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Efficient synthesis of piperazine-2,6-dione and 4-(1H-indole-2-carbonyl)piperazine-2,6-dione derivatives and their evaluation for anticancer activity

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Abstract

Condensation of iminodiacetic acid 1 with various amines i.e., cyclohexanamine, 1-(3-aminopropyl)imidazole, pyridin-2-ylmethanamine, pyridin-3-ylmethanamine, pyridin-4-ylmethanamine, 2-morpholinoethanamine, thiophen-2-ylmethanamine, 2-(thiophen-2-yl)ethanamine, furan-2-ylmethanamine, 2-(pyrrolidin-1-yl)ethanamine, and 1-(3-aminopropyl) pyrrolidin-2-one 2a–k under microwave irradiation gave the corresponding piperazine-2,6-dione derivatives 3a–k in quantitative yields. Piperazine-2,6-dione derivatives 3a–k on condensation with 1H-indole-2-carboxylic acid under microwave irradiation gave the corresponding 4-(1H-indole-2-carbonyl)piperazine-2,6-dione derivatives 4a–k in quantitative yields. All the synthesized compounds (3a–k & 4a–k) were purified by crystallization and characterized by spectroscopic means. On screening at a concentration of 10 μM, compounds 3k, 4e, 4i breast (T47D), 4j lung (NCI H-522), 3i colon (HCT-15), 4e ovary (PA-1), and 4g liver (HepG-2) exhibited good anticancer activity.

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Acknowledgments

We are thankful to the technical staff of the Chemistry Department, I. I. T. Roorkee, for spectroscopic studies and elemental analysis and also to Head I. I. C. for providing NMR facility. Special thanks are due to Prof. G. Bhattacharjee and Prof. Ravi Bhushan of Chemistry Department, I. I. T. Roorkee, for helpful discussion. Mr. Sandeep Kumar is thankful to MHRD, New Delhi for financial assistance.

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Authors and Affiliations

  1. Department of Chemistry, Indian Institute of Technology-Roorkee, Roorkee, 247667, Uttrakhand, India

    Sandeep Kumar & Sham M. Sondhi

  2. Department of Biotechnology, Indian Institute of Technology-Roorkee, Roorkee, 247667, Uttrakhand, India

    Nikhil Kumar & Partha Roy

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  1. Sandeep Kumar
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  2. Nikhil Kumar
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  3. Partha Roy
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  4. Sham M. Sondhi
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Correspondence to Sham M. Sondhi.

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Kumar, S., Kumar, N., Roy, P. et al. Efficient synthesis of piperazine-2,6-dione and 4-(1H-indole-2-carbonyl)piperazine-2,6-dione derivatives and their evaluation for anticancer activity. Med Chem Res 22, 4600–4609 (2013). https://doi.org/10.1007/s00044-012-0438-7

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  • DOI: https://doi.org/10.1007/s00044-012-0438-7

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