2. Academic Validation
  3. Next-Generation Hypoxic Cell Radiosensitizers: Nitroimidazole Alkylsulfonamides

Next-Generation Hypoxic Cell Radiosensitizers: Nitroimidazole Alkylsulfonamides

  • J Med Chem. 2018 Feb 8;61(3):1241-1254. doi: 10.1021/acs.jmedchem.7b01678.
Muriel Bonnet 1,  Cho Rong Hong 1,  Way Wua Wong 1,  Lydia P Liew 1 2,  Avik Shome 1,  Jingli Wang 1,  Yongchuan Gu 1 2,  Ralph J Stevenson 1,  Wen Qi 3,  Robert F Anderson 1 3 2,  Frederik B Pruijn 1 2,  William R Wilson 1 2,  Stephen M F Jamieson 1 4 2,  Kevin O Hicks 1 2,  Michael P Hay 1 2
Affiliations

Affiliations

  • 1 Auckland Cancer Society Research Centre, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland , Private Bag 92019, Auckland, New Zealand.
  • 2 Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland , 3 Symonds St, Auckland, New Zealand.
  • 3 School of Chemical Sciences, Faculty of Science, University of Auckland , Private Bag 92019, Auckland, New Zealand.
  • 4 Department of Pharmacology and Clinical Pharmacology, School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland , Private Bag 92019, Auckland, New Zealand.
PMID: 29253343 DOI: 10.1021/acs.jmedchem.7b01678
Abstract

Innovations in the field of radiotherapy such as stereotactic body radiotherapy, along with the advent of radio-immuno-oncology, herald new opportunities for classical oxygen-mimetic radiosensitizers. The role of hypoxic tumor cells in resistance to radiotherapy and in suppression of immune response continues to endorse tumor hypoxia as a bona fide, yet largely untapped, drug target. Only nimorazole is used clinically as a radiosensitizer, and there is a dearth of new radiosensitizers in development. Here we present a survey of novel nitroimidazole alkylsulfonamides and document their cytotoxicity and ability to radiosensitize anoxic tumor cells in vitro. We use a phosphate prodrug approach to increase aqueous solubility and to improve tumor drug delivery. A 2-nitroimidazole and a 5-nitroimidazole analogue demonstrated marked tumor radiosensitization in either ex vivo assays of surviving clonogens or tumor regrowth delay.

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