85 research outputs found
Zinc(II) Complexes - A New Group of Non-Mutagenic Herpes Simplex Virus Inhibitors
Former studies showed that complexes of Zn(II) with picolinic and with aspartic acids, Zn(pic)2 and Zn(asp)2, are able to inhibit HSV infection in cultured cells by affecting key steps of virus replication. As these complexes are candidates for a novel class anti-HSV drugs, further studies on their mutagenicity are of particular interest. In the present paper we present data showing that Zn(pic)2 and Zn(asp)2 do not express mutagenic effect in both prokaryotic (Salmonella typhimurium) and eukaryotic (Saccharomices cerevisiae) test systems
Effect of Copper Acyclovir Complexes on Herpes Simplex Virus Type 1 and Type 2 (HSV-1, HSV-2) Infection in Cultured Cells
We have found that when copper, zinc or cobalt is bound to a suitable ligand, the
appropriate complex exhibited a significant anti-HSV effect (Varadinova et al., 1993; 1996).
Recently published data by Sagripanti et al. (1997) also show that the inhibition of HSV by
copper was enhanced by reducing agents and that mechanism of the inactivation is similar
as for copper-mediated DNA damage (Aruoma, et al. 1991; Dizdaroglu, et al., 1991;
Toyokuni and Sagripanti, 1994). Therefore it was interesting to study the efect of Cu(ll)
coordination compounds with acyclovir (ACV) on the replication of HSV in cultured cells.
The experiments on cytotoxicity as well as on the activity of three different Cu-ACV
complexes [Cu(ACV)2Cl2(H2O)2] = (A); [Cu(ACV)2(H2O)3](NO3)2.H2O = (B) and [Cu(ACV)2(H2O)2](NO3)2] = (C) towards virus replication, with special attention on the growth of
ACV-resistant strain R-100 were performed on MDBK cells. ACV was used as a reference
compound. The following results were obtained: 1) Increased cellâs viability in the presence
of 20-40(g/ml ACV and decreased one in the presence of Cu-ACV complexes with relative
level (A) >> (B) > (C); 2) Cu-ACV complexes are more cytotoxic than the ligand - ACV and the
relative level is (C)>(B)>(A); 3) The anti-HSV effect of ACV can be modulated by copper at
levels depending on the specificity of the particular virus strain: (i) for the ACV sensitive strain
DA (HSV-1) - ACV ((A) > (C) > (B); (ii) for the ACV sensitive strain Bja (HSV-2) (A) > ACV > (C) > (B); (iii) for strain R-100 (ACVR, TKa) - (A) > ACV > (C) > (B). This findings are consistent with
previously published data and undoubtedly show that Cu-ACV complexes could be useful in
the treatment of HSV infections, especially when the causative agent is a resistant to ACV
mutant
Effect of Complexes of Zinc, Cobalt and Copper With D-Aminosugars on the Replication of Herpes Simplex Virus Type 1 (HSV-1)
Our previous results show that Zn(pic)2 and Zn(asp)2 inhibit key steps of the replication of HSV-1. Anti-HSV effect of complexes of Co(II) with aminoacids Lys and Ser was also found. In the present study we describe the effect of complexes of Zn(II), Co(II) and Cu(II) with D-aminosugars on the replication of HSV-1 and on the infectivity of free virions. The experiments were done using primary rabbit kidney cells (r.k.), diploid human embryonal fibroblasts (F) and Vero cells. No differences in the toxicity of metal complexes on diploid cells- r.k. and F, were found. Neither metal complexes, nor ligands-galactosoxime and glucosoxime, influenced the viral replication. During 1-4h prolonged contact only Cu(Gl.NOH)2 inactivated HSV-1 virions up to 90%. The results show that D-aminosugars are not suitable ligands for Zn(II), Cu(II) and Co(II) in respect of the inhibition of viral replication. However, only Cu(Gl.NOH)2 was able to inhibit the infectivity of free virions
Effect of Complexes of Cobalt With Aminoacids on the Replication of Herpes Simplex Virus Type 1 (HSV-1)
Cobalt, being essential metal, influences different physiological and enzymatic functions. As cobalt
does not accumulate in the body, Co-compounds have relatively low toxicity. The aim of the present
study is the effect of complexes of Co(II) with aminoacids - lysine, arginine, histidine and serine on
HSV-1 replication. No effect of [O2Co(his)4].nH2O and [O2Co(arg)2].nH2O on HSV-1 infection in vitro
was found. Both, [O2Co(lys)2].nH2O and [O2Co(ser)2].nH2O suppress the attachement of HSV-1
particles onto target cells and the viral replication as well. Moreover, the properties of the particular
Co-complex (charge, stability, structure) are manifestated by their virucidal effect. Thus,
[O2Co(ser)2].nH2O irreversibly inhibits the infectious activity of free HSV-1 virions, while virucidal
effect of [O2Co(lys)2].nH2O is completely reversible after the 2h of contact
Platinum(II) and Palladium(II) Complexes of Pyridine-2-Carbaldehyde Thiosemicarbazone as Alternative Antiherpes Simplex Virus Agents
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 strainsâtwo 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
Complexes of Zinc With Picolinic and Aspartic Acids Inactivate Free Varicella-Zoster Virions
Zn(II) picolinate and aspartate, Zn(pic)2 and Zn(asp)2, have been shown to inhibit key steps of the
replication of HSV-1. In the present study we describe the effect of Zn(pic)2 and Zn(asp)2 on the
replication of VZV and on the infectivity of free virions. The experiments are done using BHK-21
cells, a clinical isolate of VZV and Zn-complexes in concentration of 10 ÎŒM. When Zn-complexes
are present during the whole period of infection, the yield of infectious virus progeny decreases up
to 98%. The infectivity of VZV is completely restored after the removal of zinc. The virucidal effect is
manifested at the 2nd h of contact, when 90% of the virions are inactivated. The results show that
both Zn(pic)2 and Zn(asp)2 specifically inactivate free VZV virions with no effect on viral replication
Rosiglitazone and Pioglitazone Alter Aromatase Kinetic Properties in Human Granulosa Cells
We have previously reported that, in human granulosa cells, thiazolidinediones rosiglitazone and pioglitazone inhibit estrogen synthesis by interfering with androgen binding to aromatase, without an effect on aromatase mRNA or protein expression. In the current paper, we explore the effects of rosiglitazone and pioglitazone on the aromatase enzyme kinetic properties in human granulosa cells. The cells were incubated with various concentrations of testosterone or androstenedione, with or without rosiglitazone or pioglitazone. Estradiol and estrone concentrations in the conditioned tissue culture medium were measured by radioimmunoassay or immunosorbent assay. When testosterone was used as substrate, rosiglitazone or pioglitazone inhibited the Vmax by 35% (P < 0.001) and 24% (P < 0.001), respectively. When androstenedione was used as substrate, both rosiglitazone or pioglitazone inhibited Vmax by 13% (P < 0.007). We conclude that rosiglitazone or pioglitazone has no effect on Km but inhibits Vmax of aromatase in human granulosa cells, therefore, acting as noncompetitive inhibitors
Selectivity of a thiosemicarbazonatocopper(II) complex towards duplex RNA. Relevant noncovalent interactions both in solid state and solution
Thiosemicarbazones and their metal derivatives have long been screened as antitumor agents, and their interactions with DNA have been analysed. Herein, we describe the synthesis and characterization of compounds containing [CuL]+ entities (HL = pyridine-2-carbaldehyde thiosemicarbazone) and adenine, cytosine or 9-methylguanine, and some of their corresponding nucleotides. For the first time, crystal structures of adenine- and 9-methylguanine-containing thiosemicarbazone complexes are reported. To the best of our knowledge, the first study on the affinity thiosemicarbazoneâRNA is also provided here. Experimental and computational studies have shown that [CuL(OH2)]+ entities at low concentration intercalate into dsRNA poly(rA)·poly(rU) through strong hydrogen bonds involving uracil residues and ÏâÏ stacking interactions. In fact, noncovalent interactions are present both in the solid state and in solution. This behaviour diverges from that observed with DNA duplexes and creates an optimistic outlook in achieving selective binding to RNA for subsequent possible medical applications.Obra Social âla Caixaâ
(OSLC-2012-007), Ministerio de EconomĂa y Competitividad
and FEDER funds (CTQ2013-48937-C2-1-P, CTQ2015-70371-
REDT, MAT2012-34740 and CTQ2014-58812-C2-2-R), Junta de
Castilla y LeĂłn (BU237U13), the Basque Government (IT-779-
13), Gerencia Regional de Salud, ConsejerĂa de Sanidad, Junta
de Castilla y LeĂłn (GRS 1023/A/14 and GR172)
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