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Synthesis, crystal structure, anticancer and molecular docking studies of quinolinone-thiazolidinone hybrid molecules

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Abstract

A new series of quinolone-thiazolidinone hybrid molecules 8a-o were prepared. Quinoline compounds were synthesized by Meth-Cohn synthesis and were condensed with 2,3-disubstituted thiazolidinone. These molecules were screened for their anticancer activities against MDA-MB-231 and MCF-7 cell line using MTT assay. Potent compounds were tested for their cytotoxicity on normal HEK 293 cell lines and most potent compound was tested for its cell cycle analysis. Molecular docking and molecular dynamic studies were performed on human N-acetyl transferase (hNAT-1) protein using Schrodinger molecular docking toolkit. Compound 8n emerged as potent with IC50 8.16 µM against MDA-MB-231 cell line followed by 8e with IC50 17.68 µM. Compound 8n arrested cell cycle at G2/M phase and was non-toxic to human normal kidney cell line. The potent compound 8n binds well with human NAT-1 protein with remarkable hydrogen bonding and π–π interactions. Molecular dynamic studies of 8n further confirm the target for these molecules. Target quinolinone-thiazolidinones were found to be new class of compounds targeting hNAT-1 and can serve as new lead compounds in drug discovery.

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Acknowledgements

Authors are thankful to Yenepoya Research Centre, Yenepoya University, Deralakatte for helping in carryout anticancer activity. Also thankful to IOE and DST-PURSE, Vijnana Bhavana, University of Mysuru for X-ray crystallographic facility.

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Authors and Affiliations

  1. PG Department of Chemistry, Sri Dharmasthala Manjunatheshwara College (Autonomous), Ujire, India, 574240

    Vasantha Kumar

  2. Department of Microbiology, St. Aloysius College (Autonomous), Mangalore, 575003, India

    Vaishali M. Rai

  3. Department of Biotechnology and Microbiology, Sri Dharmasthala Manjunatheshwara Centre for Research in Ayurveda & Allied Sciences, Kuthpady, 574118, Udupi, Karnataka, India

    Vishwanatha Udupi

  4. Department of Physics, Faculty of Engineering & Technology, JAIN (Deemed-to-be University), Jain Global Campus, Ramanagara Dist., Bangalore, 562112, India

    Naveen Shivalingegowda

  5. Department of Biochemistry, Yenepoya Medical College, Yenepoya University, Deralakatte, Mangalore, 575018, India

    Vinitha R. Pai

  6. Department of Studies in Physics, University of Mysore, Manasagangotri, Mysuru, 570006, India

    Lokanath Neratur Krishnappagowda

  7. Department of Studies and Research in Chemistry, Mangalore University, Mangalagangothri, Karnataka, 574199, India

    Boja Poojary

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  1. Vasantha Kumar
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Kumar, V., Rai, V.M., Udupi, V. et al. Synthesis, crystal structure, anticancer and molecular docking studies of quinolinone-thiazolidinone hybrid molecules. J IRAN CHEM SOC 19, 793–808 (2022). https://doi.org/10.1007/s13738-021-02342-5

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