Designing a multitarget In(iii) compound to overcome the resistance of lung cancer cells to cisplatin. Issue 2 (15th December 2022)

• Record Type: Journal Article
• Authors: Jiang, Ming; Zhang, Juzheng; Xu, Shihang; Li, Yanping; Li, Wenjuan; Liang, Hong; Yang, Feng
• Is Part Of: Dalton transactions. Volume 52:Issue 2(2023)
• Page Start: 269
• Page End: 280
• Publication Date: 2022-12-15
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/d2dt03374g
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : The In compound exerts a chemotherapeutic effect through multiple mechanisms in cisplatin-resistant lung cancer. Abstract : Designing novel anticancer non-platinum metal agents is fully challenging. Herein, a series of little-known indium (In) 2-acetylpyridine thiosemicarbazone compounds as potential anticancer agents were designed, synthesized, and characterized. The hydrogen atoms at the N-4 position with the alkyl of the In compounds significantly increased cellular uptake and cytotoxicity. In(iii ) compounds showed significantly higher cytotoxicity toward cisplatin-resistant cell lines than cisplatin. More importantly, C4 greatly inhibited A549DDP tumor growth in a vaccinated mouse model. C4 exerted cytotoxic effects via a multitarget mechanism. First, it activated p53 and blocked the cell cycle at the S phase, which then led to weak expression levels of cyclin and related kinases and upregulation of the expression levels of cyclin-dependent kinase inhibitors. C4 also depolarized the mitochondrial membrane potential and regulated the expression of the Bcl-2 family, which then released cyt-c and activated caspase-3/8/9 to execute apoptotic pathways. Then, it inhibited telomerase through the inhibition of the expression of the c-Myc regulator gene and expression of the human telomerase reverse transcriptase. Furthermore, C4 showed excellent antimetastatic activity.