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QM study and conformational analysis of an isatin Schiff base as a potential cytotoxic agent

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Abstract

Isatin is an important compound from the biological aspect of view. It is an endogenous substance and moreover; various pharmacological activities have been reported for isatin and its derivatives. In-vitro cytotoxic effects of the prepared isatin Schiff bases toward HeLa, LS180 and Raji human cancer cell lines has been reported in our previous work. 3-(2-(4-nitrophenyl)hydrazono) indolin-2-one was found to be the most potent one among the studied compounds (IC30 = 12.2 and 21.8 μM in HeLa and LS-180 cell lines, respectively). Obtained biological data could be well interpreted using docking binding energies toward vascular endothelial growth factor receptor (VEGFR-2); a key anticancer target being biologically investigated against various isatin derivatives. In the present work, quantum mechanical (QM) method including functional B3LYP in association with split valence basis set using polarization functions (Def2-SVP) was used to estimate individual ligand-residue interaction energies for the docked 3-(2-(4-nitrophenyl)hydrazono) indolin-2-one into VEGFR-2 active site. Results were further interpreted via calculated polarization effects induced by individual amino acids of the receptor active site. A fairly good correlation could be found between polarization effects and estimated binding energies (R2 = 0.7227). Conformational analysis revealed that 3-(2-(4-nitrophenyl) hydrazono) indolin-2-one might not necessarily interact with the VEGFR-2 active site in its minimum energy conformation.

Various interactions of a 3-(2-(4-nitrophenyl) hydrazono) indolin-2-one structure with VEGFR-2 active site have been evaluated in terms of individual ligand-residue binding energies using functional B3LYP in association with Def2-SVP basis set

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Acknowledgments

Financial supports of this project by research council of Shiraz University of Medical Sciences are acknowledged.

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Authors and Affiliations

  1. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, 3288-71345, Shiraz, Iran

    Ramin Miri & Nima Razzaghi-asl

  2. Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Ramin Miri & Nima Razzaghi-asl

  3. Faculty of Sciences, Ahvaz Branch, Islamic Azad University, Ahvaz, Iran

    Mohammad K. Mohammadi

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  1. Ramin Miri
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  2. Nima Razzaghi-asl
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  3. Mohammad K. Mohammadi
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Correspondence to Mohammad K. Mohammadi.

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Miri, R., Razzaghi-asl, N. & Mohammadi, M.K. QM study and conformational analysis of an isatin Schiff base as a potential cytotoxic agent. J Mol Model 19, 727–735 (2013). https://doi.org/10.1007/s00894-012-1586-x

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  • DOI: https://doi.org/10.1007/s00894-012-1586-x

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