International Journal of Medicinal Chemistry最新文献_第6页

Chemical characteristics, synthetic methods, and biological potential of quinazoline and quinazolinone derivatives. 喹唑啉及其衍生物的化学特性、合成方法及生物潜力。

International Journal of Medicinal Chemistry Pub Date : 2014-01-01 Epub Date: 2014-11-12 DOI: 10.1155/2014/395637

Mohammad Asif

引用次数: 136

Protective Effect of Selected Medicinal Plants against Hydrogen Peroxide Induced Oxidative Damage on Biological Substrates. 部分药用植物对过氧化氢诱导的生物基质氧化损伤的保护作用。

International Journal of Medicinal Chemistry Pub Date : 2014-01-01 Epub Date: 2014-11-12 DOI: 10.1155/2014/861084

Namratha Pai Kotebagilu, Vanitha Reddy Palvai, Asna Urooj

{"title":"Protective Effect of Selected Medicinal Plants against Hydrogen Peroxide Induced Oxidative Damage on Biological Substrates.","authors":"Namratha Pai Kotebagilu, Vanitha Reddy Palvai, Asna Urooj","doi":"10.1155/2014/861084","DOIUrl":"https://doi.org/10.1155/2014/861084","url":null,"abstract":"Oxidative stress is developed due to susceptibility of biological substrates to oxidation by generation of free radicals. In degenerative diseases, oxidative stress level can be reduced by antioxidants which neutralize free radicals. Primary objective of this work was to screen four medicinal plants, namely, Andrographis paniculata, Costus speciosus, Canthium parviflorum, and Abrus precatorius, for their antioxidant property using two biological substrates-RBC and microsomes. The antioxidative ability of three solvent extracts, methanol (100% and 80%) and aqueous leaf extracts, was studied at different concentrations by thiobarbituric acid reactive substances method using Fenton's reagent to induce oxidation in the substrates. The polyphenol and flavonoid content were analyzed to relate with the observed antioxidant effect of the extracts. The phytochemical screening indicated the presence of flavonoids, polyphenols, tannins, and β-carotene in the samples. In microsomes, 80% methanol extract of Canthium and Costus and, in RBC, 80% methanol extract of Costus showed highest inhibition of oxidation and correlated well with the polyphenol and flavonoid content. From the results it can be concluded that antioxidants from medicinal plants are capable of inhibiting oxidation in biological systems, suggesting scope for their use as nutraceuticals. ","PeriodicalId":14082,"journal":{"name":"International Journal of Medicinal Chemistry","volume":"2014 ","pages":"861084"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/861084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32848783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Molecular Modeling Studies of Thiophenyl C-Aryl Glucoside SGLT2 Inhibitors as Potential Antidiabetic Agents. 噻吩基c -芳基葡萄糖苷SGLT2抑制剂作为潜在降糖药的分子模拟研究。

International Journal of Medicinal Chemistry Pub Date : 2014-01-01 Epub Date: 2014-12-10 DOI: 10.1155/2014/739646

Mukesh C Sharma, Smita Sharma

{"title":"Molecular Modeling Studies of Thiophenyl C-Aryl Glucoside SGLT2 Inhibitors as Potential Antidiabetic Agents.","authors":"Mukesh C Sharma, Smita Sharma","doi":"10.1155/2014/739646","DOIUrl":"https://doi.org/10.1155/2014/739646","url":null,"abstract":"A QSAR study on thiophenyl derivatives as SGLT2 inhibitors as potential antidiabetic agents was performed with thirty-three compounds. Comparison of the obtained results indicated the superiority of the genetic algorithm over the simulated annealing and stepwise forward-backward variable method for feature selection. The best 2D QSAR model showed satisfactory statistical parameters for the data set (r (2) = 0.8499, q (2) = 0.8267, and pred_r (2) = 0.7729) with four descriptors describing the nature of substituent groups and the environment of the substitution site. Evaluation of the model implied that electron-rich substitution position improves the inhibitory activity. The good predictive 3D-QSAR models by k-nearest neighbor (kNN) method for molecular field analysis (MFA) have cross-validated coefficient q (2) value of 0.7663 and predicted r (2) value of 0.7386. The results have showed that thiophenyl groups are necessary for activity and halogen, bulky, and less bulky groups in thiophenyl nucleus enhanced the biological activity. These studies are promising for the development of novel SGLT2 inhibitor, which may have potent antidiabetic activity. ","PeriodicalId":14082,"journal":{"name":"International Journal of Medicinal Chemistry","volume":"2014 ","pages":"739646"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/739646","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32963686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Synthetic Antimicrobial Peptides Exhibit Two Different Binding Mechanisms to the Lipopolysaccharides Isolated from Pseudomonas aeruginosa and Klebsiella pneumoniae. 合成抗菌肽与铜绿假单胞菌和肺炎克雷伯菌分离的脂多糖的结合机制不同。

International Journal of Medicinal Chemistry Pub Date : 2014-01-01 Epub Date: 2014-12-28 DOI: 10.1155/2014/809283

Hanbo Chai, William E Allen, Rickey P Hicks

{"title":"Synthetic Antimicrobial Peptides Exhibit Two Different Binding Mechanisms to the Lipopolysaccharides Isolated from Pseudomonas aeruginosa and Klebsiella pneumoniae.","authors":"Hanbo Chai, William E Allen, Rickey P Hicks","doi":"10.1155/2014/809283","DOIUrl":"https://doi.org/10.1155/2014/809283","url":null,"abstract":"Circular dichroism and (1)H NMR were used to investigate the interactions of a series of synthetic antimicrobial peptides (AMPs) with lipopolysaccharides (LPS) isolated from Pseudomonas aeruginosa and Klebsiella pneumoniae. Previous CD studies with AMPs containing only three Tic-Oic dipeptide units do not exhibit helical characteristics upon interacting with small unilamellar vesicles (SUVs) consisting of LPS. Increasing the number of Tic-Oic dipeptide units to six resulted in five analogues with CD spectra that exhibited helical characteristics on binding to LPS SUVs. Spectroscopic and in vitro inhibitory data suggest that there are two possible helical conformations resulting from two different AMP-LPS binding mechanisms. Mechanism one involves a helical binding conformation where the AMP binds LPS very strongly and is not efficiently transported across the LPS bilayer resulting in the loss of inhibitory activity. Mechanism two involves a helical binding conformation where the AMP binds LPS very loosely and is efficiently transported across the LPS bilayer resulting in an increase in inhibitory activity. Mechanism three involves a nonhelical binding conformation where the AMP binds LPS very loosely and is efficiently transported across the LPS bilayer resulting in an increase in inhibitory activity. ","PeriodicalId":14082,"journal":{"name":"International Journal of Medicinal Chemistry","volume":"2014 ","pages":"809283"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/809283","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32993814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 14

A novel inhibitor of Mammalian triosephosphate isomerase found by an in silico approach. 一种新的哺乳动物三磷酸酯异构酶抑制剂。

International Journal of Medicinal Chemistry Pub Date : 2014-01-01 Epub Date: 2014-03-23 DOI: 10.1155/2014/469125

Lorraine Marsh, Kaushal Shah

{"title":"A novel inhibitor of Mammalian triosephosphate isomerase found by an in silico approach.","authors":"Lorraine Marsh, Kaushal Shah","doi":"10.1155/2014/469125","DOIUrl":"https://doi.org/10.1155/2014/469125","url":null,"abstract":"Triosephosphate isomerase (TIM) is an essential, highly conserved component of glycolysis. Tumors are often dependent on glycolysis for energy and metabolite production (the Warburg effect). Glycolysis inhibitors thus show promise as cancer treatments. TIM inhibition, unlike inhibition of other glycolysis enzymes, also produces toxic methylglyoxal targeted to regions of high glycolysis, an effect that might also be therapeutically useful. Thus TIM is an attractive drug target. A total of 338,562 lead-like molecules were analyzed computationally to find TIM inhibitors by an efficient \"double screen\" approach. The first fragment-sized compounds were studied using structure-based virtual screening to identify binding motifs for mammalian TIM. Subsequently, larger compounds, filtered to meet the binding criteria developed in the first analysis, were ranked using a second round of structure-based virtual screening. A compound was found that inhibited mammalian TIM in vitro in the micromolar range. Docking and molecular dynamics (MD) suggested that the inhibitor made hydrogen bond contacts with TIM catalytic residues. In addition, hydrophobic contacts were made throughout the binding site. All predicted inhibitor-TIM interactions involved TIM residues that were highly conserved. The discovered compound may provide a scaffold for elaboration of other inhibitors. ","PeriodicalId":14082,"journal":{"name":"International Journal of Medicinal Chemistry","volume":"2014 ","pages":"469125"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/469125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32804739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Experimental Design-Based Response Surface Methodology Optimization for Synthesis of β-Mercapto Carbonyl Derivatives as Antimycobacterial Drugs Catalyzed by Calcium Pyrophosphate. 基于实验设计的响应面法优化焦磷酸钙催化合成抗真菌药物β-巯基羰基衍生物。

International Journal of Medicinal Chemistry Pub Date : 2014-01-01 Epub Date: 2014-03-06 DOI: 10.1155/2014/586437

Younes Abrouki, Abdelkader Anouzla, Hayat Loukili, Jamal Bennazha, Rabiaâ Lotfi, Ahmed Rayadh, My Abdellah Bahlaoui, Saïd Sebti, Driss Zakarya, Mohamed Zahouily

{"title":"Experimental Design-Based Response Surface Methodology Optimization for Synthesis of β-Mercapto Carbonyl Derivatives as Antimycobacterial Drugs Catalyzed by Calcium Pyrophosphate.","authors":"Younes Abrouki, Abdelkader Anouzla, Hayat Loukili, Jamal Bennazha, Rabiaâ Lotfi, Ahmed Rayadh, My Abdellah Bahlaoui, Saïd Sebti, Driss Zakarya, Mohamed Zahouily","doi":"10.1155/2014/586437","DOIUrl":"https://doi.org/10.1155/2014/586437","url":null,"abstract":"A simple protocol for the efficient preparation of β-mercapto carbonyl derivatives as antimycobacterial drugs has been achieved via Thia-Michael reaction between chalcones derivatives and thiols in the presence of calcium pyrophosphate as a heterogeneous catalyst under mild reaction conditions. The central composite design was used to design an experimental program to provide data to model the effects of various factors on reaction yield (Y). The variables chosen were catalyst weight (X 1), reaction time (X 2), and solvent volume (X 3). The mathematical relationship of reaction yield on the three significant independent variables can be approximated by a nonlinear polynomial model. Predicted values were found to be in good agreement with experimental values. The optimum reaction conditions for reaction model (chalcone and thiophenol) obtained by response surface were applied to other substrates. This procedure provides several advantages such as high yield, clean product formation, and short reaction time. ","PeriodicalId":14082,"journal":{"name":"International Journal of Medicinal Chemistry","volume":"2014 ","pages":"586437"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/586437","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32804741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Evaluation of 11 scoring functions performance on matrix metalloproteinases. 基质金属蛋白酶11个评分函数的性能评价。

International Journal of Medicinal Chemistry Pub Date : 2014-01-01 Epub Date: 2014-12-25 DOI: 10.1155/2014/162150

Jamal Shamsara

{"title":"Evaluation of 11 scoring functions performance on matrix metalloproteinases.","authors":"Jamal Shamsara","doi":"10.1155/2014/162150","DOIUrl":"https://doi.org/10.1155/2014/162150","url":null,"abstract":"Matrix metalloproteinases (MMPs) have distinctive roles in various physiological and pathological processes such as inflammatory diseases and cancer. This study explored the performance of eleven scoring functions (D-Score, G-Score, ChemScore, F-Score, PMF-Score, PoseScore, RankScore, DSX, and X-Score and scoring functions of AutoDock4.1 and AutoDockVina). Their performance was judged by calculation of their correlations to experimental binding affinities of 3D ligand-enzyme complexes of MMP family. Furthermore, they were evaluated for their ability in reranking virtual screening study results performed on a member of MMP family (MMP-12). Enrichment factor at different levels and receiver operating characteristics (ROC) curves were used to assess their performance. Finally, we have developed a PCA model from the best functions. Of the scoring functions evaluated, F-Score, DSX, and ChemScore were the best overall performers in prediction of MMPs-inhibitors binding affinities while ChemScore, Autodock, and DSX had the best discriminative power in virtual screening against the MMP-12 target. Consensus scorings did not show statistically significant superiority over the other scorings methods in correlation study while PCA model which consists of ChemScore, Autodock, and DSX improved overall enrichment. Outcome of this study could be useful for the setting up of a suitable scoring protocol, resulting in enrichment of MMPs inhibitors. ","PeriodicalId":14082,"journal":{"name":"International Journal of Medicinal Chemistry","volume":"2014 ","pages":"162150"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/162150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32993872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 14

Therapeutic potential of hydrazones as anti-inflammatory agents. 肼作为抗炎剂的治疗潜力。

International Journal of Medicinal Chemistry Pub Date : 2014-01-01 Epub Date: 2014-03-04 DOI: 10.1155/2014/761030

Anu Kajal, Suman Bala, Neha Sharma, Sunil Kamboj, Vipin Saini

引用次数: 58

Structural Stereochemistry of Androstene Hormones Determines Interactions with Human Androgen, Estrogen, and Glucocorticoid Receptors. 雄烯激素的结构立体化学决定了与人类雄激素、雌激素和糖皮质激素受体的相互作用。

International Journal of Medicinal Chemistry Pub Date : 2013-03-14 DOI: 10.1155/2013/203606

Thomas L Shaak, Dayanjan S Wijesinghe, Charles E Chalfant, Robert F Diegelmann, Kevin R Ward, Roger M Loria

引用次数: 5

Novel Antimicrobial Agents: Fluorinated 2-(3-(Benzofuran-2-yl) pyrazol-1-yl)thiazoles. 新型抗菌剂:氟化2-(3-(苯并呋喃-2-基)吡唑-1-基)噻唑。

International Journal of Medicinal Chemistry Pub Date : 2013-01-01 Epub Date: 2013-09-11 DOI: 10.1155/2013/986536

Hanan A Mohamed, Ehab Abdel-Latif, Bakr F Abdel-Wahab, Ghada E A Awad

引用次数: 8