Virtual Screening and ADMET studies to identify KSP inhibitors as anticancer therapeutics
Keywords:
KSP inhibitors, virtual screening, ADMET and Indolo PyrimidinesAbstract
To report the virtual screening of several series of Indolo Pyrimidine derivatives for in silico KSP inhibition to arrive at possible potential inhibitors of KSP with acceptable pharmacokinetic or ADMET properties. In order to identify potential inhibitors we employed various computational approaches. In this work, we computationally screened and analyzed 60 analogs and further tested their ADME/T profiles. Library of the molecules was constructed based upon structural modifications of pyrimidines and indole nucleus. Structural modifications were performed for the series of 4-(3- hydroxyphenyl)-6-methyl-2-oxo-N-substituted[(Z)-(2-oxoindolin-3-ylidene)amino]-3,4-dihydro- 1H-pyrimidine-5-carboxamide derivatives in an order to get better binding energies as compared with Ispinseb. The molecules with better (lower) binding energies were subjected to predict ADMET properties. Ten molecules from the series IP1-IP60 were found acceptable with binding energies and pharmacokinetic properties. On the basis of the binding energies and ADMET properties we have identified compound IP2 and IP4 to be the best interacting molecules. The molecules with acceptable ADMET properties and better binding energies were prioritized for synthesis and anticancer evaluation. The binding energies and ADMET of the drugs provided suggests the protein ligand binding interactions that can aid in the design and synthesis of more potential inhibitors.
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