Phenanthriplatin is a monovalent platinum(II)-based complex with a large cytotoxicity against cancer cells[1].
Phenanthriplatin is a cationic monofunctional DNA-binding platinum (II) complex with significantly greater anticancer activity (IC50 in μM = 0.035/Ntera2, 0.22/A549, 0.30/HeLa, 0.59/U2OS, 0.74/PC3, 0.94/MCF7, 2.02/HT29; 72 h, MTT assay) than cisplatin, oxaliplatin, and pyriplatin. Enhanced cellular uptake due to its hydrophobic phenanthridine ligand as well as more rapid DNA covalent-binding activity both contribute to its superior anticancer efficacy. Phenanthriplatin binds more effectively to 5μ-deoxyguanosine monophosphate than to N-acetyl methionine, whereas pyriplatin reacts equally to both.
This potent Pt(II) complex (FW = 505.82 g/mol; CAS 1416900-51-0), also known as cis-diamminephenanthridinechloroplatinum(II), penetrates cell membranes either by passive diffusion or carrier-mediated active transport, with the hydrophobic ligand maximizing cellular uptake and making it cytotoxic compared with cisplatin and carbinatoplatin. Its molecular structure was designed with based the X-ray structure of RNA polymerase II (Pol II), when stalled at a monofunctional pyriplatin-DNA adduct. Phenanthriplatin interacts with guanine residues, forming highly potent, monofunctional DNA adducts. While many Pol II elongation complexes stall after successful addition of CTP opposite the phenanthriplatin-dG adduct in an error-free manner, a few slowly undergo error-prone bypass of the phenanthriplatin-dG lesion, a behavior that resembles DNA polymerases that similarly switch from high-fidelity replicative DNA processing (errorfree) to low-fidelity translesion DNA synthesis (error-prone) at DNA damage sites
[1] Veclani D, et al. Intercalation Ability of Novel Monofunctional Platinum Anticancer Drugs: A Key Step in Their Biological Action. J Chem Inf Model. 2021;61(9):4391-4399. DOI:
10.1021/acs.jcim.1c00430
