<i>In Silico</i> Studies of Piperidine Derivatives as Protein Kinase B Inhibitors
through 3D-QSAR, Molecular Docking and Molecular Dynamics Simulation

Liu, Sisi; Li, Yaxin; Wang, Jin; Xue, Rui; Tian, Haobo; Li, Chenshuo; Guo, Chunyan

doi:10.2174/1570180818666211207105516

Cited by 4 publications

(2 citation statements)

References 41 publications

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“…Charges were neutralized by adding counterions (Na + or Cl – ). Then, the system was relaxed through an energy minimization process using the Desmond default relaxation protocol . After that, a production MD simulation was performed under NPT ensemble class.…”

Section: Methodsmentioning

confidence: 99%

“…Then, the system was relaxed through an energy minimization process using the Desmond default relaxation protocol. 44 After that, a production MD simulation was performed under NPT ensemble class. Throughout the simulation process, the temperature was fixed at 300 K and the pressure was set at 1.01325 bar using a Nose−Hoover thermostat and Martyna−Tobias−Klein barostat, respectively.…”

Section: E)-n-(4-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-56-dihydro-...mentioning

confidence: 99%

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Discovery of Novel 5,6-Dihydro-4H-pyrido[2,3,4-de]quinazoline Irreversible Inhibitors Targeting Both Wild-Type and A775_G776insYVMA Mutated HER2 Kinases

Yang,

Li,

et al. 2024

J. Med. Chem.

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HER2 mutations were seen in 4% of non-small-cell lung cancer (NSCLC) patients. Most of these mutations (90%) occur as an insertion mutation within the exon 20 frame, leading to the downstream activation of the PI3K-AKT and RAS/MAPK pathways. However, no targeted therapies have yet been approved worldwide. Here a novel series of highly potent HER2 inhibitors with a pyrido[2,3,4-de]quinazoline core were designed and developed. The derivatives with the pyrido[2,3,4-de]quinazoline core displayed superior efficacy of antiproliferation in BaF3 cells harboring HER2insYVMA mutation compared with afatinib and neratinib. Rat studies showed that 8a and 9a with the newly developed core have good pharmacokinetic properties with an oral bioavailability of 41.7 and 42.0%, respectively. Oral administration of 4a and 10e (30 mg/kg, QD) displayed significant antitumor efficacy in an in vivo xenograft model. We proposed promising strategies for the development of HER2insYVMA mutant inhibitors in this study.

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Section: Methodsmentioning

confidence: 99%

Section: E)-n-(4-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-56-dihydro-...mentioning

confidence: 99%

Discovery of Novel 5,6-Dihydro-4H-pyrido[2,3,4-de]quinazoline Irreversible Inhibitors Targeting Both Wild-Type and A775_G776insYVMA Mutated HER2 Kinases

Yang,

Li,

et al. 2024

J. Med. Chem.

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Design, synthesis and biological evaluation of novel diaminopyrimidine derivatives as covalent fibroblast growth factor receptor 4 inhibitors

Wei¹,

Li²,

Peng³

et al. 2023

Results in Chemistry

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In silico Exploration of the Potential Inhibitory Activity of Novel Compounds Against Candida albicans N-myristoyltransferase

Hussain

Verma

2024

LDDD

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Background: Candida albicans is a fungal species associated with opportunistic fungal infectious agents in human populations, especially in immunocompromised patients such as transplant patients, HIV-positive patients, chemotherapy patients, and low-birth-weight newborns. The death rate for systemic Candida illnesses ranges from 29 to 76 percent. Just a few medications are available to treat it, such as amphotericin B, fluconazole, terbinafine, andcaspofungin, which have adverse reactions and are harmful. Objective: The goal of this research is to apply specialized bioinformatics approaches such as molecular docking, scaffold hopping, virtual screening, pharmacophore modeling, and molecular dynamics (MD) simulation to discover possibly novel and potent therapeutic drug candidates against Candida albicans in a shorter period and at a low cost. Methods: MDPI, MayBridge, Hitfinder, Mcule library, SQLite Database, DrugBank, ZINC, and NCI database were used to perform pharmacophore modeling, scaffold hopping, virtual screening, docking, and ADMET characteristics study against NMT. The molecular dynamics simulations for the best ten docked protein-ligand complexes were examined to determine the stability of protein-ligand interactions during a 200 ns simulation period, demonstrating their potential for lead molecule production via more improvement and experimental verification. Results: We have identified compound DB01940 ((3R,4R)-3-(4-hydroxybenzamido)azepan-4-yl 4-(2-hydroxybenzoyl)benzoate), DB01772 (3-(3-{[(2S)-2,3-dihydroxypropyl]amino}phenyl)-4-(5-fluoro-1-methyl-1H-indol-3-yl)-2,5-dihydro-1H-pyrrole-2,5-dione), and NCI5485 (1,3-bis((7-chloro-4-quinolinyl)amino)-2-propanol) could be more promising Candida albicans NMT inhibitors. Conclusion: In conclusion, these compounds have the potential to be effective anti-NMT medicines. The results demonstrate that our computational technique found some potential and effective NMT inhibitors that may be tested in clinical trials.

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In Silico Studies of Piperidine Derivatives as Protein Kinase B Inhibitors through 3D-QSAR, Molecular Docking and Molecular Dynamics Simulation

Cited by 4 publications

References 41 publications

Discovery of Novel 5,6-Dihydro-4H-pyrido[2,3,4-de]quinazoline Irreversible Inhibitors Targeting Both Wild-Type and A775_G776insYVMA Mutated HER2 Kinases

Discovery of Novel 5,6-Dihydro-4H-pyrido[2,3,4-de]quinazoline Irreversible Inhibitors Targeting Both Wild-Type and A775_G776insYVMA Mutated HER2 Kinases

Design, synthesis and biological evaluation of novel diaminopyrimidine derivatives as covalent fibroblast growth factor receptor 4 inhibitors

In silico Exploration of the Potential Inhibitory Activity of Novel Compounds Against Candida albicans N-myristoyltransferase

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