Platinum(II) and Palladium(II) Complexes of Pyridine-2-Carbaldehyde Thiosemicarbazone as Alternative Antiherpes Simplex Virus Agents

Abstract

The cytotoxicity and the antivirus activity of Pd(II) and Pt(II) complexes with pyridine-2-carbaldehyde thiosemicarbazone (HFoTsc) against HSV replication were evaluated on four HSV strains—two wt strains Victoria (HSV-1) and BJA (HSV-2) and two ACVR mutants with different tk gene mutations R-100 (TKA, HSV-1) and PU (TKN, HSV-2). The experiments were performed on continuous MDBK cells and four HSV 1 and HSV 2 strains were used, two sensitive to acyclovir and two resistant mutants. The five complexes of HFoTsc, [Pt(FoTsc)Cl], [Pt(FoTsc)(H2FoTsc)]Cl2, [Pt(FoTsc)2], [Pd(FoTsc)(H2FoTsc)]Cl2, and [Pd(FoTsc)2], were found to be effective inhibitors of HSV replication. The most promising, active, and selective anti-HSV agent was found to be complex [Pt(FoTsc)(H2FoTsc)]Cl2. This complex could be useful in the treatment of HSV infections, since it is resistant to ACV mutants. PCR study of immediate early 300 bp ReIV Us1 region reveals that the complex [Pt(FoTsc)(H2FoTsc)]Cl2 specifically suppressed wt HSV-1 genome 2 hours after the infection, not inducing apoptosis/necrosis on the 8 hours after virus infection. The target was found to be most probably the viral, instead of the host cell DNA.

Synthesis, Characterization and Antimicrobial Studies of Copper (II) Complexes of Semicarbazone and Thiosemicarbazone of m- Hydroxy Benzaldehyde and p-Hydroxy Benzaldehyde

“…The synthesis of transition metal complexes with thiosemicarbazone ligands have been receiving considerable attention due to the pharmacological properties of both ligands and complexes [1][2][3] .The Chemistry of Thiosemicarbazone has received considerable attention because of their variable bonding modes, promising biological implications, structural diversity, and ion -sensing ability [4][5][6] .The ligand, based on semicarbazone and pyridoxal moieties(forms found in vitamin B6), has an enormous potential as a biologically active reagent as it has been demonstrated that transition metal complexes incorporating semicarbazones show biological activity. In particular, with regard to biological importance, nickel(II) complexes with semicarbazone ligands show antibacterial acivity 7 , and copper(II) complexes containing semicarbazones have also displayed biological properties [8][9][10][11] .…”

(E)-4-(Benzyloxy)benzaldehyde thiosemicarbazone

“…Data collection: APEX2 (Bruker, 2005); cell refinement: APEX2 ; data reduction: SAINT (Bruker, 2005); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL and PLATON (Spek, 2003 The chemistry of thiosemicarbazones have been of immense interest because these compounds provide intriguing chelating patterns, profound biomedical properties, structural diversity and ion-sensing abilities (Al-Awadi et al, 2008;Amoedo et al, 2006;Demertzi et al, 2007;Mirsha et al, 2006;Kizilcikli et al, 2004). Compounds of this type have been used as antibacterial, antifungal and antitumor agents (Sing et al, 2001;Offiong et al, 1997).…”

“…For related structures of thiosemicarbazones, see, for example: John et al (2003); Joseph et al (2004). For applications and bioactivities of thiosemicarbazones, see, for example: Al-Awadi et al (2008); Amoedo et al (2006); Chandra et al, (2001); Demertzi et al (2007); Kizilcikli et al (2004); Mirsha et al (2006); Offiong & Martelli (1997); Sing et al (2001). Hydrogen-bond geometry (Å , ).…”

Ru(II)‐p‐cymene Thiosemicarbazone Complexes as Inhibitors of Amyloid β (Aβ) Peptide Aggregation and Aβ‐Induced Cytotoxicity

“…Thiosemicarbazones are metal chelators and their derivatives quench reactive oxygen species . Copperbis(thiosemicarbazonato) complexes are found to reduce levels of Aβ peptide by up‐regulation of metalloproteases, which are mainly implicated in the degradation of Aβ peptide . A report revealed that bis(thiosemicarbazonato)copper complex, Cu(II)‐gtsm enhances neurite elongation and neuritogenesis in neuronal cells .…”