Platinum(II)‐Acyclovir Complexes: Synthesis, Antiviral andAntitumour Activity

Abstract

A platinum(II) complex with the antiviral drug acyclovir was synthesized and its antiviral and anticancer properties were investigated in comparison to those of acyclovir and cisplatin. The platinum‐acyclovir complex maintained the antiviral activity of the parent drug acyclovir, though showing a minor efficacy on a molar basis (ID 50 = 7.85 and 1.02 μΜ for platinum‐acyclovir and cisplatin, respectively). As anticancer agent, the platinum‐acyclovir complex was markedly less potent than cisplatin on a mole‐equivalent basis, but it was as effective as cisplatin when equitoxic dosages were administered in vivo to P388 leukaemia‐bearing mice (%T/C = 209 and 211 for platinum‐acyclovir and cisplatin, respectively). The platinum‐acyclovir complex was also active against a cisplatin‐resistant subline of the P388 leukaemia (%T/C = 140), thus suggesting a different mechanism of action. The DNA interaction properties (sequence specificity and interstrand cross‐linking ability) of platinum‐acyclovir were also investigated in comparison to those of cisplatin and [Pt(dien)Cl] + , an antitumour‐inactive platinum‐triamine compound. The results of this study point to a potential new drug endowed, at the same time, with antiviral and anticancer activity and characterized by DNA interaction properties different from those of cisplatin.