New flavone-based arylamides as potential V600E-BRAF inhibitors: Molecular docking, DFT, and pharmacokinetic properties

Umar, Abdullahi Bello; Uzairu, Adamu

doi:10.1016/j.jtumed.2023.02.010

Cited by 6 publications

(10 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, the reactivity order of these ligands decreases accordingly as the energy gap (∆E) increases with ligand C4 (∆E = 3.28 eV) having the highest reactivity. Chemical hardness (η) and softness (σ) are critical descriptors for the behavior of a molecule in a chemical reaction (Umar and Uzairu, 2022). Whereas hard molecules have a high resistance to changing their electronic distribution during a reaction, soft molecules have a low resistance to changing their electronic distribution during a reaction (Umar and Uzairu, 2022).…”

Section: Dft Computationsmentioning

confidence: 99%

“…Electrophilicity index (ω) which is an indicator of the electrophilic nature of a chemical specie measures the tendency of a molecule to accept electron (Umar and Uzairu, 2022). The ranking of organic molecules based on electrophilicity is as follows; molecules with ω < 0.8 eV are weak electrophiles, molecules with 0.8 eV < ω < 1.5 eV are moderate electrophiles while molecules with ω > 1.5 eV are strong electrophiles (Umar and Uzairu, 2022). The electrophilicity values of the five selected ligands in this series therefore shows that the compounds are strong electrophiles since their electrophilicity values ranges between 3.544 eV (ligand C3) and 5.876 eV (ligand C4).…”

Section: Ligandmentioning

confidence: 99%

“…The blue and red colors of the diagrams in figure 4 shows the positive and negative values of the orbitals respectively. Conventionally also, the blue region represents the maximum value of the HOMO, and the red region represents the minimum value (Umar and Uzairu, 2022).…”

Section: Ligandmentioning

confidence: 99%

“…The chemical potential (μ) as presented in table 3, shows negative values for all the studied ligands, indicating good stability with the receptor. Electrophilicity index (ω) which is an indicator of the electrophilic nature of a chemical specie measures the tendency of a molecule to accept electron (Umar and Uzairu, 2022). The ranking of organic molecules based on electrophilicity is as follows; molecules with ω < 0.8 eV are weak electrophiles, molecules with 0.8 eV < ω < 1.5 eV are moderate electrophiles while molecules with ω > 1.5 eV are strong electrophiles (Umar and Uzairu, 2022).…”

Section: Ligandmentioning

confidence: 99%

“…Molecular docking, which is an excellent computational technique used for filtering series of chemical libraries to identify potential chemicals that could be used to find the binding capacity for a specific target, is widely used to select the best alignment of drug candidates in the active site of a protein and predict their affinity . Other authors have also extensively used molecular docking simulation to investigate the biological activity of various chemical structures , , (Umar and Uzairu, 2022) and (Abdullahi et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

In-silico Investigation by Molecular Docking, DFT and Pharmacokinetic Studies of Some Synthesized 1,8-Naphthyridine Derivatives as Prospective Anti-Breast Cancer Agents

Magit,

Umar,

Magit

2023

Preprint

View full text Add to dashboard Cite

Cancer, which has been identified as the second leading causes of health-related mortalities worldwide, is a disease in which some cells of the human body grow uncontrollably and spread to other parts of the body. The resistance of cancer (especially breast cancer) cells to known treatments as well as the adverse side effects associated with current anti-breast cancer drugs necessitates the discovery of novel and potent drug candidates. In this study, in-silico approaches such as DFT studies, Molecular Docking simulation and pharmacokinetic property predictions were used to examine the potency of seventeen (17) previously synthesized novel derivatives of 1,8-naphthyridine as potent anti-breast cancer agents using the Tamoxifen Standard drug (an FDA approved drug for the treatment of breast cancer) as reference. From the molecular docking studies, most of the compounds were found to have better binding energy to the human estrogen receptor (PDB ID: 1ERR) than the control drug (Tamoxifen, Mol. Dock score = −137.807, Re-rank score = −106.527 Kcalmol-1). Compounds C3 and C13 (with Mol. Dock scores -147.054 and -147.819 Kcalmol-1 respectively), which had superior docking scores than the standard drug, were found to be stable based of DFT studies. The predicted drug-likeness and pharmacokinetics properties of these two compounds were also found to be within the acceptable optimal requirements for drug development. Based on the results therefore, compounds C3 and C13 are proposed as potent anti-breast cancer drug candidates with better anti-breast Cancer capacity than the tamoxifen standard drug.

show abstract

Section: Dft Computationsmentioning

confidence: 99%

Section: Ligandmentioning

confidence: 99%

Section: Ligandmentioning

confidence: 99%

Section: Ligandmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

In-silico Investigation by Molecular Docking, DFT and Pharmacokinetic Studies of Some Synthesized 1,8-Naphthyridine Derivatives as Prospective Anti-Breast Cancer Agents

Magit,

Umar,

Magit

2023

Preprint

View full text Add to dashboard Cite

show abstract

Investigation into the Quantitative Structure‐Biotoxicity Relationship of Antibiotics and their Estrogenic Receptor Disruption Effects

Zhu,

Chen,

Wang

et al. 2024

Chemistry & Biodiversity

View full text Add to dashboard Cite

In light of antibiotics being classified as environmental hormone‐like compounds, their interference with the endocrine system has significantly impacted human health and ecological environments. This study employed Gaussian09 software's Density Functional Theory (DFT) to structurally optimize and perform frequency calculations on 23 representative antibiotic molecules, aiming to obtain microscopic quantum mechanical structural parameters.Physicochemical property parameters were acquired through the RDKit database in the ChemDes platform. Through multiple linear regression analysis, the primary factors affecting antibiotic biotoxicity (pLD50) were identified, leading to the establishment of a QSAR model. The predictive capability of the model was analyzed using leave‐one‐out cross‐validation, and molecular docking was used to investigate the binding mode and mechanism of action between estrogen receptors (ER) and antibiotics. Research outcomes indicate that the established QSAR model C has regression coefficients R2 and leave‐one‐out cross‐validation coefficients Q2 of 0.92474 and 0.74913, respectively, demonstrating good stability and predictive power. Analysis through molecular surface electrostatic potential, frontier molecular orbitals, molecular docking, and molecular dynamics revealed that the potential estrogenic disrupting effects are primarily due to hydrogen bonds and hydrophobic interactions between antibiotics and estrogen receptors. This provides a valuable exploration for identifying and screening PPCPs with potential estrogenic disrupting effects.

show abstract

Ursolic acid interaction with transcription factors BRAF, V600E, and V600K: a computational approach towards new potential melanoma treatments

Aguilera-Durán,

Hernández-Castro,

Loera-García

et al. 2024

J Mol Model

View full text Add to dashboard Cite

New flavone-based arylamides as potential V600E-BRAF inhibitors: Molecular docking, DFT, and pharmacokinetic properties

Cited by 6 publications

References 51 publications

In-silico Investigation by Molecular Docking, DFT and Pharmacokinetic Studies of Some Synthesized 1,8-Naphthyridine Derivatives as Prospective Anti-Breast Cancer Agents

In-silico Investigation by Molecular Docking, DFT and Pharmacokinetic Studies of Some Synthesized 1,8-Naphthyridine Derivatives as Prospective Anti-Breast Cancer Agents

Investigation into the Quantitative Structure‐Biotoxicity Relationship of Antibiotics and their Estrogenic Receptor Disruption Effects

Ursolic acid interaction with transcription factors BRAF, V600E, and V600K: a computational approach towards new potential melanoma treatments

Contact Info

Product

Resources

About