scholarly journals IN SILICO PREDICTION AND MOLECULAR DOCKING STUDIES OF BIOLOGICAL ACTIVITY OF HYDROACRIDINE (QUINOLINE) DERIVATIVES

2021 ◽  
Vol 87 (5) ◽  
pp. 38-52
Author(s):  
Nikolay Smetanin ◽  
Sofia Tokarieva ◽  
Svetlana Varenichenko ◽  
Oleg Farat ◽  
Victor Markov
Keyword(s):  
Free Energy ◽  
Biological Activity ◽  
Molecular Docking ◽  
Amino Acid ◽  
Hydrogen Bonds ◽  
Binding Free Energy ◽  
Moderate Activity ◽  
Amino Acid Residues ◽  
Anticonvulsant Agents ◽  
Anti Inflammatory

To find biological activity among easily available 2-[(4S,4’S/4R,4’R)-2’,5’-dioxo-2,3,5,6,7,8-hexahydro-1H-spiro[acridine-4,3’-pyrrolidin]-4’-yl]-N-aryl-acetamide, (4S/4R)-4-[(3R/3S)-1-(2-aryl)-2,5-dioxopyrrolidin-3-yl]-1,2,3,4,5,6,7,8-octahydroacridine-4-carbonitrile, (3S/4R)-3-[(3R/4S)-9-chloroacridine(quinoline)-4-yl]-1-N-aryl)pyrrolidine-2,5-diones. Methods: Organic synthesis, spectral methods, and molecular docking. We investigated by molecular docking the potential biological activity of previously synthesized compounds containing acridine and pyrrolidine-2,5-diones fragments in their structure, as well as synthesized in this work N’-hydroxy-1,2,3,4,5,6,7,8-octahydroacridine-4-carboximidamide. Based on the literature data, 3 directions of searching for the biological activity of the synthesized compounds have been chosen: cholinesterase inhibitors, anti-inflammatory, and anticonvulsant agents. As inhibitors of acetylcholinesterase and butylcholinesterase, substances with good binding free energy and hydrogen bonds with the desired amino acid residues of the Glu-His-Ser triad have been found among the tested compounds. The indicators of synthesized products have exceeded the literature data. The docking data for anti-inflammatory activity has revealed compounds with values above the docking data of the reference drugs - celecoxib and indomethacin. The compounds tested have shown moderate activity as anticonvulsant agents. 3-(7-bromo-9-chloro-1,2,3,4-tetrahydroacridin-4-yl)-1-(3-nitrophenyl)pyrrolidine-2,5-dione is potentially promising as an acetylcholinesterase inhibitor due to its high binding free energy (-13.7 kcal/mol) and hydrogen bonds with two amino acid residues Ser200, His440. Compound (4S/4R)-4-[(3R/3S)-1-(3-nitrophenyl)-2,5-dioxopyrrolidin-3-yl]-1,2,3,4,5,6,7,8-octahydroacridine-4-carbonitrile has proved to be the best as an anti-inflammatory agent. The presence of a pyrrolidine-2,5-diones fragment increases the indicators of the biological activity of the synthesized compounds in comparison with just acridine derivatives.

scholarly journals In Silico Study on N-Ferrocenylmethyl-N-Phenylpropionohydrazide and N-Ferrocenylmethyl-N-Pheylbenzohydrazide as Anticancer Drugs for Breast and Prostate Cancer

2018 ◽  
Vol 11 ◽  
pp. 17-25 ◽  
Author(s):  
Zegheb Nadjiba ◽  
Boubekri Chérifa ◽  
Touhami Lanez ◽  
Elhafnaoui Lanez
Keyword(s):  
Prostate Cancer ◽  
Free Energy ◽  
Molecular Docking ◽  
Hydrogen Bonds ◽  
Binding Free Energy ◽  
Docking Study ◽  
Dominant Mode ◽  
Molecular Docking Study ◽  
Docking Calculations ◽  
Breast And Prostate Cancer

Molecular docking calculations were used to evaluate the antitumor activities of N-ferrocenylmethyl-N-phenylpropanamide (FP) and N-ferrocenylmethyl-N-pheylbenzohydrazide (FH) against the enzymes of breast cancer 17-beta-hydroxysteroid dehydrogenase type 1 (17β-HSD1) and human steroidogenic cytochrome P450 17A1 prostate cancer mutant A105L (CYP17A1). The molecular docking study was performed using the open source AutoDock 4.2 software. The obtained results showed that both FP and FH bind with 17β-HSD1 and CYP17A1 via hydrogen bonds, binding free energy values for the adducts FH-17β-HSD1 and FH-CYP17A1 were respectively equal to-27.67 and-27.55 KJmol-1, while for the adducts FP-17β-HSD1 and FP-CYP17A1 they were respectively equal to-29.13 and 29.18 KJmol-1. The negative values and the magnitude of the obtained binding free energy indicated respectively the spontaneity and the electrostatic interaction of both ligands FP and FH with 17β-HSD1 and CYP17A1 receptors as the dominant mode. Finally the ligand FP binds more strongly to the receptor CYP17A1 and forms two respective hydrogen bonds with Arg96 and His373; this finding clearly indicate that FP is best qualified as potential drug candidature for breast and prostate cancer.

scholarly journals NUMBER OF RUNS VARIATIONS ON AUTODOCK 4 DO NOT HAVE A SIGNIFICANT EFFECT ON RMSD FROM DOCKING RESULTS

2021 ◽  
Vol 8 (6) ◽  
pp. 476-480
Author(s):  
M.R.F. Pratama ◽  
S. Siswandono
Keyword(s):  
Free Energy ◽  
Estrogen Receptor ◽  
Amino Acid ◽  
Hydrogen Bonds ◽  
Linear Equation ◽  
Significant Contribution ◽  
Amino Acid Residues ◽  
Maximum Difference ◽  
Binding Inhibition ◽  
Free Energy Of Binding

The aim. The number of runs in the docking process with AutoDock 4 is known to play an important role in the validity of the results obtained. The greater the number of runs it is often associated with the more valid docking results. However, it is not known exactly how the most ideal runs in the docking process with AutoDock 4. This study aims to determine the effect of the number of runs docking processes with AutoDock 4 on the validity of the docking results.Materials and methods. The method used is the redocking process with AutoDock 4.2.6. The receptor used is an estrogen receptor with ligand reference estradiol (PDB ID 1GWR). Variations were made on the number of runs from 10 to 100 in multiples of 10. The parameters observed were RMSD, free energy of binding, inhibition constants, amino acid residues, and the number of hydrogen bonds.Results. All experiments produce identical bond free energy, where the maximum difference in inhibition constant is only 0.06 nM. The lowest RMSD is indicated by the number of runs of 60, with a RMSD value of 0.942. There is no linear relationship between the number of runs and RMSD, with R in the linear equation of 0.4607.Conclusion. Overall, the number of runs does not show a significant contribution to the validity of the results of docking with AutoDock 4. However, these results have only been proven with the receptors used.

Biological Function and Chemistry of Endothelin. A Review

1999 ◽  
Vol 64 (8) ◽  
pp. 1211-1252 ◽  
Author(s):  
Jan Hlaváček ◽  
Renáta Marcová
Keyword(s):  
Biological Activity ◽  
Amino Acid ◽  
Biological Function ◽  
Biological Properties ◽  
Structural Basis ◽  
Amino Acid Residues ◽  
Snake Venoms ◽  
Vasoactive Peptides ◽  
Physico Chemical ◽  
Endothelin A

The first part of this review deals with the biosynthesis and a biological function of strongly vasoactive peptides named endothelins (ETs) including vasoactive intestinal contractor. Where it was useful, snake venoms sarafotoxins which are structural endothelin derivatives, were also mentioned. In the second part, an attention is paid to structural basis of the ETs biological activity, with respect to alterations of amino acid residues in the parent peptides modifying the conformation and consequently the physico-chemical and biological properties in corresponding ETs analogs. Special attention is focussed on the area of ETs receptors and their interaction with peptide and non peptide agonists and antagonists, important in designing selective inhibitors of ETs receptors potentially applicable as drugs in a medicine. A review with 182 references.

scholarly journals In Silico Prediction, Molecular Docking and Dynamics Studies of Steroidal Alkaloids of Holarrhena pubescens Wall. ex G. Don to Guanylyl Cyclase C: Implications in Designing of Novel Antidiarrheal Therapeutic Strategies

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4147
Author(s):  
Neha Gupta ◽  
Saurav Kumar Choudhary ◽  
Neeta Bhagat ◽  
Muthusamy Karthikeyan ◽  
Archana Chaturvedi
Keyword(s):  
Molecular Docking ◽  
Amino Acid ◽  
Guanylyl Cyclase ◽  
Extracellular Domain ◽  
Enterotoxigenic Escherichia Coli ◽  
Watery Diarrhea ◽  
Guanylyl Cyclase C ◽  
Amino Acid Residues ◽  
Lead Compounds

The binding of heat stable enterotoxin (STa) secreted by enterotoxigenic Escherichia coli (ETEC) to the extracellular domain of guanylyl cyclase c (ECDGC-C) causes activation of a signaling cascade, which ultimately results in watery diarrhea. We carried out this study with the objective of finding ligands that would interfere with the binding of STa on ECDGC-C. With this view in mind, we tested the biological activity of a alkaloid rich fraction of Holarrhena pubescens against ETEC under in vitro conditions. Since this fraction showed significant antibacterial activity against ETEC, we decided to test the screen binding affinity of nine compounds of steroidal alkaloid type from Holarrhena pubescens against extracellular domain (ECD) by molecular docking and identified three compounds with significant binding energy. Molecular dynamics simulations were performed for all the three lead compounds to establish the stability of their interaction with the target protein. Pharmacokinetics and toxicity profiling of these leads demonstrated that they possessed good drug-like properties. Furthermore, the ability of these leads to inhibit the binding of STa to ECD was evaluated. This was first done by identifying amino acid residues of ECDGC-C binding to STa by protein–protein docking. The results were matched with our molecular docking results. We report here that holadysenterine, one of the lead compounds that showed a strong affinity for the amino acid residues on ECDGC-C, also binds to STa. This suggests that holadysenterine has the potential to inhibit binding of STa on ECD and can be considered for future study, involving its validation through in vitro assays and animal model studies.

Metal complexes of polymers with amino acid residues. formation, stability and controlled biological activity

1990 ◽  
Vol 14 (1) ◽  
pp. 61-70 ◽  
Author(s):  
V.A. Lee ◽  
R.I. Musin ◽  
R.I. Tashmukhamedov ◽  
M.I. Shtilman ◽  
S.Sh. Rashidova
Keyword(s):  
Biological Activity ◽  
Amino Acid ◽  
Metal Complexes ◽  
Amino Acid Residues

Current Trends in Docking Methodologies

Oncology ◽  
2017 ◽  
pp. 829-847
Author(s):  
Shubhandra Tripathi ◽  
Akhil Kumar ◽  
Amandeep Kaur Kahlon ◽  
Ashok Sharma
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Binding Affinity ◽  
Binding Free Energy ◽  
Energy Calculation ◽  
Molecular Binding ◽  
New Horizons ◽  
Current Trends ◽  
Complex Scheme ◽  
Dynamics Simulations

Molecular docking was earlier considered to predict the binding affinity of the receptor and ligand molecules. With the progress in computational power and developing approaches, new horizons are now opening for accurate prediction of molecular binding affinity. In the current book chapter, recent strategies for Computer-Aided Drug Designing (CADD) including virtual screening and molecular docking, encompassing molecular dynamics simulations, and binding free energy calculation methods are discussed. Brief overview of different binding free energy methods MMPBSA, MMGBSA, LIE and TI have also been given along with the recent Relaxed Complex Scheme protocol.

scholarly journals Synthesis, characterization (IR, 1H, 13C & 31P NMR), fungicidal, herbicidal and molecular docking evaluation of steroid phosphorus compounds

2019 ◽  
Vol 17 (1) ◽  
pp. 621-628 ◽  
Author(s):  
Mahboob Alam ◽  
Youngwon Kim ◽  
Soonheum Park
Keyword(s):  
Molecular Docking ◽  
Binding Free Energy ◽  
Docking Study ◽  
Herbicidal Activity ◽  
Phosphorus Compounds ◽  
Moderate Activity ◽  
Spectroscopic Techniques ◽  
Molecular Docking Study ◽  
Mycelium Growth ◽  
Phosphorus Containing

AbstractPhosphorus containing steroidal derivatives such as 3β-oxo-[diazaphosphalidine-2’-one] stigmast-5-ene and 3β-oxo-[diazaphosphalidine-2’-one] stigmast-5,22-diene were designed, synthesized and characterized using spectroscopic techniques (IR, 1H, 13C & 31P NMR, HRMS) and elemental analysis. The fungicidal and herbicidal studies of the compounds were performed and the experimental outcomes showed that compound 4 showed a good fungicidal activity against mycelium growth of fungi, while in the case of herbicidal activity, both compounds show a moderate activity compared to the commercial drug; Atrazine. The binding free energy of active compound 4 to the receptor named 4-Hydroxyphenylpyruvate dioxygenase (HPPD) was calculated using the molecular docking study. The HPPD is one of the most effective targets of plants for the herbicide study.

The effect of modifications of the A5 and A19 amino acid residues on the biological activity of insulin. [Leu5-A] and [Phe19-A] sheep insulins

1983 ◽  
Vol 2 (2) ◽  
pp. 147-170 ◽  
Author(s):  
Nicolaos Ferderigos ◽  
G. Thompson Burke ◽  
Kouki Kitagawa ◽  
Panayotis G. Katsoyannis
Keyword(s):  
Biological Activity ◽  
Amino Acid ◽  
Amino Acid Residues
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