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N-Benzylation of 6-aminoflavone by reductive amination and efficient access to some novel anticancer agents via topoisomerase II inhibition

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Abstract

Series of novel N-benzyl derivatives of 6-aminoflavone (9a–n) were synthesized and evaluated for anticancer and topoisomerase II enzyme inhibition activity. All the synthesized compounds were screened for in vitro anticancer activity against human breast cancer cell line (MCF-7) and human lung cancer cell line (A-549). Among the synthesized compounds, 9f and 9g were found to be the most potent anticancer agents against human breast cancer cell line (MCF-7) with IC50 values of 9.35 µM and 9.58 µM, respectively. Compounds 9b, 9c and 9n exhibited promising anticancer activity against human lung cancer cell line (A-549) with 43.71%, 46.48% and 44.26% inhibition at the highest concentration of 10 µM, respectively. Compounds 9c, 9f and 9g have ability to inhibit the topoisomerase II enzyme. Compound 9f showed most potent topoisomerase II enzyme inhibition activity with IC50 value of 12.11 µM. Further, these compounds have a high potential to be developed as a promising topoisomerase II inhibitors.

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Acknowledgements

We thank Dr. D. K. Mhaske, Dr. L. R. Patil (Maharaja Jivajirao Shinde College, Shrigonda) and Dr. R. J. Barnabas (Ahmednagar College, Ahmednagar) for their constant support. NMT acknowledges the financial support by BCUD, SPPU, Pune (Grant No: 13SCI 000031).

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Authors and Affiliations

  1. Department of Chemistry, Prof. John Barnabas Post Graduate School for Biological Studies, Ahmednagar College, Ahmednagar, Station Road, Ahmednagar, Maharashtra, 414001, India

    Nitin M. Thorat & Shankar R. Thopate

  2. Department of Chemistry, Maharaja Jivajirao Shinde Arts, Science, Commerce College, Shrigonda, Maharashtra, 413701, India

    Nitin M. Thorat

  3. Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, 431004, India

    Aniket P. Sarkate

  4. Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, 425405, India

    Deepak K. Lokwani

  5. Department of Pharmaceutical Chemistry, Durgamata Institute of Pharmacy, Dharmapuri, Parbhani, Maharashtra, 431401, India

    Shailee V. Tiwari

  6. Department of Animal Biology, University of Hyderabad, Hyderabad, 500046, India

    Rajaram Azad

  7. Department of Chemistry, Shri Sadguru Gangageer Maharaj Science, Gautam Arts and Sanjivani Commerce College, Kopargaon, Dist. Ahmednagar, Maharashtra, 423 601, India

    Shankar R. Thopate

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  1. Nitin M. Thorat
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Thorat, N.M., Sarkate, A.P., Lokwani, D.K. et al. N-Benzylation of 6-aminoflavone by reductive amination and efficient access to some novel anticancer agents via topoisomerase II inhibition. Mol Divers 25, 937–948 (2021). https://doi.org/10.1007/s11030-020-10079-1

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