scholarly journals Computational Evaluation of Bioactive Compounds from Colocasia affinis Schott as a Novel EGFR Inhibitor for Cancer Treatment

2021 ◽  
Vol 20 ◽  
pp. 117693512110492
Author(s):  
Toheeb A Balogun ◽  
Nureni Ipinloju ◽  
Olayemi T Abdullateef ◽  
Segun I Moses ◽  
Damilola A Omoboyowa ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cancer Treatment ◽  
Bioactive Compounds ◽  
Density Functional ◽  
Somatic Mutations ◽  
Chemical Reactivity ◽  
Transmembrane Protein ◽  
Egfr Inhibitors ◽  
Her Family ◽  
Lipinski’S Rule

Introduction: Epidermal growth factor receptor (EGFR) is a transmembrane protein that belongs to the ErbB/HER-family of tyrosine kinase receptors. Somatic mutations and overexpression of EGFR have been reported to play a vital role in cancer cell development and progression, including cell proliferation, differentiation, angiogenesis, apoptosis, and metastatic spread. Hence, EGFR is an important therapeutic target for the treatment of various types of epithelial cancers. Somatic mutations have led to resistance to clinically approved synthetic EGFR inhibitors. Furthermore, synthetic EGFR inhibitors have been associated with several side effects. Thus, there is a need to develop novel EGFR inhibitors with an acceptable biosafety profile and high efficacy. Methods: Herein, we employed structural bioinformatics and theoretical chemistry techniques via molecular docking, molecular mechanics generalized Born surface area (MM-GBSA) calculation, density functional theory analysis (DFT), and pharmacokinetic study to identify novel EGFR inhibitors. Results: The stringent molecular docking and MM-GBSA calculations identified MET 793, LYS 745, PHE 723, ASP 855, ARG 411, and THR 854 as principal amino acid residues for EGFR-ligands interactions. Furthermore, Colocasia affinis Schott compounds exhibited higher binding energy and more stable interactions than the reference compound (gefitinib). DFT analysis also ascertains better bioactivity and chemical reactivity of C. affinis Schott with favorable intramolecular charge transfer between electron-donor and electron acceptor groups. The pharmacokinetic profile of C. affinis Schott bioactive compounds satisfies Lipinski’s rule of five assessment. Conclusion: Collectively, C. affinis Schott compounds demonstrated higher inhibitory potentials against EGFR and better pharmacological properties when compared with gefitinib. C. affinis Schott compounds are therefore suggested as promising therapeutic EGFR inhibitors for cancer treatment.

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

Molecules ◽  
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).

scholarly journals Investigation of Some Antiviral N-Heterocycles as COVID 19 Drug: Molecular Docking and DFT Calculations

2020 ◽  
Vol 21 (11) ◽  
pp. 3922 ◽  
Author(s):  
Mohamed Hagar ◽  
Hoda A. Ahmed ◽  
Ghadah Aljohani ◽  
Omaima A. Alhaddad
Keyword(s):  
Dipole Moment ◽  
Molecular Docking ◽  
Dft Calculations ◽  
Binding Affinity ◽  
Electrostatic Potential ◽  
Density Functional ◽  
Molecular Electrostatic Potential ◽  
Hydrophobic Interactions ◽  
Chemical Reactivity ◽  
Main Protease

The novel coronavirus, COVID-19, caused by SARS-CoV-2, is a global health pandemic that started in December 2019. The effective drug target among coronaviruses is the main protease Mpro, because of its essential role in processing the polyproteins that are translated from the viral RNA. In this study, the bioactivity of some selected heterocyclic drugs named Favipiravir (1), Amodiaquine (2), 2′-Fluoro-2′-deoxycytidine (3), and Ribavirin (4) was evaluated as inhibitors and nucleotide analogues for COVID-19 using computational modeling strategies. The density functional theory (DFT) calculations were performed to estimate the thermal parameters, dipole moment, polarizability, and molecular electrostatic potential of the present drugs; additionally, Mulliken atomic charges of the drugs as well as the chemical reactivity descriptors were investigated. The nominated drugs were docked on SARS-CoV-2 main protease (PDB: 6LU7) to evaluate the binding affinity of these drugs. Besides, the computations data of DFT the docking simulation studies was predicted that the Amodiaquine (2) has the least binding energy (−7.77 Kcal/mol) and might serve as a good inhibitor to SARS-CoV-2 comparable with the approved medicines, hydroxychloroquine, and remdesivir which have binding affinity −6.06 and −4.96 Kcal/mol, respectively. The high binding affinity of 2 was attributed to the presence of three hydrogen bonds along with different hydrophobic interactions between the drug and the critical amino acids residues of the receptor. Finally, the estimated molecular electrostatic potential results by DFT were used to illustrate the molecular docking findings. The DFT calculations showed that drug 2 has the highest of lying HOMO, electrophilicity index, basicity, and dipole moment. All these parameters could share with different extent to significantly affect the binding affinity of these drugs with the active protein sites.

scholarly journals Molecular docking study of the phytol and its derivatives against COX-2 induced inflammation: A combined density functional study

2020 ◽  
pp. 1-5
Author(s):  
Muhammad Torequl Islam ◽  
Pranta Ray ◽  
Abul Bashar Ripon Khalipha ◽  
SM Hafiz Hassan ◽  
Md. Roich Khan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Density Functional ◽  
Chemical Reactivity ◽  
Docking Study ◽  
Functional Study ◽  
Molecular Docking Study ◽  
Study Results ◽  
Homo And Lumo ◽  
Cox 2

This study aimed to determine the activity of PYT and its derivatives against COX-2, including 5IKR protein induced inflammation by using the computational tools. PYT and its derivatives have been designed by utilizing density functional theory (DFT) and the performance of the drugs was also evaluated by molecular docking study. Results suggest that the NH2 derivative of PYT (D-NH2) showed binding energy -6.4 (Kcal/mol) with protein 5IKR of COX-2 compared to the main drug (D) that showed binding energy -5.1 (Kcal/mol) with the same protein. HOMO and LUMO energy values were also calculated to determine the chemical reactivity of all the modified drugs. Non-covalent interactions of PYT and its derivatives were essential in improving the performance. In conclusion, D-NH2 showed better preference in inhibiting to the protein 5IKR of COX-2 compared to other modified drugs and it can be claimed that D-NH2 will be the best conformer for COX-2 induced inflammation.

An In Silico Investigation of Potential EGFR Inhibitors for the Clinical Treatment of Colorectal Cancer

2019 ◽  
Vol 18 (27) ◽  
pp. 2355-2366 ◽  
Author(s):  
Manisha Majhi ◽  
Meer Asif Ali ◽  
Akanksha Limaye ◽  
Kritika Sinha ◽  
Praveena Bairagi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Docking ◽  
Growth Factor ◽  
Virtual Screening ◽  
Transforming Growth Factor ◽  
Transmembrane Protein ◽  
Protein A ◽  
Growth Factor Receptor ◽  
Transforming Growth Factor Β ◽  
Egfr Inhibitors

Colorectal cancer possesses the third highest diagnostic rate and is the second leading cause of cancer death in the USA as reported by NIH. Epidermal Growth Factor Receptor (EGFR), a transmembrane protein, participates in PLC gamma-1, RAS-RAF-MEK-MAPKs, phosphatidylinositol-3 kinase, Akt pathways and plays a key role in normal functioning of cell division, cell differentiation, apoptosis and migration. This protein is found to be overexpressed in more than 60% of the colorectal cancers. Overexpressed EGFR advances the tumorigenic properties through cell cycle dysregulation and activates signaling pathways linked to cancer such as WNT/β-catenin, transforming growth factor β (TGF-β) and phosphoinositide-3-kinase (PI3K). Inhibiting the overexpressed EGFR protein has been proposed for the treatment and many inhibitors have been reported suppressing the activity of EGFR. However, patients in malignant state of cancer show resistance to those inhibitors, which open a wide space to research for the discovery of novel inhibitors. The present study employed Molecular Docking and Virtual Screening to find novel inhibitors with high affinity against EGFR. Molecular docking of existing inhibitors resulted in the compound titled as BGB-283 (PubChem CID-89670174) having the highest score, which was subjected to similarity search to retrieve the drugs with similar structure. The virtual screening concluded a compound SCHEMBL18435602 (PubChem CID-126517400) which revealed a better affinity with the target protein. A comparative study of both the compounds showed equivalent pharmacokinetic properties. These identified drugs have a high potential to act as EGFR inhibitors and can show promising results in the research of colorectal cancer.

scholarly journals Molecular Docking Study on Several Benzoic Acid Derivatives against SARS-CoV-2

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5828
Author(s):  
Amalia Stefaniu ◽  
Lucia Pirvu ◽  
Bujor Albu ◽  
Lucia Pintilie
Keyword(s):  
Molecular Docking ◽  
Benzoic Acid ◽  
Density Functional ◽  
Chemical Reactivity ◽  
Principal Component ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Alkyl Gallates ◽  
Main Protease

Several derivatives of benzoic acid and semisynthetic alkyl gallates were investigated by an in silico approach to evaluate their potential antiviral activity against SARS-CoV-2 main protease. Molecular docking studies were used to predict their binding affinity and interactions with amino acids residues from the active binding site of SARS-CoV-2 main protease, compared to boceprevir. Deep structural insights and quantum chemical reactivity analysis according to Koopmans’ theorem, as a result of density functional theory (DFT) computations, are reported. Additionally, drug-likeness assessment in terms of Lipinski’s and Weber’s rules for pharmaceutical candidates, is provided. The outcomes of docking and key molecular descriptors and properties were forward analyzed by the statistical approach of principal component analysis (PCA) to identify the degree of their correlation. The obtained results suggest two promising candidates for future drug development to fight against the coronavirus infection.

scholarly journals Density Functional Theory, Chemical Reactivity, Pharmacological Potential and Molecular Docking of Dihydrothiouracil-Indenopyridopyrimidines with Human-DNA Topoisomerase II

2020 ◽  
Vol 21 (4) ◽  
pp. 1253 ◽  
Author(s):  
Mohamed E. Elshakre ◽  
Mahmoud A. Noamaan ◽  
Hussein Moustafa ◽  
Haider Butt
Keyword(s):  
Density Functional Theory ◽  
Molecular Docking ◽  
Density Functional ◽  
Topoisomerase Ii ◽  
Chemical Reactivity ◽  
Antitumor Drug ◽  
Binding Energies ◽  
Basis Sets ◽  
Chemical Hardness ◽  
Functional Theory

In this work, three computational methods (Hatree-Fock (HF), Møller–Plesset 2 (MP2), and Density Functional Theory (DFT)) using a variety of basis sets are used to determine the atomic and molecular properties of dihydrothiouracil-based indenopyridopyrimidine (TUDHIPP) derivatives. Reactivity descriptors of this system, including chemical potential (µ), chemical hardness (η), electrophilicity (ω), condensed Fukui function and dual descriptors are calculated at B3LYP/6-311++ G (d,p) to identify reactivity changes of these molecules in both gas and aqueous phases. We determined the molecular electrostatic surface potential (MESP) to determine the most active site in these molecules. Molecular docking study of TUDHIPP with topoisomerase II α and β is performed, predicting binding sites and binding energies with amino acids of both proteins. Docking studies of TUDHIPP versus etoposide suggest their potential as antitumor candidates. We have applied Lipinski, Veber’s rules and analysis of the Golden triangle and structure activity/property relationship for a series of TUDHIPP derivatives indicate that the proposed compounds exhibit good oral bioavailability. The comparison of the drug likeness descriptors of TUDHIPP with those of etoposide, which is known to be an antitumor drug, indicates that TUDHIPP can be considered as an antitumor drug. The overall study indicates that TUDHIPP has comparable and even better descriptors than etoposide proposing that it can be as effective antitumor drug, especially 2H, 6H and 7H compounds.

scholarly journals The Oxidative Process of Acarbose, Maysin, and Luteolin with Maltase-Glucoamylase: Molecular Docking and Molecular Dynamics Study

2021 ◽  
Vol 11 (9) ◽  
pp. 4067
Author(s):  
Linda-Lucila Landeros-Martínez ◽  
Néstor Gutiérrez-Méndez ◽  
Juan Pedro Palomares-Báez ◽  
Nora-Aydeé Sánchez-Bojorge ◽  
Juan Pablo Flores-De los Ríos ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Molecular Docking ◽  
Active Site ◽  
Density Functional ◽  
Chemical Reactivity ◽  
Basis Set ◽  
Electronic Charge ◽  
Chemical Hardness ◽  
Oxidative Process

Type 2 diabetes mellitus has been classified as the epidemic of the XXI century, making it a global health challenge. Currently, the commonly used treatment for this disease is acarbose, however, the high cost of this medicine has motivated the search for new alternatives. In this work, the maysin, a characteristic flavonoid from maize inflorescences, and its aglycon version, luteolin, are proposed as acarbose substitutes. For this, a theoretical comparative analysis was conducted on the molecular interactions of acarbose, maysin, and luteolin with human maltase-glucoamylase (NtMGAM), as well as their oxidative process. The binding energies in the active site of NtMGAM with acarbose, maysin, and luteolin molecules were predicted using a molecular docking approach applying the Lamarckian genetic algorithm method. Theoretical chemical reactivity parameters such as chemical hardness (η) and chemical potential (µ) of the acarbose, maysin, and luteolin molecules, as well as of the amino acids involved in the active site, were calculated using the electronic structure method called Density Functional Theory (DFT), employing the M06 meta-GGA functional in combination with the 6-31G(d) basis set. Furthermore, a possible oxidative process has been proposed from quantum-chemical calculations of the electronic charge transfer values (ΔN), between the amino acids of the active site and the acarbose, maysin, and luteolin. Molecular docking predictions were complemented with molecular dynamics simulations. Hence, it was demonstrated that the solvation of the protein affects the affinity order between NtMGAM and ligands.

scholarly journals Analysis of the Molecular Interactions between Cytochromes P450 3A4 and 1A2 and Aflatoxins: A Docking Study

2019 ◽  
Vol 9 (12) ◽  
pp. 2467 ◽  
Author(s):  
Isui Abril García-Montoya ◽  
Norma Rosario Flores-Holguín ◽  
Linda-Lucila Landeros-Martínez ◽  
Mónica Alvarado-González ◽  
Quintín Rascón-Cruz ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Amino Acids ◽  
Molecular Docking ◽  
Charge Transfer ◽  
Active Site ◽  
Density Functional ◽  
Chemical Reactivity ◽  
Cytochromes P450 ◽  
Docking Analysis ◽  
Molecular Docking Analysis

Mycotoxins known as aflatoxins (AF) are produced as a secondary metabolite by some species of Aspergillus fungi. They are considered carcinogenic, hepatotoxic, teratogenic, and mutagenic. In this study, the molecular structure, chemical reactivity, and charge transfer values of AFB1, B2, G1, and G2 were analyzed using density functional theory. Different methodologies—B3LYP/6-311G(d,p) and M06-2X/6-311G(d,p)—were applied for geometrical calculations. Chemical reactivity parameters were used in the calculation of charge transfer values during the interaction between protein and ligand. The binding energy, the electrostatic interactions, and the amino acids of the active site were determined by molecular docking analysis between AF and cytochromes P450 (3A4 and 1A2), employing different PDB files (CYP3A4:1TQN, 2V0M, 4NY4 and 1W0E, and CYP1A2:2HI4). Molecular docking analysis indicated that the central rings of the AF are involved in the interaction with the HEM group of the active site. The differences in the molecular structure of the AF affect their position regarding the HEM group. The resulting configurations presented considerable variation in the amino acids and the position of the coupling. The charge transfer values showed that there is oxidative damage inside the active site and that the HEM group is responsible for the main charge transferences.

Exploration of Luteolin as Potential Anti-COVID19 agent: Molecular Docking, Molecular Dynamic Simulation, ADMET and DFT analysis

2021 ◽  
Vol 19 ◽  
Author(s):  
Waseem Ahmad Ansari ◽  
Tanveer Ahamad ◽  
Mohsin Ali Khan ◽  
Zaw Ali Khan ◽  
Mohammad Faheem Khan
Keyword(s):  
Molecular Docking ◽  
Molecular Dynamic ◽  
Molecular Modelling ◽  
Density Functional ◽  
Chemical Reactivity ◽  
Antiviral Agent ◽  
Receptor Protein ◽  
Human Consumption ◽  
Dft Methods ◽  
Protein Receptors

Background: Recently, coronavirus disease-2019 (COVID-19) has become a pandemic disease of the respiratory tract having mild to severe symptoms of pneumonia. No clinical antiviral agent is available so far, however, several repurposing drugs and vaccine are being given to individuals or in clinical trials against SARS-CoV-2 Objective: The aim of this study is to uncover the potential effects of Luteolin (Lut) as an inhibitor of SARS-CoV2 encoded proteins via utilizing computational tools Method: Molecular modelling to unfold the anti-SARS-CoV2 potential of Lut along with reference drugs namely remdesivir and nafamostat was performed by the use of molecular docking, molecular dynamic (MD) simulation, absorption, distribution, metabolism, excretion, toxicity (ADMET) and density functional theory (DFT) methods against the five different SARS-CoV-2 encoded key proteins and one human receptor protein. The chemical reactivity of Luteolin is done through prediction of HOMO-LUMO gap energy and other chemical descriptors analysis Results: In the present study, Lut binds effectively in the binding pockets of spike glycoprotein (6VSB), ADP phosphatase of NSP3 (6W02), and RNA dependent RNA polymerase (7AAP) protein receptors with significant values of docking scores -7.00, -7.25, and -6.46 respectively as compared to reference drugs remdesivir and nafamostat. Conclusion:: Thus, Lut can act as therapeutic agent and is orally safe for human consumption as predicted by molecular modelling against SARS-CoV-2 in the treatment of COVID-19

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