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Design and synthesis of some new piritrexim analogs as potential anticancer agents

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Abstract

The present study describes the synthesis and in vitro anticancer activity of novel piritrexim analogs against human breast cancer cell line MCF-7 and a normal Vero monkey cell line. The scheme involves the formation of 3-(4-nitrophenyl)-4-phenyl-1,8-naphthyridin-2-amine accomplished by the condensation reaction of 4-nitrophenyl acetonitrile, aromatic aldehyde, and 2-aminopyridine using acetic acid as a catalyst. The selected synthesized compounds have been screened against a human breast cancer cell line MCF-7 and a normal Vero monkey cell line, out of which the compounds 4b, 4e, 4f exhibited higher potency (GI50 [<10 µg/mL)], and compounds 4a, 4c show moderate to good activity (GI50 41.4 and 12.4 µg/mL) towards human breast cancer cell line MCF-7. Docking study on dihydrofolate reductase enzyme receptor (DHFR) and epidermal growth factor receptor reveals that compounds 4a, 4b, 4c, and 4e show moderate to good binding along with acceptable glide scores.

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Acknowledgements

One of the authors (PPW) thanks the Department of Science and Technology, New Delhi, for INSPIRE Fellowship (No. DST/INSPIRE Fellowship/2013/197). We gratefully thank ACTREC, Mumbai, India, for providing anticancer screening of compounds.

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Authors and Affiliations

  1. Department of Agrochemicals and Pest Management, Shivaji University, Kolhapur, Maharashtra, 416004, India

    Poojali P. Warekar, Kirti T. Patil & Priyanka T. Patil

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

    Aniket P. Sarkate & Kshipra S. Karnik

  3. Medicinal Chemistry Research Laboratory, Department of Chemistry, Shivaji University, Kolhapur, Maharashtra, 416004, India

    Santosh S. Undare, Govind B. Kolekar, Madhukar B. Deshmukh & Prashant. V. Anbhule

  4. Nielsen Neuroscience Ramdeveena, B 21, Ulsoor Rd, Bangalore, Karnataka, 560025, India

    Shivadatta Prabhu

  5. School of Nanoscience and Technology, Shivaji University, Kolhapur, Maharashtra, 416004, India

    Shivadatta Prabhu

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  1. Poojali P. Warekar
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Correspondence to Prashant. V. Anbhule.

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Warekar, P.P., Patil, K.T., Patil, P.T. et al. Design and synthesis of some new piritrexim analogs as potential anticancer agents. Res Chem Intermed 44, 749–767 (2018). https://doi.org/10.1007/s11164-017-3132-z

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  • DOI: https://doi.org/10.1007/s11164-017-3132-z

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