Auckland Cancer Society Research Centre, The University of Auckland, Auckland 1023, New Zealand.
Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland 1010, New Zealand.
Molecules. 2023 May 31;28(11):4457. doi: 10.3390/molecules28114457.
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.
缺氧肿瘤细胞在放疗抵抗和免疫反应抑制中的作用，使肿瘤缺氧继续成为一个真实存在但尚未被充分利用的药物靶点。立体定向体部放射治疗等放射治疗的创新为经典的氧模拟放射增敏剂带来了新的机遇。只有尼莫佐唑临床上被用作放射增敏剂，而开发中的新放射增敏剂却很少。在本报告中，我们扩展了以前的工作，提出了新的硝基咪唑烷磺酰胺，并记录了它们在体外对缺氧肿瘤细胞的细胞毒性和放射增敏作用。我们比较了放射增敏作用与乙硝唑和早期的硝基咪唑烷磺酰胺类似物，并确定了具有明显肿瘤放射增敏作用的 2-硝基咪唑和 5-硝基咪唑类似物，这些类似物在体外存活克隆形成和体内肿瘤生长抑制的实验中得到了验证。
