Multi-specific niflumic acid platinum(iv) complexes displaying potent antitumor activities by improving immunity and suppressing angiogenesis besides causing DNA damage. Issue 1 (6th December 2022)

• Record Type: Journal Article
• Authors: Li, Linming; Zhang, Ming; Jia, Dianlong; Liu, Zhifang; Zhang, Ning; Sun, Bin; Wang, Zhengping; Liu, Min; Wang, Qingpeng
• Is Part Of: Dalton transactions. Volume 52:Issue 1(2022)
• Page Start: 147
• Page End: 158
• Publication Date: 2022-12-06
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/d2dt03246e
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : Niflumic acid platinum(iv ) complexes exhibit effective antiproliferative and anti-metastatic activities by improving immunity, suppressing angiogenesis and causing serious DNA damage. Abstract : To develop new chemotherapeutics with anti-metastasis properties, a series of multi-specific niflumic acid (NFA) platinum(iv ) complexes with DNA damage, inflammation inhibition, immunity activation, and angiogenesis suppression mechanisms were designed, synthesized and evaluated as novel antitumor agents. The dual NFA platinum(iv ) complex with a cisplatin core showed promising antitumor activities both in vitro and in vivo with lower toxicity than platinum(ii ) drugs and displayed attractive anti-metastasis performance. It caused serious DNA damage and further elevated the expression of γ-H2AX. Furthermore, it promoted apoptosis by activating the mitochondrial apoptotic pathway and autophagy of tumor cells. Moreover, immune response in tumors was significantly improved by increasing CD3 +, CD4 + and CD8 + T infiltrating cells. Subsequently, the pathway ERK/HIF-1α/VEGFA associated with angiogenesis was suppressed by the reduced inflammation and elevated immune response, and the density of microvessels marked by CD34 was significantly reduced in tumors. Accordingly, the multi-specific NFA platinum(iv ) complexes have great potential to be developed as novel anti-proliferative and anti-metastatic drugs.