Platinum agent traps DNA AP sites, bypassing APE1 and cisplatin resistance
- Benzoquinoplatin, a benzoquinoline carrying a monofunctional platinum(II) group, covalently traps abasic DNA sites so APE1 can no longer cleave them; the enzyme itself is not inhibited.
- In cancer cells it caused sustained DNA-damage signalling, cell cycle arrest and apoptosis, and was far more potent than cisplatin.
- It stayed active in cisplatin-resistant cells and slowed resistant xenograft growth.
- Combining it with PARP inhibition was synergistic.
💡 Points Based on the abstract
Trapping AP sites sidesteps the usual enzyme-inhibitor problem, but a monofunctional platinum adduct raises the selectivity question: what keeps it from reacting with other DNA sites, proteins or thiols? I'd want repair-deficient versus proficient isogenic pairs, normal-cell toxicity and some exposure data before believing the xenograft result. The PARP synergy is plausible, yet it may also add marrow toxicity.