Antiviral activity of platinum (II) and palladium (II) complexes of pyridine-2-carbaldehyde thiosemicarbazone

A heterocyclic compound, pyridine-2-carbaldehyde thiosemicarbazone (HFoTsc), and its six metal coordinated bound complexes, three with platinum (II) and three with palladium (II), were studied for their activity against herpes simplex virus 1 (HSV-1) infection in cultured cells. According to their cytotoxicity the compounds were divided into two groups. Group 1 (cytotoxic compounds) included all three palladium complexes and [Pt(HFoTsc)(2)] Cl-2, with maximum non-toxic concentration (MNC) of 1-10 mu mol/l and a 50% cytotoxic concentration (CC50) of 20-100 mu mol/l. Group 2 (low cytotoxic compounds) with MNC of 100 mu moL/l and CC50 of 548-5820 mu mol/l included compounds in the following order: [Pt(HFoTsc)(2)] Cl-2 <HFoTsc<[PtClFoTsc)]. The 50% inhibitory concentration (IC50) and a selectivity index (SI) values determined during 24 hrs and 48 hrs of action were indicative of antiviral activity IC50 and SI values of HFoTsc increased in parallel with the duration of action in HSV-1-infected cells. All three platinum complexes as well as [Pd(HFoTsc)(2)]Cl-2 and [Pd(FoTsc)(2)] inhibited HSV-1 infection following a structure-activity relationship but only [Pt(HFoTsc)(2)]Cl-2 expressed a significant selectivity comparable to that of HFoTsc. However, [PdCl(FoTsc)] acting 48 hrs gave a higher infectious HSV-1 titer (170%) compared to control (100%, no compound).