Theoretical Study of N-Methyl-3-Phenyl-3-(4-(Trifluoromethyl) Phenoxy) Propan as a Drug and Its Five Derivatives

AL-Makhzumi, Qabas M. Abdul Hussein; Abdullah, Hussein I.; Alani, Ramzie

doi:10.4236/jbm.2018.68007

Cited by 9 publications

(7 citation statements)

References 15 publications

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“…The HOMO energy describes the electron-donating ability; higher values of E HOMO indicate a better tendency of the molecule to donate electron. 38 The E LUMO determines the power of a molecule to accept an electron, lower value of E LUMO of a molecule increases the probability of accepting electrons. Therefore, higher values of E HOMO and lower values of E LUMO are responsible for the low stability and high reactivity of a molecule.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2021

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“…E LUMO describes the electron-donating ability of a molecule while E LUMO explains the electron-accepting ability of a molecule. High E HOMO and low E LUMO values signify the great potential of a molecule to donate and accept electrons readily [30][31][32]. From Table 2, it was observed that lumateperone had a higher value of E HOMO (-4.47 eV) than other compounds.…”

Section: Quantum Chemical Calculationsmentioning

confidence: 97%

“…The FMOs locate the area of chemical bonds that are chemically reactive. This has been used for describing the chemical reactivity and stability of small molecules [30][31][32]. Highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) are the two most important molecular orbitals in a molecule.…”

Section: Quantum Chemical Calculationsmentioning

confidence: 99%

Discovery of Small Molecule PARKIN Activator as Therapeutics for PD: An in-silico Repurposing Approach

Ibrahim

Ipinloju

Muhammad

et al. 2022

Preprint

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Background Although there is presently no cure for Parkinson's disease (PD), the available therapies are only able to lessen symptoms and preserve the quality of life. Around 10 million people globally had PD as of 2020. The widely used standard drug has recently been revealed to have several negative effects. Additionally, there is a dearth of innovative compounds entering the market as a result of subpar ADMET characteristics. Drug repurposing provides a chance to reenergize the sluggish drug discovery process by identifying new applications for already-approved medications. As this strategy offers a practical way to speed up the process of developing alternative medications for PD. This study used a computer-aided technique to select therapeutic agent(s) from FDA-approved neuropsychiatric/psychotic drugs that can be adopted in the treatment of Parkinson's disease. Method In the current work, a computational approach via molecular docking, density functional theory (DFT), and pharmacokinetics were used to identify possible (anti)neuropsychiatric/psychotic medications for the treatment of PD. By using molecular docking, about eight (anti)neuropsychiatric/psychotic medications were tested against PARKIN, a key protein in PD Result Based on the docking score, the best ligand in the trial was determined. The top hits were compared to the reference ligand levodopa (L-DOPA). A large proportion of the drugs displayed binding affinity that was relatively higher than L-DOPA. Also, DFT analysis confirms the ligand-receptor interactions and the molecular charges transfer. All the compounds were found to obey Lipinski's rule with acceptable pharmacokinetic properties. Conclusion The current study has revealed the effectiveness of antineuropsychiatric/antipsychotic drugs against PARKIN in the treatment of PD and lumateperone was revealed to be the most promising candidate interacting with PARKIN.

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“…[98,99] An increase in energy gap correlate with a decrease in a compound's reactivity and vice versa thus high energy gap indicates less susceptibility to react with other compounds. [98] Among the flavonoids, ST024026 had the least energy gap as shown in Table 4, suggesting it is more reactive than the other flavonoids. Compared to STM2457, the flavonoids exhibited relatively higher energy gap highlighting lower reactivity compared to STM2457.…”

Section: Chemical Reactivity Descriptors From Dft Calculationsmentioning

confidence: 99%

Leveraging Flavonoids as Potential Inhibitors of METTL3 in Combating Cancer: A Combined Structure‐Based Drug Design and DFT Approach

Abo‐Dya,

Issahaku

2023

ChemistrySelect

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Methyltransferase‐like 3 (METTL3) serves as a primary catalytic enzyme within the N6‐ methyladenosine (m6 A) methyltransferase system, playing a crucial role in various biological processes. However, its involvement in the pathogenesis of several cancers, have been well documented. The pursuit of small molecule inhibitors to counteract the cancer‐promoting effects of METTL3 has gained considerable momentum; however, no approved drugs are available. In this study, we employed computational techniques, including structure‐based virtual screening, consensus molecular docking, Density Function Theory calculations and MMPBSA energy profiling to identify potential METTL3 inhibitors from flavonoids. ST024026, ST99039 and ST4135876 were identified as promising candidates for METTL3 inhibition, as indicated by their favorable docking scores and robust energy profiles. Notably, their binding interactions were characterized by strong hydrogen bonds and hydrophobic contacts, ensuring high stability within the METTL3 binding site. Furthermore, these compounds exhibited favorable physicochemical properties and ADME characteristics, coupled with minimal toxicity. Notably, their binding induced conformational changes in the protein, underscoring their potential as METLL3 inhibitors. These findings highlight the selected flavonoids as potential novel entry inhibitors subject to modifications and optimizations. To advance this line of research, additional biochemical testing and experimental validation are warranted to facilitate the development of highly selective and effective METTL3 inhibitors.

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Theoretical Study of N-Methyl-3-Phenyl-3-(4-(Trifluoromethyl) Phenoxy) Propan as a Drug and Its Five Derivatives

Cited by 9 publications

References 15 publications

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

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

Discovery of Small Molecule PARKIN Activator as Therapeutics for PD: An in-silico Repurposing Approach

Leveraging Flavonoids as Potential Inhibitors of METTL3 in Combating Cancer: A Combined Structure‐Based Drug Design and DFT Approach

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