <b>13</b> exhibited the highest cytotoxic properties, with IC<sub>50</sub> values ranging from 160 nM in mammary T47D to less than 20.35 µM in colorectal CACO2 among 12 diverse cancer monolayers. Compound <b>17c</b> significantly reduced lung and mammary cancer cell viability, with anti-tumorigenesis IC<sub>50</sub> values of less than 10 µM. These new compounds have the potential to be further optimized into novel selective cytotoxic treatments.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 2","pages":"392 - 405"},"PeriodicalIF":2.6,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925483","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