Pub Date : 2018-01-11eCollection Date: 2018-01-01DOI: 10.1155/2018/3829307
Jamal Shamsara
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.
{"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":"<p><p>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.</p>","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}
The aim of this study was to evaluate complexes of L-ascorbyl palmitate (ASCP) and urea (UR). This evaluation involved differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), near-infrared spectroscopy (NIR), a solubility test, a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging test, and a mushroom tyrosinase inhibition assay. Physicochemical evaluation revealed that ASCP/UR complexes form at a molar ratio of 1/12. The solubility test revealed that ASCP/UR complexes had increased solubility compared to ASCP. The DPPH radical scavenging test and mushroom tyrosinase inhibition assay revealed that the activity of ASCP/UR complexes was not impaired by complex formation. These results are probably due to the tetragonal crystal system of UR changing to a hexagonal crystal system and interaction with the alkyl group of ASCP.
{"title":"Usefulness of Urea as a Means of Improving the Solubility of Poorly Water-Soluble Ascorbyl Palmitate.","authors":"Yutaka Inoue, Daichi Niiyama, Isamu Murata, Ikuo Kanamoto","doi":"10.1155/2017/4391078","DOIUrl":"https://doi.org/10.1155/2017/4391078","url":null,"abstract":"<p><p>The aim of this study was to evaluate complexes of L-ascorbyl palmitate (ASCP) and urea (UR). This evaluation involved differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), near-infrared spectroscopy (NIR), a solubility test, a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging test, and a mushroom tyrosinase inhibition assay. Physicochemical evaluation revealed that ASCP/UR complexes form at a molar ratio of 1/12. The solubility test revealed that ASCP/UR complexes had increased solubility compared to ASCP. The DPPH radical scavenging test and mushroom tyrosinase inhibition assay revealed that the activity of ASCP/UR complexes was not impaired by complex formation. These results are probably due to the tetragonal crystal system of UR changing to a hexagonal crystal system and interaction with the alkyl group of ASCP.</p>","PeriodicalId":14082,"journal":{"name":"International Journal of Medicinal Chemistry","volume":"2017 ","pages":"4391078"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/4391078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35650964","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}
Pub Date : 2017-01-01Epub Date: 2017-06-05DOI: 10.1155/2017/1069718
Neelaveni Thangavel, Mohammed Al Bratty, Sadique Akhtar Javed, Waquar Ahsan, Hassan A Alhazmi
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.
{"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":"<p><p>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 PPAR<i>γ</i>, one of the subtypes of PPARs. Certain compounds under development have dual PPAR<i>α</i>/<i>γ</i> agonistic activity which might be beneficial in obesity and diabetic cardiomyopathy. Interesting array of hybrid compounds of thiazolidinedione PPAR<i>γ</i> agonists exhibited therapeutic potential beyond antidiabetic activity. Pharmacology and chemistry of thiazolidinediones as PPAR<i>γ</i> 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.</p>","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}
Pub Date : 2017-01-01Epub Date: 2017-12-07DOI: 10.1155/2017/7386125
Ahmed K Hamdy, Mahmoud M Sheha, Atef A Abdel-Hafez, Samia A Shouman
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.
{"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":"<p><p>Griseofulvin <b>1</b> 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 <b>3</b>, a more potent analogue which retards tumor growth through inhibition of centrosomal clustering. However, similar to griseofulvin <b>1</b>, compound <b>3</b> exhibited poor aqueous solubility. In order to improve the poor water solubility, six new griseofulvin analogues <b>5</b>-<b>10</b> were synthesized and tested for their antiproliferative activity and water solubility. The semicarbazone <b>9</b> and aminoguanidine <b>10</b> analogues were the most potent against HCT116 and MCF-7 cell lines. In combination studies, compound <b>9</b> 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 <b>9</b> on cell cycle progression revealed G2/M arrest in HCT116. In addition, compound <b>9</b> induced apoptosis in MCF-7 cells. Finally, all synthesized analogues revealed higher water solubility than griseofulvin <b>1</b> and benzyloxy analogue <b>3</b> in pH 1.2 and 6.8 buffer solutions.</p>","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}
A series of 25 new chalcones were synthesized by Claisen-Schmidt condensation, well characterized by spectroscopic data, and evaluated for their antibacterial and antifungal activities by serial tube dilution method. Among the compounds tested, A3 and A6 containing 2,4-dichlorophenyl and 2,4-difluorophenyl moiety, respectively, were found to be the most potent in the series against both bacterial and fungal strains with a MIC value of 16 µg/mL in each case. Further computational evaluation for antimicrobial activity was performed by atom based 3D-QSAR using PHASE™ software in order to have a correlation between the observed activities and predicted activities. The computational studies were in agreement with the in vitro antimicrobial results and had identified the most promising chalcones as antimicrobial agents and the responsible structural features for the proposed activity.
{"title":"Synthesis, Antimicrobial, and Computational Evaluation of Novel Isobutylchalcones as Antimicrobial Agents.","authors":"Afzal Basha Shaik, Rajendra Prasad Yejella, Shahanaaz Shaik","doi":"10.1155/2017/6873924","DOIUrl":"https://doi.org/10.1155/2017/6873924","url":null,"abstract":"<p><p>A series of 25 new chalcones were synthesized by Claisen-Schmidt condensation, well characterized by spectroscopic data, and evaluated for their antibacterial and antifungal activities by serial tube dilution method. Among the compounds tested, <b>A3</b> and <b>A6</b> containing 2,4-dichlorophenyl and 2,4-difluorophenyl moiety, respectively, were found to be the most potent in the series against both bacterial and fungal strains with a MIC value of 16 <i>µ</i>g/mL in each case. Further computational evaluation for antimicrobial activity was performed by atom based 3D-QSAR using PHASE™ software in order to have a correlation between the observed activities and predicted activities. The computational studies were in agreement with the <i>in vitro</i> antimicrobial results and had identified the most promising chalcones as antimicrobial agents and the responsible structural features for the proposed activity.</p>","PeriodicalId":14082,"journal":{"name":"International Journal of Medicinal Chemistry","volume":"2017 ","pages":"6873924"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/6873924","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35828877","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}
Pub Date : 2017-01-01Epub Date: 2017-10-19DOI: 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
Antagonism of the adenosine A2A receptor on T cells blocks the hypoxia-adenosinergic pathway to promote tumor rejection. Using an in vivo immunoassay based on the Concanavalin A mouse model, a series of A2A antagonists were studied and identified preladenant as a potent lead compound for development. Molecular modeling was employed to assist drug design and subsequent synthesis of analogs and those of tozadenant, including fluorinated polyethylene glycol PEGylated derivatives. The efficacy of the analogs was evaluated using two in vitro functional bioassays, and compound 29, a fluorinated triethylene glycol derivative of preladenant, was confirmed as a potential immunotherapeutic agent.
{"title":"Fluorinated Adenosine A<sub>2A</sub> Receptor Antagonists Inspired by Preladenant as Potential Cancer Immunotherapeutics.","authors":"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","doi":"10.1155/2017/4852537","DOIUrl":"https://doi.org/10.1155/2017/4852537","url":null,"abstract":"<p><p>Antagonism of the adenosine A<sub>2A</sub> receptor on T cells blocks the hypoxia-adenosinergic pathway to promote tumor rejection. Using an <i>in vivo</i> immunoassay based on the Concanavalin A mouse model, a series of A<sub>2A</sub> antagonists were studied and identified preladenant as a potent lead compound for development. Molecular modeling was employed to assist drug design and subsequent synthesis of analogs and those of tozadenant, including fluorinated polyethylene glycol PEGylated derivatives. The efficacy of the analogs was evaluated using two <i>in vitro</i> functional bioassays, and compound <b>29</b>, a fluorinated triethylene glycol derivative of preladenant, was confirmed as a potential immunotherapeutic agent.</p>","PeriodicalId":14082,"journal":{"name":"International Journal of Medicinal Chemistry","volume":"2017 ","pages":"4852537"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2017/4852537","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35307883","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}
Pub Date : 2017-01-01Epub Date: 2017-03-19DOI: 10.1155/2017/1529402
Steven V Molinski, Zoltán Bozóky, Surtaj H Iram, Saumel Ahmadi
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.
{"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":"<p><p>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.</p>","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}
R. Peraman, R. Kuppusamy, Sunil Kumar Killi, Y. P. Reddy
Considering quinoxaline as a privileged structure for the design of potent intercalating agents, some new sugar conjugates of quinoxaline were synthesized and characterized by IR, 1HNMR, 13C NMR, and mass spectral data. In vitro testing for antitubercular and antimicrobial activities was performed against Mycobacterium tuberculosis H 37 Rv and some pathogenic bacteria. Results revealed that conjugate containing ribose moiety demonstrated the most promising activity against Mycobacteria and bacteria with minimum inhibitory concentrations (MIC) of 0.65 and 2.07 μM, respectively. Other conjugates from xylose, glucose, and mannose were moderately active whilst disaccharides conjugates were found to be less active. In silico docking analysis of prototype compound revealed that ATP site of DNA gyrase B subunit could be a possible site for inhibitory action of these synthesized compounds.
{"title":"New Conjugates of Quinoxaline as Potent Antitubercular and Antibacterial Agents","authors":"R. Peraman, R. Kuppusamy, Sunil Kumar Killi, Y. P. Reddy","doi":"10.1155/2016/6471352","DOIUrl":"https://doi.org/10.1155/2016/6471352","url":null,"abstract":"Considering quinoxaline as a privileged structure for the design of potent intercalating agents, some new sugar conjugates of quinoxaline were synthesized and characterized by IR, 1HNMR, 13C NMR, and mass spectral data. In vitro testing for antitubercular and antimicrobial activities was performed against Mycobacterium tuberculosis H 37 Rv and some pathogenic bacteria. Results revealed that conjugate containing ribose moiety demonstrated the most promising activity against Mycobacteria and bacteria with minimum inhibitory concentrations (MIC) of 0.65 and 2.07 μM, respectively. Other conjugates from xylose, glucose, and mannose were moderately active whilst disaccharides conjugates were found to be less active. In silico docking analysis of prototype compound revealed that ATP site of DNA gyrase B subunit could be a possible site for inhibitory action of these synthesized compounds.","PeriodicalId":14082,"journal":{"name":"International Journal of Medicinal Chemistry","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79629675","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}
Toshinari Ezawa, Y. Inoue, Sujimon Tunvichien, Rina Suzuki, I. Kanamoto
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.
胡椒碱(PP)是黑胡椒中的一种刺激性成分,具有有益的生物活性;然而,它几乎不溶于水。本研究的目的是制备PP和β-环糊精(β - cd)的共混物(GM) (PP/βCD的摩尔比为1/1),随后评价了PP的溶解度和GM的理化性质。GM的DSC热行为显示没有胡椒碱的熔化峰。GM的PXRD谱表现为光晕型,未见PP和βCD的特征峰。根据Job图,溶液中PP/β - cd配合物的化学计量比为1/1。聚丙烯的拉曼光谱显示苯环(C=C)、亚甲基(CH2)和醚基(C- o -C)的散射峰变宽并移至较低的频率。SEM显微图显示,与纯PP和纯βCD颗粒不同,GM颗粒呈团聚状,表面粗糙。溶解测试15 min时,PP在GM中的溶解量较纯PP显著增加(约16倍),并通过1H-1H NMR核奥弗豪瑟效应谱检测PP与βCD空腔的相互作用。
{"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}
M. Kumbar, R. Kamble, A. Kamble, S. R. Salian, S. Kumari, Ramya Nair, G. Kalthur, S. Adiga, D. J. Prasad
Coumarins appended to benzimidazole through pyrazole are designed and synthesized using microwave irradiation. These compounds were analyzed for phosphodiesterase (PDE) inhibition indirectly by motility pattern in human spermatozoa. Some of the synthesized compounds, namely, 5d, 5e, 5f, 5g, 5h, and 5k, have exhibited potent inhibitory activity on PDE.
{"title":"Design and Microwave Assisted Synthesis of Coumarin Derivatives as PDE Inhibitors","authors":"M. Kumbar, R. Kamble, A. Kamble, S. R. Salian, S. Kumari, Ramya Nair, G. Kalthur, S. Adiga, D. J. Prasad","doi":"10.1155/2016/9890630","DOIUrl":"https://doi.org/10.1155/2016/9890630","url":null,"abstract":"Coumarins appended to benzimidazole through pyrazole are designed and synthesized using microwave irradiation. These compounds were analyzed for phosphodiesterase (PDE) inhibition indirectly by motility pattern in human spermatozoa. Some of the synthesized compounds, namely, 5d, 5e, 5f, 5g, 5h, and 5k, have exhibited potent inhibitory activity on PDE.","PeriodicalId":14082,"journal":{"name":"International Journal of Medicinal Chemistry","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75051303","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}