Development of a series of flurbiprofen and zaltoprofen platinum(iv) complexes with anti-metastasis competence targeting COX-2, PD-L1 and DNA. Issue 33 (4th August 2022)

• Record Type: Journal Article
• Authors: Li, Zuojie; Li, Linming; Zhao, Wenhuan; Sun, Bin; Liu, Zhifang; Liu, Min; Han, Jun; Wang, Zhengping; Li, Dacheng; Wang, Qingpeng
• Is Part Of: Dalton transactions. Volume 51:Issue 33(2022)
• Page Start: 12604
• Page End: 12619
• Publication Date: 2022-08-04
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/d2dt00944g
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : Flurbiprofen platinum(iv ) hybrids exhibit effective antiproliferative and anti-metastasis activities targeting COX-2, PD-L1 and DNA, and exert great potential in boosting T-cell immunity. Abstract : To develop new anti-metastasis chemotherapeutic drugs, a series of flurbiprofen (FLP) and zaltoprofen (ZTP) platinum(iv ) complexes targeting COX-2, PD-L1 and DNA was prepared and investigated. Complex 2 with dual FLP ligands displays promising antitumor activities in vitro and exhibits much potential in overcoming drug resistance. More importantly, the antitumor evaluation in vivo demonstrates that complex 2 possesses promising inhibition of cancer growth and metastasis simultaneously. Further investigation of the mechanism revealed the multi-specific antitumor function of complex 2 . It exerts remarkable DNA damage after reduction to platinum(ii ) complex, and up-regulates the expression of p53 and γ-H2AX. Then, complex 2 promotes mitochondria-mediated apoptosis effectively by activating the Bcl-2/Bax/caspase3 pathway. Furthermore, inflammation in tumor tissues is restrained by the suppression of enzymes COX-2, MMP-9, NLRP3 and caspase1, which would favor the inhibition of tumor metastasis. Moreover, compound 2 boosts T-cell immunity by restraining PD-L1 expression, and further improving the density of CD3 + and CD8 + T cells in tumor tissues.