Design, Synthesis and Anticancer Evaluation of Nitroimidazole Radiosensitisers

The role of hypoxic tumour cells in resistance to radiotherapy, and in suppression of immune response, continues to endorse tumour hypoxia as a bona fide, yet largely untapped, drug target. Radiotherapy innovations such as stereotactic body radiotherapy herald new opportunities for classical oxygen-...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2023-05, Vol.28 (11), p.4457
Main Authors: Liew, Lydia P, Shome, Avik, Wong, Way W, Hong, Cho R, Hicks, Kevin O, Jamieson, Stephen M F, Hay, Michael P
Format: Article
Language:English
Subjects:
Alcohol
Biocompatibility
Cancer therapies
chemoradiotherapy
Chloride
Cytotoxicity
DNA damage
electron affinity
Hypoxia
Immune response
Nimorazole
Nitroimidazole
prodrugs
Radiation
Radiation therapy
Radiosensitization
Radiosensitizers
Sulfonamides
Therapeutic targets
Tumors
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Summary:The role of hypoxic tumour cells in resistance to radiotherapy, and in suppression of immune response, continues to endorse tumour hypoxia as a bona fide, yet largely untapped, drug target. Radiotherapy innovations such as stereotactic body radiotherapy herald new opportunities for classical oxygen-mimetic radiosensitisers. Only nimorazole is used clinically as a radiosensitiser, and there is a dearth of new radiosensitisers in development. In this report, we augment previous work to present new nitroimidazole alkylsulfonamides and we document their cytotoxicity and ability to radiosensitise anoxic tumour cells in vitro. We compare radiosensitisation with etanidazole and earlier nitroimidazole sulfonamide analogues and we identify 2-nitroimidazole and 5-nitroimidazole analogues with marked tumour radiosensitisation in ex vivo assays of surviving clonogens and with in vivo tumour growth inhibition.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules28114457