scholarly journals Antiaging, antioxidant flavonoids; synthesis, antimicrobial screening as well as 3D QSAR CoMFA models for the prediction of biological activity

2014 ◽  
Vol 39 (2) ◽  
pp. 191-199 ◽  
Author(s):  
Bilkis Jahan Lumbiny ◽  
Zhang Hui ◽  
M Azizul Islam
Keyword(s):  
Predictive Model ◽  
Biological Activities ◽  
3D Qsar ◽  
Biologically Active ◽  
Field Analysis ◽  
Contour Maps ◽  
Chemical Structures ◽  
Hydroxy Flavone ◽  
Bonding Characteristics ◽  
Better Than

Flavonoids, polyphenolic heteronuclear compounds which are naturally occurring antioxidants are widely used as antiaging substances. Synthesis of new naturally occuring organic compounds with basic skeleton of chalcones, flavones and oxygenated flavones and their antimicrobial activity were reported by this research group for long. Presently comparative molecular field analysis (CoMFA) implemented in Sybyl 7.3 was conducted on a series of substituted flavones. CoMFA is an effective computer implemented 3D QSAR technique deriving a correlation between set of the biologically active molecules and their 3D shape, electrostatic and hydrogen bonding characteristics employing both interactive graphics and statistical techniques. Evaluation of 38 compounds were served to establish the models with grid spacing (2.0 Å). CoMFA produced best predictive model for compound 1C (2 ? Phenyl ? 1,4 ? benzopyrone) and compound 2C (5 ? Fluoro ? 3?? hydroxy flavone ) among all. Model for compound 2C [r2 conv (no-validation) = 0.956, SEE = 0.211, F value = 111.054) is better than that of compound 1C [r2 conv (no-validation) = 0.955, SEE = 0.212, F value = 110.261) but comparing superimposed model 1C being suggested as the best predictive model. 3D contour maps were generated to correlate the biological activities with the chemical structures of the examined compounds and for further design. DOI: http://dx.doi.org/10.3329/jasbs.v39i2.17856 J. Asiat. Soc. Bangladesh, Sci. 39(2): 191-199, December 2013

Molecular Docking and 3D-QSAR Studies of 4-Phenylpiperidine Derivatives as μ-Opioid Agonists

2011 ◽  
Vol 361-363 ◽  
pp. 263-267 ◽  
Author(s):  
Ming Liu ◽  
Wen Xiang Hu ◽  
Xiao Li Liu
Keyword(s):  
Electrostatic Interactions ◽  
Biological Activities ◽  
3D Qsar ◽  
Qsar Model ◽  
Field Analysis ◽  
Qsar Studies ◽  
Chemical Structures ◽  
Opioid Agonists ◽  
Qsar Models ◽  
Leave One Out

A predictive 3D-QSAR model which correlates the biological activities with the chemical structures of a series of 4-phenylpiperidine derivatives as μ opioid agonists was developed by means of comparative molecular field analysis (CoMFA). The stabilities of the 3D-QSAR models were verified by the leave-one-out cross-validation method. Moreover, the predictive capabilities of the models were validated by an external test set. Best predictions were obtained with CoMFA standard model(q2=0.504, N=6, r2=0.968) which revealed how steric and electrostatic interactions contribute to agonists bioactivities, and provided us with important information to understand the interaction of agonists and μ opioid receptor .

scholarly journals GC-MS Assisted Phytoactive Chemical Compounds Identification and Profiling with Mineral Constituents from Biologically Active Extracts of Aerva javanica (Burm. f) Juss. ex Schult.

2018 ◽  
Vol 46 (2) ◽  
pp. 517-524
Author(s):  
Kandhan KARTHISHWARAN ◽  
Subban KAMALRAJ ◽  
Chelliah JAYABASKARAN ◽  
Shyam S. KURUP ◽  
Sabitha SAKKIR ◽  
...  
Keyword(s):  
Biological Activities ◽  
Radical Scavenging Activity ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Biologically Active ◽  
Scavenging Activity ◽  
Medicinal Uses ◽  
Chemical Structures ◽  
Aerial Parts ◽  
Mineral Constituents

Aerva javanica (Burm. f) Juss. ex Schult. (Family: Amaranthaceae) family is one of the traditional medicinal plant growing in the United Arab Emirates. Apart from studies related to some medicinal properties, phytochemical, GC MS compound characterization and biological activities still to be investigated. An experiment was conducted to determine the possible bioactive components with their chemical structures and elucidation of phytochemicals from the aerial parts of the plant. The macro and micro-mineral constituents and antioxidant activities were also evaluated. Aerial parts of A. javanica were extracted sequentially with hexane, chloroform, ethyl acetate, acetone, methanol by cold percolation method. Free radical scavenging and antioxidant properties of methanolic extract were evaluated by using in vitro antioxidant assays such as hydroxyl radical scavenging activity, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, superoxide radical scavenging activity and ABTS radical scavenging activity. Primary phytochemical and micro-macro element was tested using standard protocol. The chemical characterization was done with the help of Gas Chromatography-Mass Spectrometry (GC–MS), and the mass spectra of the total compounds in the extract were matched with the National Institute of Standard and Technology (NIST) library. Mineral constituents were identified and estimated by ICP-OES. Ninety-nine metabolites were obtained by GC-MS anslysis; indole was found to be major components followed by 2-Chlorallyl diethyldithiocarbamate (CDEC), Carbaril, Bis(2-ethylhexyl) phthalate, Quinoline, 4H-Cyclopenta[def]phenanthrene,2-[Bis(2-chloroethylamino)]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide, Phenobarbital, 1H-Indole, 2-methyl-, 2,3,7,8-Tetrachlorodibenzo-p-dioxin Disulfide, diphenyl. The presence of various bioactive compounds in the extract validates the traditional medicinal uses of this plant.

scholarly journals Docking and 3D QSAR Studies on p38α MAP Kinase Inhibitors

2011 ◽  
Vol 8 (4) ◽  
pp. 1596-1605
Author(s):  
Mohan Babu Jatavath ◽  
Sree Kanth Sivan ◽  
Yamini Lingala ◽  
Vijjulatha Manga
Keyword(s):  
Map Kinase ◽  
Kinase Inhibitors ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Three Dimensional ◽  
3D Qsar ◽  
Qsar Model ◽  
Chemotherapeutic Agents ◽  
Field Analysis ◽  
Qsar Studies

The p38 signaling cascade has emerged as an attractive target for the design of novel chemotherapeutic agents for the treatment of inflammatory diseases. Three dimensional quantitative structure- activity relationship (3D- QSAR) studies were performed on a series of 25, 2-aminothiazole analogs as inhibitors of p38α mitogen activated protein (MAP) kinase. The docking results provided a reliable conformational alignment scheme for the 3D-QSAR model. The 3D-QSAR model showed very good statistical results namely q2, r2and r2predvalues for both comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The CoMFA and CoMSIA models & docking results provided the most significant correlation of steric, electrostatic, hydrophobic,H-bond donor,H-bond acceptor fields with biological activities and the provided values were in good agreement with the experimental results. The information rendered from molecular modeling studies gave valuable clues to optimize the lead and design new potential inhibitors.

In Silico Design of New B-Raf Kinase Type-II Inhibitors Through Combined Molecular Modeling Studies

2019 ◽  
Vol 16 (5) ◽  
pp. 570-583
Author(s):  
Weineng Zhou ◽  
Shuai Lu ◽  
Yanmin Zhang ◽  
Lingfeng Yin ◽  
Lu Zhu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Molecular Modeling ◽  
Binding Site ◽  
Biological Activities ◽  
3D Qsar ◽  
Type Ii ◽  
Contour Maps ◽  
Raf Kinase ◽  
Linear Relationships ◽  
Qsar Models

Background:B-Raf has become an important and exciting therapeutic cancer target.Methods:In the present work, molecular modeling protocols like molecular docking, MM/GBSA calculations, 3D-QSAR and binding site detection were performed on a dataset of 41 Type II inhibitors. Molecular docking was applied to explore the detailed binding process between the inhibitors and B-Raf kinase. Furthermore, the good linear relationships between G-Scores and MM/GBSA calculated and the experimental activity were shown. The satisfactory CoMFA and CoMSIA were constructed based on the conformations obtained by molecular docking.Results:The key structural requirements for increasing biological activity were verified by analyzing 3D contour maps of the 3D-QSAR models. FTMap and SiteMap were also used to detect the more efficient active binding site.Conclusion:New inhibitors were synthesized and the biological activities were evaluated, the results further validated our design strategy.

scholarly journals 3D-QSAR Study of Indol-2-yl Ethanones Derivatives as Novel Indoleamine 2,3-Dioxygenase (IDO) Inhibitors

2012 ◽  
Vol 9 (4) ◽  
pp. 1753-1759 ◽  
Author(s):  
Kamlendra S. Bhadoriya ◽  
Shailesh V. Jain ◽  
Sanjaykumar B. Bari ◽  
Manish L. Chavhan ◽  
Kuldeep R. Vispute
Keyword(s):  
Nearest Neighbor ◽  
External Validation ◽  
3D Qsar ◽  
Qsar Model ◽  
Field Analysis ◽  
Qsar Study ◽  
Internal Validation ◽  
Contour Maps ◽  
Model Classification ◽  
Ido Inhibitors

3D-QSAR approach usingkNN-MFA was applied to a series of Indol-2-yl ethanones derivatives as novel IDO inhibitors. For the purpose, 22 compounds were used to develop models. To elucidate the structural properties required for IDO inhibitory activity, we report herek-nearest neighbor molecular field analysis (kNN-MFA)-based 3D-QSAR model for Indol-2-yl ethanones derivatives as novel IDO inhibitors. Overall model classification accuracy was 76.27% (q2= 0.7627, representing internal validation) in training set and 79.35% (pred_r2= 0.7935, representing external validation) in test set using sphere exclusion and forward as a method of data selection and variable selection, respectively. Contour maps using this approach showed that hydrophobic and steric effects dominantly determine binding affinities. The information rendered by 3D-QSAR model may lead to a better understanding of structural requirements of IDO inhibitors and can help in the design of novel potent molecules.

scholarly journals Virtual Screening, Biological Evaluation, and 3D-QSAR Studies of New HIV-1 Entry Inhibitors That Function via the CD4 Primary Receptor

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 3036 ◽  
Author(s):  
Chaozai Zhang ◽  
Huijun Zhang ◽  
Lina S. Huang ◽  
Siyu Zhu ◽  
Yan Xu ◽  
...  
Keyword(s):  
Biological Activities ◽  
Similarity Index ◽  
3D Qsar ◽  
Biological Evaluation ◽  
Rational Drug Design ◽  
Field Analysis ◽  
Qsar Studies ◽  
Entry Inhibitors ◽  
Primary Receptor ◽  
Hiv 1

Human immunodeficiency virus type 1 (HIV-1) is responsible for the majority of HIV infections worldwide, and we still lack a cure for this infection. Blocking the interaction of HIV-1 and its primary receptor CD4 is one strategy for identifying new anti-HIV-1 entry inhibitors. Here we report the discovery of a novel ligand that can inhibit HIV-1 entry and infection via CD4. Biological and computational analyses of this inhibitor and its analogs, using bioactivity evaluation, Rule of Five (RO5), comparative molecular field analysis (CoMFA)/comparative molecular similarity index analysis (CoMSIA) models, and three-dimensional quantitative structure-activity relationship (3D-QSAR), singled out compound 3 as a promising lead molecule for the further development of therapeutics targeting HIV-1 entry. Our study demonstrates an effective approach for employing structure-based, rational drug design techniques to identify novel antiviral compounds with interesting biological activities.

scholarly journals CoMFA and CoMSIA Studies on Inhibitors of HIV-1 Integrase - Bicyclic Pyrimidinones

2010 ◽  
Vol 7 (s1) ◽  
pp. S75-S84 ◽  
Author(s):  
V. Radhika ◽  
S. Sree Kanth ◽  
M. Vijjulatha
Keyword(s):  
Biological Activities ◽  
3D Qsar ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Field Analysis ◽  
Integrase Inhibitors ◽  
Inhibitory Potency ◽  
Similarity Indices ◽  
Qsar Models ◽  
Hiv 1

To understand the structural requirements of HIV-1 integrase inhibitors and to design new ligands against human HIV-1 integrase with enhanced inhibitory potency, a 3D QSAR (quantitative structure-activity relationship) study with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) for a dataset of 35 bicyclic pyrimidinones which are inhibitors of human HIV-1 integrase was performed. QSAR models were computed with Sybyl. The 3D QSAR model showed very good statistical result, namely q2, r2and r2predvalues were high for both CoMFA and CoMSIA. Based on the high values for q2and r2we are confident that the 3D QSAR model gives good predictions that may be used to design better HIV-1 integrase inhibitors. The CoMFA and CoMSIA models reveal that steric and electrostatic fields contribute significantly with biological activities of the studied compounds.

Silica gel Supported Boric tri-Sulfuric Anhydride (SiO2-BTSA): An Efficient Catalytic System for the Synthesis of Phloroglucide Analogs as Antimicrobial Agents

2021 ◽  
Vol 18 (4) ◽  
pp. 419-428
Author(s):  
Rahele Bargebid ◽  
Ali Khalafi-Nezhad ◽  
Kamiar Zomorodian ◽  
Mahkameh Moradi ◽  
Soghra Khabnadideh
Keyword(s):  
Silica Gel ◽  
Aromatic Compounds ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
Catalytic Amount ◽  
Biologically Active ◽  
Sulfuric Anhydride ◽  
Chemical Structures ◽  
Broth Microdilution Method

Background: Polyhydroxy aromatic compounds are one of the most important classes of phenolic compounds with different biological activities. Some important and biologically active phenol-based compounds have also been isolated from nature. Methods: An efficient procedure for the synthesis of polyhydroxy aromatic compounds (phloroglucide analogs) is described. In this procedure, a reaction took place between different 4-substituted phenols and 2,6-bis(hydroxymethyl) phenols. The reactions proceed in the presence of catalytic amount of silica gel supported boric tri-sulfuric anhydride (SiO2-BTSA) in excellent yields. Results: 16 compounds were synthesized (I1-I16). Chemical structures of all the compounds were confirmed by spectroscopic methods. We optimized the chemical reactions in the presence of different acidic catalysts, different solvents and also different temperatures. A catalytic amount of SiO2-BTSA in dichloroethane (DCE) was the best condition. Some of the synthesized compounds were screened for their antimicrobial activities. Antifungal and antibacterial activities of the synthesized compounds were evaluated by broth microdilution method as recommended by CLSI. Some of the tested compounds showed good in vitro biological properties. Conclusion: Our active compounds could introduce as good candidates for further studies as antimicrobial agents.

scholarly journals Bioactive compounds from an endophytic fungi Nigrospora aurantiaca

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Safwan Safwan ◽  
George Hsiao ◽  
Tzong-Huei Lee ◽  
Ching-Kuo Lee
Keyword(s):  
Bioactive Compounds ◽  
Endophytic Fungi ◽  
Spectroscopic Data ◽  
Biological Activities ◽  
Inhibitory Effect ◽  
Fungal Strain ◽  
Biologically Active ◽  
No Production ◽  
Chemical Structures ◽  
Melaleuca Leucadendra

Abstract Background Many groups of fungi live as an endophyte in plants. Both published and undiscovered bioactive compounds can be found in endophytic fungi. Various biological activities of bioactive compounds from endophytic fungi had been reported, including anti-inflammatory and anticancerous effects. The chemical investigation of biologically active compounds from endophytic fungi Melaleuca leucadendra Linn. have not yet been stated. Results One new compound, namely nigaurdiol (1), along with five known compounds, xyloketal K (2), bostrycin (3), deoxybostrycin (4), xylanthraquinone (5), and ergosterol (6), were isolated from the Melaleuca leucadendra Linn. associated fungal strain Nigrospora aurantiaca#TMU062. Their chemical structures were elucidated by spectroscopic data and compared with literature. All isolated compounds were evaluated for inhibitory effect of NO production in LPS-activated microglial BV-2 cells. Conclusions Compound 6 exhibited considerable inhibitory effect on NO production with IC50 values of 7.2 ± 1.4 µM and the survival rate of the cells was 90.8 ± 6.7% at the concentration of 10 µM.

scholarly journals 3D-QSAR, Molecular Docking, and Molecular Dynamics Simulation Study of Thieno[3,2-b]Pyrrole-5- Carboxamide Derivatives as LSD1 Inhibitors

2019 ◽  
Author(s):  
Meilan Huang ◽  
yongtao Xu ◽  
Zihao He ◽  
Min Yang ◽  
Hongyi Liu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Three Dimensional ◽  
3D Qsar ◽  
Quantitative Structure Activity Relationship ◽  
Field Analysis ◽  
Dynamics Simulation ◽  
Binding Modes ◽  
Binding Interaction ◽  
Contour Maps

Histone Lysine Specific Demethylase 1 (LSD1) is overexpressed in many cancers and become a new target for anticancer drugs. In recent years, the small molecule inhibitors with various structures targeting LSD1 have been reported. Here we report the binding interaction modes of a series of thieno[3,2-b]pyrrole-5-carboxamides LSD1 inhibitors using molecular docking, three dimensional quantitative structure-activity relationship (3D-QSAR). Comparative molecular field analysis (CoMFA q2=0.783, r2=0.944, r2pred=0.851) and Comparative molecular similarity indices analysis (CoMSIA q2=0.728, r2=0.982, r2pred=0.814) were used to establish 3D-QSAR models, which had good verification and prediction capabilities. Based on the contour maps and the information of molecular docking, 8 novel small molecules were designed in silico, among which compounds D4, D5 and D8 with high predictive activity were subjected to further molecular dynamics simulations (MD), and their possible binding modes were explored. It was found that Asn535 plays a crucial role in stabilizing the inhibitors. Furthermore, the ADME and bioavailability prediction for D4, D5 and D8 were carried out. The results would provide valuable guidance for designing new reversible LSD1 inhibitors in the future.

Sign in / Sign up

Export Citation Format

Share Document