Insilico analysis of acridone against TNF-α and PDE4 targets for the treatment of psoriasis

Sukumaran, S.; Meghna, M; S, Sneha; Arjun, B; Sathianarayanan, S.; Saranya, T.S.

doi:10.26452/ijrps.v11ispl4.4286

Cited by 6 publications

(2 citation statements)

References 10 publications

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“…Schrödinger suite 2021-4, preparation of the Wizard module was used to prepare the protein [13]. The addition of hydrogen destroyed the crystallographic water molecules [14]. Prime (Schrödinger suite 2021-4) accommodated the missing side chain.…”

Section: Molecular Dockingmentioning

confidence: 99%

Design for the Colon Cancer Inhibitors Targeting Thymidylate Kinase by Using Insilico Studies

BAQI,

JAYANTHI,

RAJESHKUMAR

2024

Int J App Pharm

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Objective: Thymidylate Kinase (TMK) plays a crucial role in bacterial DNA synthesis by catalyzing the phosphorylation of Deoxythymidine Monophosphate (dTMP) to form Deoxythymidine Diphosphate (dTDP). Consequently, this enzyme emerges as a promising target for developing novel anti-cancer drugs. However, no anti-cancer drugs have been reported for this target until now. Methods: Ligands obtained from Benzylidene derivatives were examined for their potency by using molecular docking by glide module, Qikprop screening of Absorption, Distribution, Metabolism, and Excretion (ADME) study, and prime Molecular Mechanics in Generalized Bond Surface Area study (MM-GBSA) by binding free energy. Hereafter, a Molecular Dynamic (MD) simulation was performed at 100 ns to assess the stability of the potential ligand as a Human TMK (HaTMK) inhibitor. Results: These ten molecules showed good binding affinity and hydrogen and hydrophobic bond interactions with Arg150, Phe42, and Phe72 in the HaTMK enzyme (PDB id: 1E2D). Among them, trichloro-6-(((4-hydroxyphenyl)imino)methyl)phenol molecule had a high XP-docking score of (−7.87 kcal/mol), based on extra-precision data. Prime MM-GBSA studies also showed promising binding affinities i.e., ΔBind (-34.59 kcal/mol), ΔLipo (-13.92 kcal/mol), and ΔVdW (-34.42 kcal/mol). Arg76 and Phe72 residues maintained constant interactions with the ligand during Molecular Dynamics (MD) simulation. This ligand showed a potential binding affinity for the TMK target. Conclusion: The trichloro-6-(((4-hydroxyphenyl)imino)methyl)phenol ligand has active sites, namely benzene ring, benzylidene, and oxygen group, which actively participate in interaction with the protein of HaTMK, thus indicating good potential activity as the inhibitor of HaTMK to treat colon cancer.

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Section: Molecular Dockingmentioning

confidence: 99%

Design for the Colon Cancer Inhibitors Targeting Thymidylate Kinase by Using Insilico Studies

BAQI,

JAYANTHI,

RAJESHKUMAR

2024

Int J App Pharm

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“…Schrödinger suite 2019-2, preparation of the izard module was used to prepare the protein [18]. The addition of hydrogen destroyed the crystallographic water molecules [19]. Prime (Schrödinger suite 2019-2) accommodated the missing side chain.…”

Section: Molecular Dockingmentioning

confidence: 99%

Molecular Docking Dynamics of Selected Benzylidene Amino Phenyl Acetamides as TMK Inhibitors Using High Throughput Virtual Screening (Htvs)

JAYANTHI,

AHMED,

BAQI

et al. 2024

Int J App Pharm

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Objective: Thymidylate kinase (TMK) plays a crucial role in bacterial DNA synthesis by catalyzing the phosphorylation of deoxythymidine monophosphate (dTMP) to form deoxythymidine diphosphate (dTDP). Consequently, this enzyme emerges as a promising target for developing novel antibacterial drugs. However, no antibiotics were reported for this target, especially active against Staphylococcus aureus thymidylate kinase. Methods: Benzylidene acetamide-based ligands were examined for their potency using the in silico method. These novel ligand structures were built using ChemDraw software. The protein was retrieved from the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) website. The molecular docking and binding free energy calculation by prime Molecular Mechanics in Generalized Bond Surface Area (MM-GBSA) was performed for selected ligands. A 100 ns molecular dynamic simulation was also performed to assess the stability of the potential ligand as TMK inhibitors. Results: All ten molecules have shown good glide scores and hydrophobic and hydrogen hydrophobic hydrogen bonding interactions with Arg48, Arg36, and π-π stacking Phe66 in the TMK enzyme (PDB: 4HLC). Among them, N-(2-ethylphenyl)-2-(4-((4-nitrobenzylidene) amino) phenoxy) acetamide molecule had high XP-docking scores of-3.27 kcal/mol based on extra-precision data. Prime Molecular Mechanics in Generalized Bond Surface Area study (MM-GBSA) studies also showed promising binding affinities that are ΔBind (-65.80), ΔLipo (-28.55), and ΔVdW (-55.10). Phe66 amino acid residue maintained continuous connections with the ligand during MD simulation. This ligand showed promising binding affinity with the SaTMK target. Conclusion: The N-(2-ethylphenyl)-2-(4-((4-nitrobenzylidene) amino) phenoxy) acetamide ligand at the position of the benzene ring displayed nitrogen and oxygen group, thus indicating good potential activity as the inhibitor of TMK to treat antibacterial agents.

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Identification of Papain-Like Protease inhibitors of SARS CoV-2 through HTVS, Molecular docking, MMGBSA and Molecular dynamics approach

Jupudi

Rajagopal

Murugesan

et al. 2022

South African Journal of Botany

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Insilico analysis of acridone against TNF-α and PDE4 targets for the treatment of psoriasis

Cited by 6 publications

References 10 publications

Design for the Colon Cancer Inhibitors Targeting Thymidylate Kinase by Using Insilico Studies

Design for the Colon Cancer Inhibitors Targeting Thymidylate Kinase by Using Insilico Studies

Molecular Docking Dynamics of Selected Benzylidene Amino Phenyl Acetamides as TMK Inhibitors Using High Throughput Virtual Screening (Htvs)

Identification of Papain-Like Protease inhibitors of SARS CoV-2 through HTVS, Molecular docking, MMGBSA and Molecular dynamics approach

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