2. Academic Validation
  3. Designing an anticancer Pd(II) complex as poly(ADP-ribose) polymerase 1 inhibitor

Designing an anticancer Pd(II) complex as poly(ADP-ribose) polymerase 1 inhibitor

  • Int J Biol Macromol. 2025 Mar:297:139885. doi: 10.1016/j.ijbiomac.2025.139885.
Shuangshuang Gai 1,  Peng Cao 2,  Xuwei Zhong 1,  YiCan Lin 1,  Benxin Lin 1,  Ming Jiang 3
Affiliations

Affiliations

  • 1 School of Biological and Food Engineering, Guangxi Science & Technology Normal University, Laibin, Guangxi 546199, China.
  • 2 School of Food and Health, Guilin Tourism University, Guilin, Guangxi 541006, China.
  • 3 School of Biological and Food Engineering, Guangxi Science & Technology Normal University, Laibin, Guangxi 546199, China. Electronic address: [email protected].
PMID: 39818402 DOI: 10.1016/j.ijbiomac.2025.139885
Abstract

Targeting DNA repair mechanisms, particularly PARP-1 inhibition, has emerged as a promising strategy for developing Anticancer therapies. we designed and synthesized two 2-thiazolecarboxaldehyde thiosemicarbazone palladium(II) complexes (C1 and C2), and evaluated their anti-cancer activities. These Pd(II) complexes exhibited potent PARP-1 enzyme inhibition and demonstrated considerable antiproliferative activity against various Cancer cell lines. In vivo studies using the A549 tumor xenograft model revealed that C2 effectively suppressed tumor growth and exhibited minimal systemic toxicity. Mechanistically, C2 induced A549 cell death through multiple pathways: cell cycle arrest, elevated intracellular Reactive Oxygen Species (ROS) levels, DNA damage induction, exacerbated DNA double-strand breakage via PARP-1 inhibition, mitochondrial membrane potential reduction, and ultimately Apoptosis. These findings provide a new design strategy for developing safe and highly effective PARP-1 inhibitors.

Keywords

Anticancer; DNA damage; PARP-1; Pd(II) complex.

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