Cardenolides and pentacyclic triterpenes isolated from Acokanthera oblongifolia leaves: their biological activities with molecular docking study

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Howaida I. Abd-Alla ◽  
Maha M. Soltan ◽  
Amal Z. Hassan ◽  
Hanan A. A. Taie ◽  
Heba M. Abo-Salem ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Topoisomerase I ◽  
Biological Activities ◽  
Molecular Docking Study ◽  
2D Nmr Spectroscopy ◽  
Binding Interaction ◽  
Pentacyclic Triterpenes ◽  
Chemical Structures ◽  
H5n1 Influenza

Abstract Pentacyclic triterpenes and cardenolides were isolated from Acokanthera oblongifolia leaves. Their chemical structures were determined based on comprehensive 1D and 2D NMR spectroscopy. Their MIC was determined against 12 microorganisms. Their exerted cytotoxicity on the immortalized normal cells, hTERT-RPE1 was assessed by the sulforhodamine-B assay. The viral inhibitory effects of compounds against Newcastle disease virus (NDV) and H5N1 influenza virus IV were evaluated. Four in vitro antioxidant assays were performed in comparison with BHT and trolox and a weak activity was exhibited. Acovenoside A was with potent against H5N1-IV and NDV with IC50 ≤ 3.2 and ≤ 2.1 μg/ml and SI values of 93.75 and 95.23%, respectively, in comparison to ribavirin. Its CC50 record on Vero cells was > 400 and 200 μg/ml, respectively. Acobioside A was the most active compound against a broad range of microbes while Pseudomonas aeruginosa was the most sensitive. Its MIC (0.07 μg/ml) was 1/100-fold of the recorded CC50 (7.1 μg/ml/72 h) against hTERT-RPE1. The molecular docking of compounds on human DNA topoisomerase I (Top1-DNA) and IV glycoprotein hemagglutinin were studied using MOE program. This study has introduced the cardenolides rather than triterpenoids with the best docking score and binding interaction with the active site of the studied proteins.

Synthesis, DFT Calculations, DNA Binding and Molecular Docking Studies on Biologically Active N-((3-(4-Methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)naphthyl Derivatives

2021 ◽  
Vol 6 (4) ◽  
pp. 292-301
Author(s):  
P.V. Sandhya ◽  
K.S. Femina ◽  
A.V. Pradeep
Keyword(s):  
Molecular Docking ◽  
Dna Binding ◽  
Biological Activities ◽  
Condensation Reaction ◽  
Geometry Optimization ◽  
Docking Study ◽  
Biologically Active ◽  
Molecular Docking Study ◽  
Binding Interaction

The biologically active pyrazole clubbed imino naphthyl derivatives have been designed and synthesized from 1-phenyl-3-methoxy phenyl-1H-pyrazol-4-carboxaldehyde and substituted naphthyl amines via acid catalyzed condensation reaction. All the synthesized compounds were well characterized by different spectroscopic and mass spectral techniques. The in vitro antibacterial, antifungal and antituberculosis studies were carried out. The molecular docking study was also done with the software Arguslab 4.0.1. The studied compounds showed moderate to good biological activities both experimentally and theoretically. Geometry optimization, DNA binding interaction and FMO analysis were also investigated with the help of Gaussian 16 package at B3LYP/6-31G(d,p) level.

Action of Thioglycosides of 1,2,4-Triazoles and Imidazoles on the Oxidative Stress and Glycosidases in Mice with Molecular Docking

2019 ◽  
Vol 16 (6) ◽  
pp. 696-710
Author(s):  
Mahmoud Balbaa ◽  
Doaa Awad ◽  
Ahmad Abd Elaal ◽  
Shimaa Mahsoub ◽  
Mayssaa Moharram ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Docking ◽  
Active Sites ◽  
Biological Activities ◽  
Imidazole Ring ◽  
Quantitative Structure Activity Relationship ◽  
Binding Interaction ◽  
Qsar Study

Background: ,2,3-Triazoles and imidazoles are important five-membered heterocyclic scaffolds due to their extensive biological activities. These products have been an area of growing interest to many researchers around the world because of their enormous pharmaceutical scope. Methods: The in vivo and in vitro enzyme inhibition of some thioglycosides encompassing 1,2,4- triazole N1, N2, and N3 and/or imidazole moieties N4, N5, and N6. The effect on the antioxidant enzymes (superoxide dismutase, glutathione S-transferase, glutathione peroxidase and catalase) was investigated as well as their effect on α-glucosidase and β-glucuronidase. Molecular docking studies were carried out to investigate the mode of the binding interaction of the compounds with α- glucosidase and β -glucuronidase. In addition, quantitative structure-activity relationship (QSAR) investigation was applied to find out the correlation between toxicity and physicochemical properties. Results: The decrease of the antioxidant status was revealed by the in vivo effect of the tested compounds. Furthermore, the in vivo and in vitro inhibitory effects of the tested compounds were clearly pronounced on α-glucosidase, but not β-glucuronidase. The IC50 and Ki values revealed that the thioglycoside - based 1,2,4-triazole N3 possesses a high inhibitory action. In addition, the in vitro studies demonstrated that the whole tested 1,2,4-triazole are potent inhibitors with a Ki magnitude of 10-6 and exhibited a competitive type inhibition. On the other hand, the thioglycosides - based imidazole ring showed an antioxidant activity and exerted a slight in vivo stimulation of α-glucosidase and β- glucuronidase. Molecular docking proved that the compounds exhibited binding affinity with the active sites of α -glucosidase and β-glucuronidase (docking score ranged from -2.320 to -4.370 kcal/mol). Furthermore, QSAR study revealed that the HBD and RB were found to have an overall significant correlation with the toxicity. Conclusion: These data suggest that the inhibition of α-glucosidase is accompanied by an oxidative stress action.

Potential Bioactive glycosylated flavonoids as SARS-CoV-2 Main protease Inhibitors: A molecular Docking Study

2020 ◽  
Author(s):  
sabri ahmed cherrak ◽  
merzouk hafida ◽  
mokhtari soulimane nassima
Keyword(s):  
Molecular Docking ◽  
Data Bank ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Chemical Structures ◽  
In Vivo Experiments ◽  
Main Protease

A novel (COVID-19) responsible of acute respiratory infection closely related to SARS-CoV has recently emerged. So far there is no consensus for drug treatment to stop the spread of the virus. Discovery of a drug that would limit the virus expansion is one of the biggest challenges faced by the humanity in the last decades. In this perspective, testing existing drugs as inhibitors of the main COVID-19 protease is a good approach.Among natural phenolic compounds found in plants, fruit, and vegetables; flavonoids are the most abundant. Flavonoids, especially in their glycosylated forms, display a number of physiological activities, which makes them interesting to investigate as antiviral molecules.The flavonoids chemical structures were downloaded from PubChem and protease structure 6lu7 was from the Protein Data Bank site. Molecular docking study was performed using AutoDock Vina. Among the tested molecules Quercetin-3-O-rhamnoside showed the highest binding affinity (-9,7 kcal/mol). Docking studies showed that glycosylated flavonoids are good inhibitors for the covid-19 protease and could be further investigated by in vitro and in vivo experiments for further validation.

Synthesis of novel NSAIDs linked to triazolyl-oxadiazole heterocyclic compounds as more comprehensive antimicrobial agents: A computational molecular docking

2021 ◽  
Vol 17 ◽  
Author(s):  
Shaik Adamshafi ◽  
Venkatarao Veera ◽  
Mohan Rao SVM ◽  
Kishore Pilli VVN
Keyword(s):  
Molecular Docking ◽  
Antifungal Activity ◽  
Active Site ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
Solubility Parameters ◽  
Diffusion Method ◽  
Binding Interaction ◽  
Protein Database ◽  
Chemical Structures

Introduction: Progress in the development of triazolyl-oxadiazoles is a bisphosphonate-700 inhibitor is still continuing with an outcome of the good scaffold as oxadiazole as well as triazoles individually for antibacterial activity. Hence, we proposed a suitable approach for the synthesis of dual heterocyclic analogues consisting of the therapeutically used non steroidal anti-inflammatory drugs in a combined form and evaluated for their antibacterial, antifungal activities, docking studies. Methods: The chemical structures were confirmed by various spectroscopic methods like IR, 1H NMR, 13C NMR, mass, and elemental analysis. The antibacterial, antifungal activity of these compounds was screened against Gram-positive, Gram-negative bacteria and fungal stains by agar well diffusion method. The crystal structure of S. aureus complexed with active site of bisphosphonate BPH-700 (2ZCS) was obtained from the Protein Database (PDB, http://www.rcsb.org). Molecular properties, drug likeness score, lipophilicity and solubility parameters by Molinspiration and Molsoft software. 7f (2-NO2, 5-Ome), 7g (3-Cl, 4-Cl), 7a (2-NO2) Results: Among the synthesised NSAID-triazolyl-oxadiazole containing 2-nitro-5-methoxy (7f), 3,4-dichloro (7g) derivatives were found to be high active antibacterial agents against S. aureus, E. coli with MICs 16, 19 μg/mL respectively. 2-nitro-5-methoxy (7f), 4-bromo (7h) and 2-nitro (7a) derivatives displayed superior antifungal activity against A. niger and MICs 56, 76, 130 μg/mL respectively. From molecular docking NSAID linked to 3,4-dichloro analogue (7g) revealed stronger binding interaction (ΔG =7.90 Kcal/Mol) with amino acids Asp49 (1.19 A˚), Arg45 (2.17 A˚), Lys17, Lys46 in the active site of S. aureus complexed with bisphosphonate Bph-700 (2ZCS). The compounds followed the Lipinski ‘Rule of five’ were synthesized for antimicrobial screening as oral bioavailable drugs/leads. Maximum drug likeness model score 0.49, 0.41 was found for compounds 7h, 7b. Conclusion: The present work, through simple synthetic approaches, led to the development of novel hybrids of triazole-oxadiazole pharmacophores that exhibited remarkable biological activities against different microorganisms. The compounds showed suitable drug like properties and are expected to present good bioavailability profile. Discussion: An efficient combination of molecular modeling and biological activity provided an insight into QSAR guide lines that could aid in further development of these derivatives.

scholarly journals Carbohydrate-based peptidomimetics targeting neuropilin-1: Synthesis, molecular docking study and in vitro biological activities

2016 ◽  
Vol 24 (21) ◽  
pp. 5315-5325 ◽  
Author(s):  
Mylène Richard ◽  
Alicia Chateau ◽  
Christian Jelsch ◽  
Claude Didierjean ◽  
Xavier Manival ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Biological Activities ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Neuropilin 1

scholarly journals Design of New Chlorochalcone Derivatives as Potential Breast Anticancer Compound Based on QSAR Analysis and Molecular Docking Study

2021 ◽  
Vol 20 (3) ◽  
Author(s):  
Anita Dwi Puspitasari ◽  
Harno Dwi Pranowo ◽  
Endang Astuti ◽  
Tutik Dwi Wahyuningsih
Keyword(s):  
Molecular Docking ◽  
Correlation Coefficient ◽  
Biological Activities ◽  
Basis Set ◽  
Log P ◽  
Anticancer Activities ◽  
Mcf7 Cells ◽  
Molecular Docking Study ◽  
Chemical Structures ◽  
Cox 2

Quantitative structure-activity relationships (QSAR) proposes a model that relates the biological activities of drugs to their chemical structures, and the interaction between the drug and its target enzyme is revealed by molecular docking research. These studies were conducted on chalcone to produce a model that could design highly potent breast anticancer MCF7 cells. The compounds were optimized using ab initio using a basis set 6-31G, then their descriptors calculated using this method. Genetic Function Algorithm (GFA) was used to select descriptors and build the model. One of the six models generated was found to be the best with internal and external squared correlation coefficient (R2) of 0.743 and 0.744, respectively, adjusted squared correlation coefficient (adjusted R2) of 0.700, Standard estimate of error (SEE) of 0.198, Fcalc/Ftable of 6.423, and Predicted residual sum of squares (PRESS) of 1.177. The QSAR equation is pIC50 = 3.869 + (1.427 x qC1) + (4. 027 x qC10) + (0.856 x qC15) - (35.900 x ELUMO) + (0.208 x Log P). Hence, it can predict the breast anticancer activities of new chlorochalcones A-F. The compound with the best prediction was chlorochalcone A with pIC50 2.65 and IC50 value of 2.26 μM. The chlorochalcones A-F were able to bind to the main amino acid residues, namely Arg120 and Tyr355, on the active site of the COX-2 enzyme. These results could serve as a model for designing novel chlorochalcone as inhibitors of COX-2 with higher breast anticancer activities. Keywords: Chlorochalcone, COX-2, QSAR, MCF-7, Molecular docking

scholarly journals Anticancer and molecular docking studies of some new pyrazole-1-carbothioamide nucleosides

2019 ◽  
Vol 9 (6) ◽  
pp. 4642-4648 ◽  
Keyword(s):  
Molecular Docking ◽  
Human Cancer ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Reference Drug ◽  
Human Cancer Cell Lines ◽  
Chemical Structures ◽  
Hct 116 ◽  
Mcf 7

Eight pyrazole-1-carbothioamide nucleosides were synthesized through conensation of 3-(4-aminophenyl)-pyrazole-1-carbothioamide derivative 2 with four aldoses (arabinose, mannose, glucose and galactose) and acetylation of the produced nucleosides 3a-d with acetic anhydride in pyridine at room temperature to give their corresponding acetyl derivatives 4a-d. Their chemical structures were confirmed by spectroscopic and elemental analysis. The antiproliferative activity was screened against various human cancer cell lines (MCF-7, HepG2 and HCT-116) in vitro; compound 4b showed a significant IC50 values (8.5±0.72 for MCF-7, 9.4±0.84 for HepG2 and 11.7±0.89 µg/ml for HCT-116) which were close to the reference drug 5-fluorouracil (5-FU). Molecular docking study was utilized to illustrate the ability of the more active compounds 3b and 4b to inhibit thymidylate synthase and compare the results with an antimetabolite drug used in cancer chemotherapy "Raltitrexed".

scholarly journals Synthesis, Cyclooxygenases Inhibition Activities and Interactions with BSA of N-substituted 1H-pyrrolo[3,4-c]pyridine-1,3(2H)-diones Derivatives

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2934 ◽  
Author(s):  
Edward Krzyżak ◽  
Dominika Szkatuła ◽  
Benita Wiatrak ◽  
Tomasz Gębarowski ◽  
Aleksandra Marciniak
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Serum Albumins ◽  
Molecular Docking Study ◽  
Binding Interaction ◽  
Ic50 Value ◽  
Cox 2 ◽  
Therapeutic Activities ◽  
Cox 1

Inhibition of cyclooxygenase is the way of therapeutic activities for anti-inflammatory pharmaceuticals. Serum albumins are the major soluble protein able to bind and transport a variety of exogenous and endogenous ligands, including hydrophobic pharmaceuticals. In this study, a novel N-substituted 1H-pyrrolo[3–c]pyridine-1,3(2H)-diones derivatives were synthesized and biologically evaluated for their inhibitory activity against cyclooxygenases and interactions with BSA. In vitro, COX-1 and COX-2 inhibition assays were performed. Interaction with BSA was studied by fluorescence spectroscopy and circular dichroism measurement. The molecular docking study was conducted to understand the binding interaction of compounds in the active site of cyclooxygenases and BSA. The result of the COX-1 and COX-2 inhibitory studies revealed that all the compounds potentially inhibited COX-1 and COX-2. The IC50 value was found similar to meloxicam. The intrinsic fluorescence of BSA was quenched by tested compounds due to the formation of A/E–BSA complex. The results of the experiment and molecular docking confirmed the main interaction forces between studied compounds and BSA were hydrogen bonding and van der Waals force.

scholarly journals Synthesis, Molecular Docking and Tyrosinase Inhibitory Activity of the Decorated Methoxy Sulfonamide Chalcones: in vitro Inhibitory Effects and the Possible Binding Mode

2021 ◽  
Vol 50 (9) ◽  
pp. 2603-2614
Author(s):  
Thawanrat Kobkeatthawin ◽  
Suchada Chantrapromma ◽  
Thitipone Suwunwong ◽  
Lydia Rhyman ◽  
Yee Siew Choong ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Inhibitory Activity ◽  
Kojic Acid ◽  
Spectral Characteristics ◽  
Binding Mode ◽  
Molecular Docking Study ◽  
Standard Drug ◽  
Tyrosinase Inhibitory Activity ◽  
Chemical Structures

In this study, a series of sulfonamide chalcones derivatives was synthesized and its chemical structures were confirmed by spectral characteristics. The synthesized compounds were evaluated for their tyrosinase inhibitory activities along with molecular docking study. The tyrosinase inhibitory results indicated that compounds 5b, 5c, 5f, 5g and 5h displayed the significant tyrosinase inhibitory activity and comparable to the standard drug (kojic acid). Compound 5c exhibits the most potent tyrosinase inhibition among the synthesized compounds with IC50 = 0.43±0.07 mM, L-DOPA as the substrate, and better than that of the standard kojic acid (IC50 = 0.60±0.20 mM). Molecular docking studies showed that the binding mode of some compounds is in the tyrosinase binding pocket surrounding the copper in the active site. The correlation between the docking results with IC50 values showed that the binding mode prediction of the test compounds would also be convincing. This comprehensive study allows for a possible mechanism for the antityrosinase activity of the sulfonamide chalcones. These sulfonamide chalcones bind to copper atoms of tyrosinase which responsible for the catalytic activity of tyrosinase. These compounds may be used as a lead for rational drug designing for the multi-functional tyrosinase inhibitor.

scholarly journals Biological Evaluation and Molecular Docking with In Silico Physicochemical, Pharmacokinetic and Toxicity Prediction of Pyrazolo[1,5-a]pyrimidines

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1431 ◽  
Author(s):  
Ahmed M. Naglah ◽  
Ahmed A. Askar ◽  
Ashraf S. Hassan ◽  
Tamer K. Khatab ◽  
Mohamed A. Al-Omar ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Biological Activities ◽  
Antimicrobial Properties ◽  
Docking Study ◽  
Biological Evaluation ◽  
Immunomodulatory Activity ◽  
Molecular Docking Study ◽  
Lipinski’S Rule

Pyrazolo[1,5-a]pyrimidines 5a–c, 9a–c and 13a–i were synthesized for evaluation of their in vitro antimicrobial properties against some microorganisms and their immunomodulatory activity. The biological activities of pyrazolo[1,5-a]pyrimidines showed that the pyrazolo[1,5-a]pyrimidines (5c, 9a, 9c, 13a, 13c, 13d, 13e and 13h) displayed promising antimicrobial and immunomodulatory activities. Studying the in silico predicted physicochemical, pharmacokinetic, ADMET and drug-likeness properties for the pyrazolo[1,5-a]pyrimidines 5a–c, 9a–c and 13a–i confirmed that most of the compounds (i) were within the range set by Lipinski’s rule of five, (ii) show higher gastrointestinal absorption and inhibition of some CYP isoforms, and (iii) have a carcinogenicity test that was predicted as negative and hERG test that presented medium risk. Moreover, the molecular docking study demonstrated that the compounds 5c, 9a, 9c, 13a, 13c, 13d, 13e and 13h are potent inhibitors of 14-alpha demethylase, transpeptidase and alkaline phosphatase enzymes. This study could be valuable in the discovery of a new series of drugs.

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