Synthesis and antitumor mechanisms of two new 8-hydroxyquinoline platinum(ii) derivatives†

IF 2.7 3区化学 Q2 CHEMISTRY, MULTIDISCIPLINARY

New Journal of Chemistry Pub Date : 2025-03-17 DOI:10.1039/D4NJ04292A

Run-Chun Wu, Ju-Mei Zhang, Xiao-Qiong Huang, Qiu-Ming Li, Zhen Zhou, Hong Liang, Ming-Xiong Tan and Qi-Pin Qin

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Abstract

Herein, we report the design and synthesis of two new 8-hydroxyquinoline platinum(II) derivatives, namely [Pt(QCl)Cl₂]·CH₃OH (YLN1, YLN = Yulin Normal University) and [Pt(QBr)Cl₂]·CH₃OH (YLN2), with 2-[(5-chloropyridin-2-yl)-hydrazonomethyl]-quinolin-8-ol (QCl) and 2-[(5-bromopyridin-2-yl)-hydrazonomethyl]-quinolin-8-ol (QBr) as ligands, respectively. The cytotoxicity of YLN1 and YLN2 against MDA-MB-231 breast cancer cells (IC₅₀ = 5.49 ± 0.14 μM and 7.09 ± 0.24 μM) was found to be generally higher than against noncancer HL-7702 cells (IC₅₀ > 20.0 μM). Moreover, YLN1 and YLN2 induced senescence and apoptosis in MDA-MB-231 (MM231) cancer cells by significantly triggering DNA damage and downregulating hTERT mRNA expression, and the antitumor mechanisms of the Pt(II) complexes with different QCl and QBr ligands follows the order of YLN1 > YLN2. Taken together, we found the two new 8-hydroxyquinoline platinum(II) derivatives YLN1 and YLN2 as specific anticancer drugs targeting DNA damage response and hTERT suppression.

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两种新型8-羟基喹啉铂（ii）衍生物的合成及抗肿瘤机理

本文报道了以2-[（5-氯吡啶-2-基）-肼甲酰]-喹啉-8-醇（QCl）和2-[（5-溴吡啶-2-基）-肼甲酰]-喹啉-8-醇（QBr）为配体，设计合成了两种新的8-羟基喹啉铂（II）衍生物[Pt(QCl)Cl2]·CH3OH （YLN1, YLN =榆林师范大学）和[Pt(QBr)Cl2]·CH3OH （YLN2）。发现YLN1和YLN2对MDA-MB-231乳腺癌细胞的细胞毒性（IC50 = 5.49±0.14 μM和7.09±0.24 μM）普遍高于非肿瘤HL-7702细胞(IC50 >；20.0μM)。此外，YLN1和YLN2通过显著触发DNA损伤和下调hTERT mRNA表达诱导MDA-MB-231 （MM231）癌细胞衰老和凋亡，不同QCl和QBr配体Pt（II）复合物的抗肿瘤机制依次为YLN1 >；YLN2。综上所述，我们发现了两个新的8-羟基喹啉铂（II）衍生物YLN1和YLN2作为靶向DNA损伤反应和hTERT抑制的特异性抗癌药物。

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