Molecular docking and QSAR theoretical model for prediction of phthalazinone derivatives as new class of potent dengue virus inhibitors

Abstract Background Dengue fever is a key public health unease in various tropical and sub-tropical regions. The improvement of existing agents that can inhibit the dengue virus is therefore of utmost importance. In this work, the QSAR study was carried out on 25 molecules of phthalazinone derivatives which have been reported to possess excellent dengue virus inhibitory activity. Density functional computational technique was used in the optimisation of the molecules with the basis set at theory level (B3LYP, 6-31G*) respectively. The multiple linear regression (MLR) model was built using genetic function approximation (GFA) in the material studio software package. Also, in this study, molecular docking simulation was carried between dengue virus serotype 2 protease (PDB CODE: 6mol) and some selected phthalazinone derivatives (compounds 1, 2, 7, 11, and 21). Results The model was robust as evidenced by validation and robustness statistical parameter which include predicted R2pred., adjusted R2adj., cross-validated Q2 and R2 regression coefficient, etc (R2pred. = 0.71922, R2adj. = 0.939699, Q2CV = 0.905909, R2 = 0.955567) respectively. The molecular docking studies conducted in this study have outlined the binding affinities of the selected compounds (1, 2, 7 11, and 21) which are all in good correlation with their respective pIC50 values. The free binding affinities of the selected compounds were found to be (− 8.7, − 8.8, − 8.7, − 8.3, and − 8.9 kcal/mol) respectively, compound 21 with the binding affinity of − 8.9 kcal/mol had the best binding free energy with the protease relative to other compounds under consideration. Conclusion The MLR-GFA model study alongside with the molecular docking analysis has essentially provided a valuable and in-depth understanding as well as knowledge for the development of novel chemical compounds with enhanced inhibitory potential against the dengue virus serotype 2 (DNV-2). Hence, the developed model can be applicable in predicting the anti-dengue activity of a new set of chemical compounds that fall within its applicability domain.

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Molecular docking study of Lens culinaris L. phytochemicals to NS3-NS2B protease of dengue virus serotype 2

German Journal of Microbiology - Special Issue: Existence Battle: Viruses vs. Creatures ◽

10.51585/gjm.2021.0005 ◽

2021 ◽

Vol 1 (1) ◽

pp. 26-37

Keyword(s):

Molecular Docking ◽

Binding Energy ◽

Dengue Virus ◽

Binding Affinity ◽

Lens Culinaris ◽

Binding Affinities ◽

High Binding ◽

Virus Serotype ◽

Dengue Virus Serotype 2 ◽

High Binding Affinity

Forty-three phytochemicals present in Lens culinaris were evaluated through in-silico molecular docking studies for their binding affinities to the NS2B-NS3 activator-protease complex of dengue virus serotype 2 (DENV-2). Among the various compounds tested, flavonoids (flavanols,favonols, proanthocyanidins, flavanones, flavones, and anthocyanins) demonstrated high binding affinities for the protease complex. Eriodictyol-7-O-rutinoside showed the least predicted binding energy at -9.1 kcal/mol followed by luteolin-7-O-glucoside at -8.8 kcal/mol. Glycosidic linkages appeared to enhance the binding affinities of flavonoids, aldohexoses being more potent than aldopentoses. Besides flavonoids, other classes of compounds demonstrating high binding affinities for the protease were carotenoids, phytosterols, and polyphenolic compounds like resveratrol and trans-resveratrol 3-O-b-glucoside (piceid), the latter showing predicted binding energy of -8.5 kcal/mol versus predicted binding energy of -7.2 kcal/mol for resveratrol. The 2D interactions of four high binding affinity compounds like eriodictyol, eriodictyol-7-O-rutinoside, catechin gallate, and luteolin-7-O-glucoside showed that all four compounds bound to the active site of the NS3 protease and not to the activator NS2B. Lys74 of NS3 was the common amino acid interacting with all four phytochemicals. Analysis of physicochemical properties of the compounds (Lipinski's Rule of 5) showed that the high binding affinity compounds have less than two violations, indicating that they can serve as useful lead compounds or as dengue virus serotype 2 therapeutics.

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Virtual screening of commercial cyclic peptides as NS2B-NS3 protease inhibitor of dengue virus serotype 2 through molecular docking simulation

IOP Conference Series Materials Science and Engineering ◽

10.1088/1757-899x/188/1/012017 ◽

2017 ◽

Vol 188 ◽

pp. 012017 ◽

Cited By ~ 2

Author(s):

M A F Nasution ◽

R N Aini ◽

U S F Tambunan

Keyword(s):

Molecular Docking ◽

Virtual Screening ◽

Dengue Virus ◽

Protease Inhibitor ◽

Cyclic Peptides ◽

Docking Simulation ◽

Molecular Docking Simulation ◽

Virus Serotype ◽

Ns3 Protease ◽

Dengue Virus Serotype 2

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Density Functional Theory and Molecular Docking Investigations of the Chemical and Antibacterial Activities for 1-(4-Hydroxyphenyl)-3-phenylprop-2-en-1-one

Molecules ◽

10.3390/molecules26123631 ◽

2021 ◽

Vol 26 (12) ◽

pp. 3631

Author(s):

Ahmed M. Deghady ◽

Rageh K. Hussein ◽

Abdulrahman G. Alhamzani ◽

Abeer Mera

Keyword(s):

Density Functional Theory ◽

Antibacterial Activity ◽

Molecular Docking ◽

Carbonyl Group ◽

Active Sites ◽

Density Functional ◽

Chemical Reactivity ◽

Basis Set ◽

Molecular Docking Study ◽

Functional Theory

The present investigation informs a descriptive study of 1-(4-Hydroxyphenyl) -3-phenylprop-2-en-1-one compound, by using density functional theory at B3LYP method with 6-311G** basis set. The oxygen atoms and π-system revealed a high chemical reactivity for the title compound as electron donor spots and active sites for an electrophilic attack. Quantum chemical parameters such as hardness (η), softness (S), electronegativity (χ), and electrophilicity (ω) were yielded as descriptors for the molecule’s chemical behavior. The optimized molecular structure was obtained, and the experimental data were matched with geometrical analysis values describing the molecule’s stable structure. The computed FT-IR and Raman vibrational frequencies were in good agreement with those observed experimentally. In a molecular docking study, the inhibitory potential of the studied molecule was evaluated against the penicillin-binding proteins of Staphylococcus aureus bacteria. The carbonyl group in the molecule was shown to play a significant role in antibacterial activity, four bonds were formed by the carbonyl group with the key protein of the bacteria (three favorable hydrogen bonds plus one van der Waals bond) out of six interactions. The strong antibacterial activity was also indicated by the calculated high binding energy (−7.40 kcal/mol).

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Dengue Virus Serotype-2 Interferes with the Formation of Neutrophil Extracellular Traps

Intervirology ◽

10.1159/000440723 ◽

2015 ◽

Vol 58 (4) ◽

pp. 250-259 ◽

Cited By ~ 13

Author(s):

Maria Maximina B. Moreno-Altamirano ◽

Oscar Rodríguez-Espinosa ◽

Oscar Rojas-Espinosa ◽

Bernardo Pliego-Rivero ◽

Francisco J. Sánchez-García

Keyword(s):

Dengue Virus ◽

Neutrophil Extracellular Traps ◽

Extracellular Traps ◽

Virus Serotype ◽

Dengue Virus Serotype 2

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Synthesis, Quantum Chemical Calculations, Molecular Docking and Studying the Effect of High Energetic Gamma Irradiation on Cu(I, II), Zn(II) and Cd(II) Complexes with their Antibacterial Activity.

10.21203/rs.3.rs-836470/v1 ◽

2021 ◽

Author(s):

Hussein Elganzory

Keyword(s):

Molecular Docking ◽

Gamma Irradiation ◽

Density Functional ◽

Topoisomerase Ii ◽

Gamma Ray ◽

Inhibitory Effect ◽

Molar Conductance ◽

Basis Set ◽

Conformational Structure ◽

Before And After

Abstract New complexes of Cu(I,II), Zn(II) and Cd(II) of thiosemicarbazide ligand 1-(p-(methylanilinocetyl-4-phenyl-thiosemicarbazide)(H2LB) have been prepared and characterized by 1HNMR, Mass spectra, FT-IR, elemental analyses, molar conductance, UV-visible spectra, magnetic susceptibility measurements, thermogravimetric analysis (TGA/DTG) and X-ray diffraction pattern before and after irradiation. The results confirmed that gamma ray enhanced the stability of irradiated compounds as compared to non-irradiated compounds. XRD patterns proved that increasing the crystallinity of the samples and the particles in nano range after gamma irradiation. The obtained data indicated that the Cu(I) and Cd(II) ions coordinated to the ligand through the (C = O), N(2)H and (C = S), the ligand behaves as neutral tridentate. While in complexes Cu(II) and Zn(II)complexes (B2 and B3) the ligand behave as neutral tetradentate and coordination take place via (C = O) and two N(2)H. These studies revealed that, two kinds of stereochemical geometries; Cu(II) and Zn(II) complexes were predicted to be octahedral, Cu(I) and Cd(II)complexes were found to be tetrahedral. The theoretical conformational structure analyses were performed using density functional theory for ligand and complexes at B3LYP functional with 6-31G(++)d,p basis set for ligand and LANL2DZ basis set for complexes. The ligand and its metal complexes have been tested for their inhibitory effect on the growth of bacteria against gram-positive (Streptococcus pyogenes) and gram-negative (Escherichia coli). Results suggested that in case of 1µg/ml and 5µg/ml for Cu(II) and Zn(II) complexes have higher activity than other complexes. The chelation could facilitate the ability to cross the cell membrane of E. coli and can be explained by Tweedy’s chelation theory. Molecular docking investigation proved that; the Zn(II) complex had interesting interactions with active site amino acids of topoisomerase II DNA gyrase enzymes (code: 2XCT).

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