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Design, Synthesis and Anticancer Evaluation of Nitroimidazole Radiosensitisers.

ABSTRACT: 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.

SUBMITTER: Liew LP

PROVIDER: S-EPMC10254852 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Design, Synthesis and Anticancer Evaluation of Nitroimidazole Radiosensitisers.

Liew Lydia P LP Shome Avik A Wong Way W WW Hong Cho R CR Hicks Kevin O KO Jamieson Stephen M F SMF Hay Michael P MP

Molecules (Basel, Switzerland) 20230531 11

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 ...[more]

PMID: 37298933

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