International Journal of Medicinal Chemistry最新文献_第2页

Correlation between Virtual Screening Performance and Binding Site Descriptors of Protein Targets. 虚拟筛选性能与蛋白靶点结合位点描述子的相关性研究。

International Journal of Medicinal Chemistry Pub Date : 2018-01-11 eCollection Date: 2018-01-01 DOI: 10.1155/2018/3829307

Jamal Shamsara

{"title":"Correlation between Virtual Screening Performance and Binding Site Descriptors of Protein Targets.","authors":"Jamal Shamsara","doi":"10.1155/2018/3829307","DOIUrl":"https://doi.org/10.1155/2018/3829307","url":null,"abstract":"Rescoring is a simple approach that theoretically could improve the original docking results. In this study AutoDock Vina was used as a docked engine and three other scoring functions besides the original scoring function, Vina, as well as their combinations as consensus scoring functions were employed to explore the effect of rescoring on virtual screenings that had been done on diverse targets. Rescoring by DrugScore produces the most number of cases with significant changes in screening power. Thus, the DrugScore results were used to build a simple model based on two binding site descriptors that could predict possible improvement by DrugScore rescoring. Furthermore, generally the screening power of all rescoring approach as well as original AutoDock Vina docking results correlated with the Maximum Theoretical Shape Complementarity (MTSC) and Maximum Distance from Center of Mass and all Alpha spheres (MDCMA). Therefore, it was suggested that, with a more complete set of binding site descriptors, it could be possible to find robust relationship between binding site descriptors and response to certain molecular docking programs and scoring functions. The results could be helpful for future researches aiming to do a virtual screening using AutoDock Vina and/or rescoring using DrugScore.","PeriodicalId":14082,"journal":{"name":"International Journal of Medicinal Chemistry","volume":"2018 ","pages":"3829307"},"PeriodicalIF":0.0,"publicationDate":"2018-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2018/3829307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35918299","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: 11

Usefulness of Urea as a Means of Improving the Solubility of Poorly Water-Soluble Ascorbyl Palmitate. 尿素作为提高难水溶性抗坏血酸棕榈酸盐溶解度手段的有效性。

International Journal of Medicinal Chemistry Pub Date : 2017-01-01 Epub Date: 2017-11-06 DOI: 10.1155/2017/4391078

Yutaka Inoue, Daichi Niiyama, Isamu Murata, Ikuo Kanamoto

引用次数: 5

Targeting Peroxisome Proliferator-Activated Receptors Using Thiazolidinediones: Strategy for Design of Novel Antidiabetic Drugs. 利用噻唑烷二酮靶向过氧化物酶体增殖物激活受体:新型降糖药的设计策略。

International Journal of Medicinal Chemistry Pub Date : 2017-01-01 Epub Date: 2017-06-05 DOI: 10.1155/2017/1069718

Neelaveni Thangavel, Mohammed Al Bratty, Sadique Akhtar Javed, Waquar Ahsan, Hassan A Alhazmi

{"title":"Targeting Peroxisome Proliferator-Activated Receptors Using Thiazolidinediones: Strategy for Design of Novel Antidiabetic Drugs.","authors":"Neelaveni Thangavel, Mohammed Al Bratty, Sadique Akhtar Javed, Waquar Ahsan, Hassan A Alhazmi","doi":"10.1155/2017/1069718","DOIUrl":"https://doi.org/10.1155/2017/1069718","url":null,"abstract":"Thiazolidinediones are a class of well-established antidiabetic drugs, also named as glitazones. Thiazolidinedione structure has been an important structural domain of research, involving design and development of new drugs for the treatment of type 2 diabetes. Extensive research on the mechanism of action and the structural requirements has revealed that the intended antidiabetic activity in type 2 diabetes is due to their agonistic effect on peroxisome proliferator-activated receptor (PPAR) belonging to the nuclear receptor super family. Glitazones have specific affinity to PPARγ, one of the subtypes of PPARs. Certain compounds under development have dual PPARα/γ agonistic activity which might be beneficial in obesity and diabetic cardiomyopathy. Interesting array of hybrid compounds of thiazolidinedione PPARγ agonists exhibited therapeutic potential beyond antidiabetic activity. Pharmacology and chemistry of thiazolidinediones as PPARγ agonists and the potential of newer analogues as dual agonists of PPARs and other emerging targets for the therapy of type 2 diabetes are presented. This review highlights the possible modifications of the structural components in the general frame work of thiazolidinediones with respect to their binding efficacy, potency, and selectivity which would guide the future research in design of novel thiazolidinedione derivatives for the management of type 2 diabetes.","PeriodicalId":14082,"journal":{"name":"International Journal of Medicinal Chemistry","volume":"2017 ","pages":"1069718"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/1069718","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35125444","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: 58

Design, Synthesis, and Cytotoxicity Evaluation of Novel Griseofulvin Analogues with Improved Water Solubility. 新型水溶性灰黄霉素类似物的设计、合成及细胞毒性评价。

International Journal of Medicinal Chemistry Pub Date : 2017-01-01 Epub Date: 2017-12-07 DOI: 10.1155/2017/7386125

Ahmed K Hamdy, Mahmoud M Sheha, Atef A Abdel-Hafez, Samia A Shouman

{"title":"Design, Synthesis, and Cytotoxicity Evaluation of Novel Griseofulvin Analogues with Improved Water Solubility.","authors":"Ahmed K Hamdy, Mahmoud M Sheha, Atef A Abdel-Hafez, Samia A Shouman","doi":"10.1155/2017/7386125","DOIUrl":"https://doi.org/10.1155/2017/7386125","url":null,"abstract":"Griseofulvin 1 is an important antifungal agent that has recently received attention due to its antiproliferative activity in mammalian cancer cells. Study of SAR of some griseofulvin analogues has led to the identification of 2'-benzyloxy griseofulvin 3, a more potent analogue which retards tumor growth through inhibition of centrosomal clustering. However, similar to griseofulvin 1, compound 3 exhibited poor aqueous solubility. In order to improve the poor water solubility, six new griseofulvin analogues 5-10 were synthesized and tested for their antiproliferative activity and water solubility. The semicarbazone 9 and aminoguanidine 10 analogues were the most potent against HCT116 and MCF-7 cell lines. In combination studies, compound 9 was found to exert synergistic effects with tamoxifen and 5-fluorouracil against MCF-7 and HCT116 cells proliferation, respectively. The flow cytometric analysis of effect of 9 on cell cycle progression revealed G2/M arrest in HCT116. In addition, compound 9 induced apoptosis in MCF-7 cells. Finally, all synthesized analogues revealed higher water solubility than griseofulvin 1 and benzyloxy analogue 3 in pH 1.2 and 6.8 buffer solutions.","PeriodicalId":14082,"journal":{"name":"International Journal of Medicinal Chemistry","volume":"2017 ","pages":"7386125"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/7386125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35762442","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: 5

Synthesis, Antimicrobial, and Computational Evaluation of Novel Isobutylchalcones as Antimicrobial Agents. 新型异丁基查尔酮抗菌药物的合成、抗菌及计算评价。

International Journal of Medicinal Chemistry Pub Date : 2017-01-01 Epub Date: 2017-12-26 DOI: 10.1155/2017/6873924

Afzal Basha Shaik, Rajendra Prasad Yejella, Shahanaaz Shaik

引用次数: 10

Fluorinated Adenosine A_2A Receptor Antagonists Inspired by Preladenant as Potential Cancer Immunotherapeutics. 受前驱体启发的氟化腺苷A2A受体拮抗剂作为潜在的癌症免疫治疗药物。

International Journal of Medicinal Chemistry Pub Date : 2017-01-01 Epub Date: 2017-10-19 DOI: 10.1155/2017/4852537

Gengyang Yuan, Tanner C Jankins, Christopher G Patrick, Phaethon Philbrook, Olivia Sears, Stephen Hatfield, Michail Sitkovsky, Neil Vasdev, Steven H Liang, Mary Jo Ondrechen, Michael P Pollastri, Graham B Jones

引用次数: 9

Biophysical Approaches Facilitate Computational Drug Discovery for ATP-Binding Cassette Proteins. 生物物理方法促进atp结合盒蛋白的计算药物发现。

International Journal of Medicinal Chemistry Pub Date : 2017-01-01 Epub Date: 2017-03-19 DOI: 10.1155/2017/1529402

Steven V Molinski, Zoltán Bozóky, Surtaj H Iram, Saumel Ahmadi

{"title":"Biophysical Approaches Facilitate Computational Drug Discovery for ATP-Binding Cassette Proteins.","authors":"Steven V Molinski, Zoltán Bozóky, Surtaj H Iram, Saumel Ahmadi","doi":"10.1155/2017/1529402","DOIUrl":"https://doi.org/10.1155/2017/1529402","url":null,"abstract":"Although membrane proteins represent most therapeutically relevant drug targets, the availability of atomic resolution structures for this class of proteins has been limited. Structural characterization has been hampered by the biophysical nature of these polytopic transporters, receptors, and channels, and recent innovations to in vitro techniques aim to mitigate these challenges. One such class of membrane proteins, the ATP-binding cassette (ABC) superfamily, are broadly expressed throughout the human body, required for normal physiology and disease-causing when mutated, yet lacks sufficient structural representation in the Protein Data Bank. However, recent improvements to biophysical techniques (e.g., cryo-electron microscopy) have allowed for previously \"hard-to-study\" ABC proteins to be characterized at high resolution, providing insight into molecular mechanisms-of-action as well as revealing novel druggable sites for therapy design. These new advances provide ample opportunity for computational methods (e.g., virtual screening, molecular dynamics simulations, and structure-based drug design) to catalyze the discovery of novel small molecule therapeutics that can be easily translated from computer to bench and subsequently to the patient's bedside. In this review, we explore the utility of recent advances in biophysical methods coupled with well-established in silico techniques towards drug development for diseases caused by dysfunctional ABC proteins.","PeriodicalId":14082,"journal":{"name":"International Journal of Medicinal Chemistry","volume":"2017 ","pages":"1529402"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/1529402","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34913137","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: 6

New Conjugates of Quinoxaline as Potent Antitubercular and Antibacterial Agents 喹诺啉的新结合物作为有效的抗结核和抗菌药物

International Journal of Medicinal Chemistry Pub Date : 2016-03-08 DOI: 10.1155/2016/6471352

R. Peraman, R. Kuppusamy, Sunil Kumar Killi, Y. P. Reddy

引用次数: 21

Changes in the Physicochemical Properties of Piperine/β-Cyclodextrin due to the Formation of Inclusion Complexes 包合物形成对胡椒碱/β-环糊精理化性质的影响

International Journal of Medicinal Chemistry Pub Date : 2016-02-22 DOI: 10.1155/2016/8723139

Toshinari Ezawa, Y. Inoue, Sujimon Tunvichien, Rina Suzuki, I. Kanamoto

{"title":"Changes in the Physicochemical Properties of Piperine/β-Cyclodextrin due to the Formation of Inclusion Complexes","authors":"Toshinari Ezawa, Y. Inoue, Sujimon Tunvichien, Rina Suzuki, I. Kanamoto","doi":"10.1155/2016/8723139","DOIUrl":"https://doi.org/10.1155/2016/8723139","url":null,"abstract":"Piperine (PP) is a pungent component in black pepper that possesses useful biological activities; however it is practically insoluble in water. The aim of the current study was to prepare a coground mixture (GM) of PP and β-cyclodextrin (βCD) (molar ratio of PP/βCD = 1/1) and subsequently evaluate the solubility of PP and physicochemical properties of the GM. DSC thermal behavior of the GM showed the absence of melting peak of piperine. PXRD profile of the GM exhibited halo pattern and no characteristic peaks due to PP and βCD were observed. Based on Job's plot, the PP/βCD complex in solution had a stoichiometric ratio of 1/1. Raman spectrum of the GM revealed scattering peaks assigned for the benzene ring (C=C), the methylene groups (CH2), and ether groups (C-O-C) of PP that were broaden and shifted to lower frequencies. SEM micrographs showed that particles in the GM were agglomerated and had rough surface, unlike pure PP and pure βCD particles. At 15 min of dissolution testing, the amount dissolved of PP in the GM was dramatically increased (about 16 times) compared to that of pure PP. Moreover the interaction between PP and βCD cavity was detected by 1H-1H NMR nuclear Overhauser effect spectroscopy NMR spectroscopy.","PeriodicalId":14082,"journal":{"name":"International Journal of Medicinal Chemistry","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75293726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 31

Design and Microwave Assisted Synthesis of Coumarin Derivatives as PDE Inhibitors 香豆素类PDE抑制剂的设计与微波辅助合成

International Journal of Medicinal Chemistry Pub Date : 2016-02-21 DOI: 10.1155/2016/9890630

M. Kumbar, R. Kamble, A. Kamble, S. R. Salian, S. Kumari, Ramya Nair, G. Kalthur, S. Adiga, D. J. Prasad

引用次数: 10