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A synthetic approach and molecular docking study of hybrids of quinazolin-4-ones and thiazolidin-4-ones as anticancer agents

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Abstract

A series of 3-(4-(2-(aryl)-4-oxothiazolidin-3-yl)phenyl-2-phenylquinazolin-4(3H)-one derivatives were synthesized in appreciable yield by using anthranilic acid as a starting material. The structures of synthesized compounds (QT1–QT10) were confirmed on the basis of various spectral techniques and analytical methods. These synthesized compounds were screened for their in vitro antitumor activity against the human breast cancer cell line (MCF-7), human hepatocellular cancer cell line (HepG2) using MTT assay method and doxorubicin as a standard drug. Compound 3-(4-(2-(3-chlorophenyl)-4-oxothiazolidin-3-yl)phenyl-2-phenylquinazolin-4(3H)-one (QT4) showed comparable cytotoxic activity against Hep-G2 cell line. Compound 3-(4-(2-(4-methoxyphenyl)-4-oxothiazolidin-3-yl)phenyl-2-phenylquinazolin-4(3H)-one (QT5) showed comparable cytotoxic activity against MCF-7 cell line while QT6, QT7, QT8 were the less cytotoxic as they showed high IC50 and away from that of doxorubicin. The remaining compounds did not show significant activity against both the cell lines. To understand the interaction of series with active binding site of receptor, docking study was performed with topoisomerase-II co-crystallized with adenylyl-imidodiphosphate complex using AutoDockVina. There was a good correlation between in vitro and in silico study. Thus, this investigation leads to the identification of newer anticancer agents.

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Acknowledgement

We are thankful to Chairman, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar (Haryana) for providing necessary facilities to carry out this work. We are also thankful to Vivek Sharma, Assistant professor and Scientist in-charge, Animal cell culture laboratory, ISF college of Pharmacy, Moga for providing cell lines and facility for biological evaluation. One of the authors is getting financial assistance from Department of Science and Technology, New Delhi.

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Authors and Affiliations

  1. Drug Discovery and Research Laboratory, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science & Technology, Hisar, 125001, Haryana, India

    Samridhi Thakral, Deepika Saini, Ashwani Kumar & Sandeep Jain

  2. Department of Pharmaceutical Education and Research, Bhagat Phool Singh Women University, Khanpur Kalan, Sonepat, 131305, Haryana, India

    Neelam Jain

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  1. Samridhi Thakral
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  2. Deepika Saini
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Correspondence to Sandeep Jain.

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Thakral, S., Saini, D., Kumar, A. et al. A synthetic approach and molecular docking study of hybrids of quinazolin-4-ones and thiazolidin-4-ones as anticancer agents. Med Chem Res 26, 1595–1604 (2017). https://doi.org/10.1007/s00044-017-1857-2

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