Heteroleptic Gold(I)-bisNHC complex with excellent activity in vitro, ex vivo and in vivo against endometrial cancer

Abstract

Endometrial cancer (EC), one of the most common gynaecologic malignancies, can seriously impair female health. Although great advances in EC therapy have been achieved, specific and effective drugs for the disease are still limited. Here, different types of gold(I)–NHC compounds originated from 4,5-bis (4-methoxyphenyl) imidazole were designed and synthesised to target EC. Interestingly, the heteroleptic gold(I)-bisNHC complex 10 was 10 times more toxic than cisplatin or auranofin towards Ishikawa cells. Ex vivo studies found that complex 10 was characterised with a stronger anticancer effect than auranofin in the EC organoid model. Additionally, in vivo studies showed that complex 10 possessed a stronger anticancer effect (IRT = 44.86%) than auranofin (IRT = 19.93%) in the xenograft model of EC. Mechanistically, complex 10 could suppress the expression of thioredoxin reductase (TrxR) and nuclear factor E2-related factor 2 (Nrf2) in vitro and in vivo, which are essentially involved in EC development. Collectively, our findings demonstrated that complex 10 is a gold-based complex with a strong anti-EC activity and has the potential to be regarded as a promising option for the treatment of EC.