Comparison of 3-carbethoxy-4-phenyl-but-3-en-2-one and methylene quinuclidinone as a ligand to reactivate mutant p53: molecular docking study in three types of crystal structure mutant p53: 2BIM, 2JIY, and 2J21

2021 ◽  
pp. 3358-3364
Author(s):  
Jeffry Julianus ◽  
Jumina Jumina ◽  
Mustofa Mustofa
Keyword(s):  
Molecular Docking ◽  
Anticancer Agent ◽  
Docking Study ◽  
Binding Pocket ◽  
Mutant P53 ◽  
Cell Nuclei ◽  
Molecular Docking Study ◽  
Sh Group ◽  
Promising Ligand ◽  
Anticancer Compound

The existence of a large number of mutant p53 in cancer cell nuclei gives a poor prognosis. However, mutant p53 existence creates a challenge to design a new anticancer compound targeted to mutant p53. The 3-carbethoxy-4-phenyl-but-3-en-2-one is a novel compound that was designed as an anticancer agent targeted to mutant p53. Further evaluation of this compound was done by in silico examination employing Auto Dock Vina as molecular docking software. Molecular docking results denoted that 3-carbethoxy-4-phenyl-but-3-en-2-one had lower binding energy than methylene quinuclidinone (MQ). Visual inspection of the docking results denoted that 3-carbethoxy-4-phenyl-but-3-en-2-one docked in the binding pocket crystal structures of mutant p53 (2BIM, 2J1Y, and 2J21), forming a hydrogen bonding or hydrophobic interaction with Cys-124, and the distance between double bonds of α, β-unsaturated of 3-carbethoxy-4-phenyl-but-3-en-2-one with –SH group of Cys-124 were shorter than MQ. These results demonstrated that 3-carbethoxy-4-phenyl-but-3-en-2-one is a promising ligand to mutant p53 in many types of mutations and predicted to have better activity than MQ as a mutant p53 reactivator especially in cancers with mutation type Arg-273-His and Arg-245-Trp.

Ponicidin as a promising anticancer agent: Its biological and biopharmaceutical profile along with a molecular docking study

2019 ◽  
Vol 66 (3) ◽  
pp. 434-444 ◽  
Author(s):  
Muhammad Torequl Islam ◽  
Sajal Biswas ◽  
Rajat Bagchi ◽  
Md. Roich Khan ◽  
Abul Bashar Ripon Khalipha ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Anticancer Agent ◽  
Docking Study ◽  
Molecular Docking Study

scholarly journals Novel Structural Mechanism of Glutathione as a Potential Peptide Inhibitor to the Main Protease (Mpro): CoviD-19 Treatment, Molecular Docking and SAR Study

2020 ◽  
Author(s):  
abde lina ◽  
Khedidja BENAROUS ◽  
Mohamed Yousfi
Keyword(s):  
Molecular Docking ◽  
Pantothenic Acid ◽  
Vitamin B1 ◽  
Docking Study ◽  
Binding Pocket ◽  
Molecular Docking Study ◽  
Structural Mechanism ◽  
Discovery Studio ◽  
Main Protease ◽  
Sar Study

2019-nCoV Coronavirus spread all over the world and obliged one billion people in open confinement, no treatments or vaccine have been yet found against this pandemic. The Main Protease (M<sup>pro</sup>) is an attractive drug target, because it is the essential protein for the virus invasion. This study aims to test in silico the effect of five vitamins and a natural antioxidant against M<sup>pro</sup>, using molecular docking study, with Autodock Vina and Discovery Studio visualizer softwares. The used inhibitors were chosen based on their beneficial properties such as Tocopherol (vitamin E), Thiamine (vitamin B1), Pantothenic acid (vitamin B5), Pyridoxine (vitamin B6), Biotin (vitamin B7), and Glutathione (GSH), the best inhibitor pose was chosen based on the repetition ratio (RR) and the minimum affinity energy value (MEV). The results show that Glutathione is the best inhibitor model among the other tested vitamins in the active site of M<sup>pro</sup> with a RR value of 94% and MEV of - 5.5 kcal/mol, the compatibility of Glutathione structure inside the binding pocket as a tripeptide model found to be similar to the native ligand of M<sup>pro</sup>. Moreover, Thiamine, Biotin, and Tocopherol are saved as satisfied inhibitors to M<sup>pro</sup>, Pyridoxine was the weakest inhibitor. Depending on this result, we recommend the use of Glutathione and vitamin B family as a supportive strategy for the treatment of COVID-19.<br>

scholarly journals Novel Structural Mechanism of Glutathione as a Potential Peptide Inhibitor to the Main Protease (Mpro): CoviD-19 Treatment, Molecular Docking and SAR Study

2020 ◽  
Author(s):  
abde lina ◽  
Khedidja BENAROUS ◽  
Mohamed Yousfi
Keyword(s):  
Molecular Docking ◽  
Pantothenic Acid ◽  
Vitamin B1 ◽  
Docking Study ◽  
Binding Pocket ◽  
Molecular Docking Study ◽  
Structural Mechanism ◽  
Discovery Studio ◽  
Main Protease ◽  
Sar Study

2019-nCoV Coronavirus spread all over the world and obliged one billion people in open confinement, no treatments or vaccine have been yet found against this pandemic. The Main Protease (M<sup>pro</sup>) is an attractive drug target, because it is the essential protein for the virus invasion. This study aims to test in silico the effect of five vitamins and a natural antioxidant against M<sup>pro</sup>, using molecular docking study, with Autodock Vina and Discovery Studio visualizer softwares. The used inhibitors were chosen based on their beneficial properties such as Tocopherol (vitamin E), Thiamine (vitamin B1), Pantothenic acid (vitamin B5), Pyridoxine (vitamin B6), Biotin (vitamin B7), and Glutathione (GSH), the best inhibitor pose was chosen based on the repetition ratio (RR) and the minimum affinity energy value (MEV). The results show that Glutathione is the best inhibitor model among the other tested vitamins in the active site of M<sup>pro</sup> with a RR value of 94% and MEV of - 5.5 kcal/mol, the compatibility of Glutathione structure inside the binding pocket as a tripeptide model found to be similar to the native ligand of M<sup>pro</sup>. Moreover, Thiamine, Biotin, and Tocopherol are saved as satisfied inhibitors to M<sup>pro</sup>, Pyridoxine was the weakest inhibitor. Depending on this result, we recommend the use of Glutathione and vitamin B family as a supportive strategy for the treatment of COVID-19.<br>

scholarly journals Putative SARS-CoV-2 Mpro Inhibitors from an In-House Library of Natural and Nature-Inspired Products: A Virtual Screening and Molecular Docking Study

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3745 ◽  
Author(s):  
Stefania Mazzini ◽  
Loana Musso ◽  
Sabrina Dallavalle ◽  
Roberto Artali
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Chemical Space ◽  
Structural Diversity ◽  
Docking Study ◽  
Binding Pocket ◽  
Molecular Docking Study ◽  
Screening Experiments ◽  
Good Ability ◽  
Wide Range

A novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has been the cause of a recent global pandemic. The highly contagious nature of this life-threatening virus makes it imperative to find therapies to counteract its diffusion. The main protease (Mpro) of SARS-CoV-2 is a promising drug target due to its indispensable role in viral replication inside the host. Using a combined two-steps approach of virtual screening and molecular docking techniques, we have screened an in-house collection of small molecules, mainly composed of natural and nature-inspired compounds. The molecules were selected with high structural diversity to cover a wide range of chemical space into the enzyme pockets. Virtual screening experiments were performed using the blind docking mode of the AutoDock Vina software. Virtual screening allowed the selection of structurally heterogeneous compounds capable of interacting effectively with the enzymatic site of SARS-CoV-2 Mpro. The compounds showing the best interaction with the protein were re-scored by molecular docking as implemented in AutoDock, while the stability of the complexes was tested by molecular dynamics. The most promising candidates revealed a good ability to fit into the protein binding pocket and to reach the catalytic dyad. There is a high probability that at least one of the selected scaffolds could be promising for further research

scholarly journals Molecular Docking Study on the Binding Mode of Cardioselective Phenoxyaminopropanol Blocker into β-adrenergic Receptor Subtypes

2012 ◽  
Vol 59 (2) ◽  
pp. 44-53
Author(s):  
M. Polakovičová ◽  
R. Čižmáriková
Keyword(s):  
Molecular Docking ◽  
Adrenergic Receptor ◽  
Docking Study ◽  
Binding Pocket ◽  
Binding Mode ◽  
Receptor Subtypes ◽  
Molecular Docking Study ◽  
Subtype Selectivity ◽  
Extracellular Region ◽  
Selective Ligand

AbstractStructural understanding of subtype specific ligand-binding pocket variations and interactions of ligand with receptor may facilitate design of novel selective drugs. To gain insights into the subtype selectivity of β-blockers we performed flexible molecular docking study to analyze the interaction mode of cardioselective phenoxyaminopropanol blocker into the β1 and β2-adrenergic receptor. The binding site analysis reveals a strong identity between important amino acid residues and interactions with ligand in orthosteric catecholamine- binding pocket. The differences in the binding mode of selective ligand have been identified in the extracellular region of receptor subtypes.

scholarly journals Design, synthesis, in silico studies and biological evaluation of 5-((E)-4-((E)-(substituted aryl/alkyl)methyl)benzylidene)thiazolidine-2,4-dione derivatives

2020 ◽  
Author(s):  
Harsh Kumar ◽  
Aakash Deep ◽  
Rakesh Kumar Marwaha
Keyword(s):  
Molecular Docking ◽  
Radical Scavenging ◽  
Docking Study ◽  
Binding Pocket ◽  
Biological Evaluation ◽  
Dilution Method ◽  
Molecular Docking Study ◽  
Chemical Structures ◽  
Biological Potential ◽  
In Silico Studies

Abstract Background: Looking at the extensive range of biological potential of thiazolidine-2,4-dione (TZD) moiety, a new series of thiazolidine-2,4-dione analogues was synthesized. Different spectral techniques (1H-NMR, IR, MS etc.) were used to confirm the chemical structures of the synthesized analogues. These synthesized compounds were then screened for their antioxidant and antimicrobial potential.Results and discussion: The antimicrobial screening was carried out against selected strains of fungi and bacteria using serial tube dilution method. The antioxidant potential was assessed using stable 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging method. Further, the interaction between synthesized thiazolidine-2,4-dione compounds and DNA gyrase was explored using molecular docking studies. Various ADME parameters were also studied to evaluate the drug likeness of the synthesized compounds. Conclusion: In antimicrobial evaluation, the compounds 4, 9, 11, 12, 13, 15 and 16 displayed promising activity against selected strains of microbes. Antioxidant evaluation found compound 6 having IC50 = 9.18 μg/mL to be the most potent compound in the series. The molecular docking study revealed compounds 4 (dock score = -4.73) and 7 (dock score = -4.61) with decent docking score possess good interaction inside the ATP binding pocket and therefore can be used as lead structure for further optimizing into potent antimicrobial molecule.

EVALUATION OF IN-SILICO ANTICANCER POTENTIAL OF PYRETHROIDS: A COMPARATIVE MOLECULAR DOCKING STUDY

2015 ◽  
Author(s):  
Manik Ghosh ◽  
Kamal Kant ◽  
Anoop Kumar ◽  
Padma Behera ◽  
Naresh Rangra ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Molecular Docking Study

Myricetin Preferentially Binds to Interfacial Regions in Domains 1 – 3 to Inhibit Cholesterol-Dependent Cytolysins: A Molecular Docking Study

2020 ◽  
Author(s):  
Rafael Espiritu
Keyword(s):  
Molecular Docking ◽  
Structural Changes ◽  
Docking Study ◽  
Listeriolysin O ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Streptolysin O ◽  
Molecule Inhibitor ◽  
Human Cd59 ◽  
Anthrolysin O

<p>Cholesterol-dependent cytolysins (CDCs) are proteinaceous toxins secreted as monomers by some Gram-positive and Gram-negative bacteria that contribute to their pathogenicity. These toxins bind to either cholesterol or human CD59, leading to massive structural changes, toxin oligomerization, formation of very large pores, and ultimately cell death, making these proteins promising targets for inhibition. Myricetin, and its related flavonoids, have been previously identified as a candidate small molecule inhibitor of specific CDCs such as listeriolysin O (LLO) and suilysin (SLY), interfering with their oligomerization. In this work, molecular docking was performed to assess the interaction of myricetin with other CDCs whose crystal structures are already known. Results indicated that although myricetin bound to the hitherto identified cavity in domain 4 (D4), much more efficient and stable binding was obtained in sites along the interfacial regions of domains 1 – 3 (D1 – D3). This was common among the tested CDCs, which was primarily due to much more extensive stabilizing intermolecular interactions, as indicated by post-docking analysis. Specifically, myricetin bound to (1) the interface of the three domains in anthrolysin O (ALO), perfringolysin O (PFO), pneumolysin (PLY), SLY, and vaginolysin (VLY), (2) at/near the D1/D3 interface in LLO and streptolysin O (SLO), and (3) along the D2/D3 interface in intermedilysin (ILY). These findings provide theoretical basis on the possibility of using myricetin and its related compounds as a broad-spectrum inhibitor of CDCs to potentially address the diseases associated with these pathogens.</p>

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