Oral Presentation Royal Australian Chemical Institute National Congress 2026

Synthesis, Characterization, and Biological Evaluation of Gold(I) Amidinate Complexes (136922)

Mona Rezaee 1 , Ruchika Ojha 1 , Suresh Bhargava 1 , Magdalena Plebanski 2 , Pooran Kumar 1
  1. Centre for Advanced Materials and Industrial Chemistry (CAMIC), RMIT University, Melbourne, Victoria, Australia
  2. Cancer, Ageing and Vaccines Research Group, School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia

Platinum-based chemotherapeutic agents such as cisplatin remain widely used in cancer treatment but are limited by severe toxicity and the development of drug resistance. Gold(I) complexes have emerged as promising alternatives due to their distinct, non-DNA-targeting mechanisms, particularly inhibition of redox-regulating enzymes. However, gold(I) complexes featuring Au-N coordination remain poorly explored, and gold(I) amidinate systems have not previously been evaluated for anticancer activity. Herein, we report the synthesis, characterization, and biological evaluation of a new series of mononuclear gold(I) amidinate-phosphine complexes of the general formula [Au{(ArN=C(H)NAr)}(PR3), where Ar denotes substituted phenyl rings and PR3 = PPh3, P(p-F-C6H4)3, P(p-OMe-C6H4)3, or 1,3,5-triaza-7-phosphaadamantane (PTA). All complexes were obtained in good yields and fully characterised by 1H and 31P{1H} NMR spectroscopy, with characteristic upfield 31P shifts confirming coordination. The complexes displayed excellent stability in DMSO for up to 72 hours, and selected compounds were structurally confirmed by single-crystal X-ray diffraction. Antiproliferative activity was assessed against HeLa, PC3, and cisplatin-resistant A2780-cis cancer cell lines using the MTT assay. While the free ligands were inactive, several gold(I) complexes exhibited cytotoxicity comparable to or exceeding cisplatin. Notably, triphenylphosphine-containing complexes showed strong activity against A2780-cis cells, indicating potential to overcome platinum resistance, whereas PTA-based complexes were inactive. These results identify gold(I) amidinate complexes as a promising and previously unexplored platform for anticancer drug development.