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Design and synthesis of taxane derivatives of valproic acid as potent and selective cytotoxic agents

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Abstract

Resistance to anticancer agents has important implications for cancer chemotherapy. Small changes in chemical structures of cytotoxic agents can alter their biological interactions that can be beneficial in overcoming the drug resistance problem. Valproic acid, a well-known antiepileptic drug is in advanced clinical studies for cancer treatment. In the present study, valproic acid was incorporated into the taxane moiety at various positions and the new analogs were evaluated for their in vitro cytotoxicity. The novel analog, Valprotaxel showed comparable cytotoxicity in head and neck, and colon cancer cell lines with remarkable improvement in selectivity for cancer cells compared to paclitaxel and docetaxel.

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Acknowledgments

The research project was sponsored by Piramal Healthcare Limited. Authors wish to express their heartfelt thanks to Dr. Apparao Satyam for his guidance and valuable advice. The authors are very grateful to Dr. Rajeev Sharma, Dr. Arun Balakrishnan, Dr. H. Sivaramakrishanan, and Dr. Somesh Sharma for their encouragement for the research work. Special thanks to Ms. Diana Writer for her timely support and our colleagues of patents department who spontaneously facilitated the authors.

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Authors and Affiliations

  1. Pharmaceutical Chemistry Division, School of Advanced Sciences, VIT University, Vellore, Tamil Nadu, India

    Himaja Malipeddi, Sunil V. Mali & Moonjit Das

  2. Medicinal Chemistry Division, Piramal Healthcare Ltd., Goregaon, Mumbai, India

    Sunil V. Mali

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  1. Himaja Malipeddi
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  2. Sunil V. Mali
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  3. Moonjit Das
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Correspondence to Himaja Malipeddi.

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Malipeddi, H., Mali, S.V. & Das, M. Design and synthesis of taxane derivatives of valproic acid as potent and selective cytotoxic agents. Med Chem Res 25, 2512–2520 (2016). https://doi.org/10.1007/s00044-016-1635-6

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  • DOI: https://doi.org/10.1007/s00044-016-1635-6

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