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吡啶-2-甲醛缩氨基硫脲的铂(II)和钯(II)配合物的抗病毒活性

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

作者信息

Varadinova T, Kovala-Demertzi D, Rupelieva M, Demertzis M, Genova P

机构信息

Laboratory of Virology, Faculty of Biology, Sofia University, Bulgaria.

出版信息

Acta Virol. 2001 Apr;45(2):87-94.

Abstract

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 I (cytotoxic compounds) included all three palladium complexes and [Pt(HFoTsc)2] Cl2, with maximum non-toxic concentration (MNC) of 1-10 micromol/l and a 50% cytotoxic concentration (CC50) of 20-100 micromol/l. Group 2 (low cytotoxic compounds) with MNC of 100 micromol/l and CC50 of 548-5820 micromol/l included compounds in the following order: [Pt(HFoTsc)2] Cl2<HFoTsc<[PtC] FoTsc)]. 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]Cl2 and [Pd(FoTsc)2] inhibited HSV- I infection following a structure-activity relationship but only [Pt(HFoTsc)2]Cl2 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).

摘要

研究了一种杂环化合物吡啶 - 2 - 甲醛硫代半卡巴腙(HFoTsc)及其六种金属配位结合的配合物,其中三种与铂(II)配位,三种与钯(II)配位,考察了它们对培养细胞中单纯疱疹病毒1型(HSV - 1)感染的活性。根据细胞毒性,这些化合物被分为两组。第一组(细胞毒性化合物)包括所有三种钯配合物和[Pt(HFoTsc)2]Cl2,其最大无毒浓度(MNC)为1 - 10微摩尔/升,50%细胞毒性浓度(CC50)为20 - 100微摩尔/升。第二组(低细胞毒性化合物),MNC为100微摩尔/升,CC50为548 - 5820微摩尔/升,包括以下顺序的化合物:[Pt(HFoTsc)2]Cl2 < HFoTsc < [PtC]FoTsc)。在作用24小时和48小时期间测定的50%抑制浓度(IC50)和选择性指数(SI)值表明了抗病毒活性。在HSV - 1感染细胞中,HFoTsc的IC50和SI值随作用时间平行增加。所有三种铂配合物以及[Pd(HFoTsc)2]Cl2和[Pd(FoTsc)2]均遵循构效关系抑制HSV - 1感染,但只有[Pt(HFoTsc)2]Cl2表现出与HFoTsc相当的显著选择性。然而,作用48小时时,[PdCl(FoTsc)]产生的感染性HSV - 1滴度(170%)高于对照(100%,无化合物)。

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