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Design, synthesis and biological evaluation of hydrazone derivatives as anti-proliferative agents

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Abstract

A series of triaryl-substituted hydrazones as structural acyclic prototypes were synthesized and screened for anti-proliferative activity against breast (Michigan cancer foundation-7 and MD Anderson metastatic breast-231) and uterine cancer (Ishikawa) cell lines. Two compounds were found to be the most active, 5e showed the maximum inhibition of both functional estrogen receptor containing Michigan cancer foundation-7 cells (IC50: 7.8 µM) and Ishikawa cells (IC50: 7.3 µM) whereas, compound 5i was selectively most active against ER-negative MD Anderson metastatic breast-231 cells (IC50: 4.7 µM). The inhibitory effect of 5e in breast cancer and uterine cancer cells was due to ER antagonistic action, also supported by molecular docking studies.

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Acknowledgements

The authors, RS and USS are grateful to CSIR for Senior research fellowships and to the Ministry of Health & Family Welfare for financial assistance for the biological screening of compounds. All the authors are thankful to Sophisticated Analytical Instrument Facility for spectroscopic analyses of the pure compounds.

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Authors and Affiliations

  1. Medicinal & Process Chemistry Division,CSIR-Central Drug Research Institute, Sector 10,Jankipuram Extension, Sitapur Road, Lucknow, Uttar Pradesh, 226031, India

    Ravi Shankar, Uma S. Singh & Kanchan Hajela

  2. Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India

    Ravi Shankar

  3. Department of Pharmaceutical Chemistry, Indo-Soviet College of Pharmacy, Moga, 142001, India

    Ravindra K. Rawal

  4. Endocrinology Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, 226031, India

    Preeti Chaudhary & Rituraj Konwar

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  1. Ravi Shankar
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  2. Ravindra K. Rawal
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  3. Uma S. Singh
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  4. Preeti Chaudhary
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  5. Rituraj Konwar
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  6. Kanchan Hajela
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Correspondence to Kanchan Hajela.

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Shankar, R., Rawal, R.K., Singh, U.S. et al. Design, synthesis and biological evaluation of hydrazone derivatives as anti-proliferative agents. Med Chem Res 26, 1459–1468 (2017). https://doi.org/10.1007/s00044-017-1866-1

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  • DOI: https://doi.org/10.1007/s00044-017-1866-1

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