| Literature DB >> 29253343 |
Muriel Bonnet1, Cho Rong Hong1, Way Wua Wong1, Lydia P Liew1,2, Avik Shome1, Jingli Wang1, Yongchuan Gu1,2, Ralph J Stevenson1, Wen Qi3, Robert F Anderson1,3,2, Frederik B Pruijn1,2, William R Wilson1,2, Stephen M F Jamieson1,4,2, Kevin O Hicks1,2, Michael P Hay1,2.
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.Entities:
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Year: 2018 PMID： 29253343 DOI： 10.1021/acs.jmedchem.7b01678
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446