In-silico studies and docking of n-substituted isoindoline-1, 3-dioine analogues as anti-proliferative agents

Ajay Singh Sarthi, Swarnlata Saraf, Shreya Singh, Ritika Singh, Shailendra Saraf

University Institute of Pharmacy, Pt. RavishankarShukla University, Raipur, Chhattisgarh, India.

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Ajay Singh Sarthi, Swarnlata Saraf, Shreya Singh, Ritika Singh, Shailendra Saraf, 2024. In-silico studies and docking of n-substituted isoindoline-1, 3-dioine analogues as anti-proliferative agents. Journal of medical pharmaceutical and allied sciences, V 13 - I 1, Pages- 6292 – 6302. Doi: https://doi.org/10.55522/jmpas.V13I1.4651.

ABSTRACT

Recently,isoindoline-1,3-dione compounds based folpet, phosmet, captonand thalidomide were developed because they have a comparable degree of anti-proliferative efficacy owing to their diverse mechanisms such as HDAC inhibitors, tryptase inhibitors, inhibits the mode of tnf-α, and angiogenesis inhibitors. It was investigated how the phthalimide pharmacophore interacted with molecules such tnf-α, HDAC, VEGF, EGF, and Tyrosine Kinase Angiogenesis. In order to assess the inhibitory activity against enzyme assay, a series of phthalimidepharmacophores with various substituent’s (Schiff's base) at the N-phenyl ring were submitted to protein-ligand docking investigations using the lib-dock method in the current work. All of the compounds' chemical structures were designed using Cambridge software, ChemBioOffice Ultra 12.0, and their molecular characteristics were determined using the online molecular modelling tool Molinspiration. Utilizing the Discovery Studio Client version 4.1, ADMETlab 2.0, and Lazar 1.4.2 softwares, ADME, Toxicity, and Molecular Docking investigations using the lib-dock method were carried out to evaluate the binding mode and interactions of synthetic hits at the binding site of receptors. Docking studies demonstrated that these sorts of ligands interacted mostly with TNF-α, HDAC, VEGF, EGF, Tyrosine kinase, and angiogenesis reports, among others, by forming hydrogen bonds and interacting hydrophobically with the domain. Our docking results indicate that compounds A1, A10, A11, A22, A26, and A28 demonstrated the greatest binding affinity with the corresponding proteins based on the predicted binding energy. These computer simulations have shown that phthalimide compounds with N-phenyl rings replaced can effectively suppress enzymatic assay.

Keywords:

Phthalimide, ADME, Discovery Studio Client, Molecular Docking, Enzymatic assay

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