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Synthesis, biological activity and docking study of some new isatin Schiff base derivatives

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Abstract

A set of novel Schiff bases of isatin were synthesized and characterized by reaction of isatin with various aromatic or heterocyclic primary amines. Cytotoxic activities for some of the synthesized compounds were evaluated by MTT assay in three human cancer cell lines (HeLa, LS180 and Raji). Half of the tested compounds showed good cytotoxicity in HeLa cells. 3-(2-(4-nitrophenyl) hydrazono) indolin-2-one was found to be the most potent molecule among the studied isatin derivatives. Docking studies of 3-substituted indolin-2-one scaffolds on vascular endothelial growth factor receptor 2 (VEGFR-2) involved in cell proliferation and angiogenesis was performed. 3-(naphthalen-1-ylimino) indolin-2-one and 3-(2-(4-nitrophenyl) hydrazono) indolin-2-one exhibited higher docking binding energies with receptor. For 3-(2-(4-nitrophenyl) hydrazono) indolin-2-one, H-bond interaction with Cys917 residue of target active site was in common with reported crystallographic benzoimidazole derivative (PDB code: 2OH4). New key H-bonds involving Glu915, Asn921, and Arg1049 residues in VEGFR-2 active site could be detected for 3-(2-(4-nitrophenyl) hydrazono) indolin-2-one. Extended lipophilic rings containing H-bond acceptors on the 3 position of indoline scaffold seemed to be important factors in developing potent VEGFR-2 inhibitors virtually. Based on the ligand efficiency indices, some isoxazole or thiazole substituted isatin derivatives may be regarded as efficient candidates for further molecular developments of anticancer agents.

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Acknowledgments

Financial supports of this project by research council of Shiraz University of Medical Sciences are acknowledged. We gratefully acknowledge the financial support from the Medicinal and Natural Products Chemistry Research Centre, Shiraz University of Medical Sciences.

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Authors and Affiliations

  1. Science and Research Branch, Department of Chemistry, Islamic Azad University, 11365-4435, Tehran, Iran

    Javad Azizian

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

    Mohammad K. Mohammadi

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

    Omidreza Firuzi & Ramin Miri

  4. Department of Medicinal Chemistry, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Nima Razzaghi-asl

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  1. Javad Azizian
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  2. Mohammad K. Mohammadi
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  3. Omidreza Firuzi
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  4. Nima Razzaghi-asl
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  5. Ramin Miri
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Correspondence to Ramin Miri.

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Azizian, J., Mohammadi, M.K., Firuzi, O. et al. Synthesis, biological activity and docking study of some new isatin Schiff base derivatives. Med Chem Res 21, 3730–3740 (2012). https://doi.org/10.1007/s00044-011-9896-6

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  • DOI: https://doi.org/10.1007/s00044-011-9896-6

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