含卤素苯乙酸的生物活性铂（IV）配合物。

Bioactive Platinum(IV) Complexes Incorporating Halogenated Phenylacetates.

机构信息

School of Science, Western Sydney University, Locked Bag 1797, Sydney, NSW 2751, Australia.

Ingham Institute, Sydney, NSW 2170, Australia.

出版信息

Molecules. 2022 Oct 21;27(20):7120. doi: 10.3390/molecules27207120.

DOI:10.3390/molecules27207120

PMID:36296713

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9611758/

Abstract

A new series of cytotoxic platinum(IV) complexes (-) incorporating halogenated phenylacetic acid derivatives (4-chlorophenylacetic acid, 4-fluorophenylacetic acid, 4-bromophenylacetic acid and 4-iodophenylacetic acid) were synthesised and characterised using spectroscopic and spectrometric techniques. Complexes - were assessed on a panel of cell lines including HT29 colon, U87 glioblastoma, MCF-7 breast, A2780 ovarian, H460 lung, A431 skin, Du145 prostate, BE2-C neuroblastoma, SJ-G2 glioblastoma, MIA pancreas, the ADDP-resistant ovarian variant, and the non-tumour-derived MCF10A breast line. The in vitro cytotoxicity results confirmed the superior biological activity of the studied complexes, especially those containing 4-fluorophenylacetic acid and 4-bromophenylacetic acid ligands, namely and , eliciting an average GI value of 20 nM over the range of cell lines tested. In the Du145 prostate cell line, exhibited the highest degree of potency amongst the derivatives, displaying a GI value of 0.7 nM, which makes it 1700-fold more potent than cisplatin (1200 nM) and nearly 7-fold more potent than our lead complex, (4.6 nM) in this cell line. Notably, in the ADDP-resistant ovarian variant cell line, (6 nM) was found to be almost 4700-fold more potent than cisplatin. Reduction reaction experiments were also undertaken, along with studies aimed at determining the complexes' solubility, stability, lipophilicity, and reactive oxygen species production.

摘要

一系列新的细胞毒性铂（IV）配合物（-）被合成并采用光谱和光谱技术进行了表征，其中包含卤化苯乙酸衍生物（4-氯苯乙酸、4-氟苯乙酸、4-溴苯乙酸和 4-碘苯乙酸）。配合物 - 被评估了一系列细胞系，包括 HT29 结肠、U87 神经胶质瘤、MCF-7 乳腺癌、A2780 卵巢、H460 肺癌、A431 皮肤、Du145 前列腺、BE2-C 神经母细胞瘤、SJ-G2 神经胶质瘤、MIA 胰腺、ADDP 耐药卵巢变体和非肿瘤衍生的 MCF10A 乳腺系。体外细胞毒性结果证实了所研究的配合物具有优异的生物活性，特别是那些含有 4-氟苯乙酸和 4-溴苯乙酸配体的配合物，即和，在测试的细胞系范围内产生平均 GI 值为 20 nM。在 Du145 前列腺细胞系中，衍生物中显示出最高的效力，表现出 GI 值为 0.7 nM，这使其比顺铂（1200 nM）强 1700 倍，比我们的先导配合物（4.6 nM）强近 7 倍。值得注意的是，在 ADDP 耐药卵巢变体细胞系中，（6 nM）被发现比顺铂强约 4700 倍。还进行了还原反应实验以及旨在确定配合物的溶解度、稳定性、亲脂性和活性氧物种产生的研究。