40 research outputs found
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
Cytotoxic activities of new iron(III) and nickel(II) chelates of some S-methyl-thiosemicarbazones on K562 and ECV304 cells
The S-methyl-thiosemicarbazones of the 2-
hydroxy-R-benzaldehyde (R= H, 3-OH 3-OCH3 or 4-OCH3)
reacted with the corresponding aldehydes in the presence of
FeCl3 and NiCl2. New ONNO chelates of iron(III) and nickel
(II) with hydroxy- or methoxy-substitued N1,N4-diarylidene-Smethyl-
thiosemicarbazones were characterized by means of
elemental analysis, conductivity and magnetic measurements,
UV-Vis, IR and 1H-NMR spectroscopies. Cytotoxic activities
of the compounds were determined using K562 chronic
myeloid leukemia and ECV304 human endothelial cell lines
by MTT assay. It was determined that monochloro N1-4-
methoxysalicylidene-N4-4-methoxysalicylidene-S-methylthiosemicarbazidato-
iron(III) complex showed selective
anti-leukemic effects in K562 cells while has no effect in
ECV304 cells in the 0.53 ÎŒg/ml (IC50) concentrations. Also,
some methoxy-substitued nickel(II) chelates exhibit high
cytotoxic activitiy against both of these cell lines in low
concentrations. Cytotoxicity data were evaluated depending on
cell lines origin and position of the substituents on aromatic rings
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The recovery of European freshwater biodiversity has come to a halt
Owing to a long history of anthropogenic pressures, freshwater ecosystems are among the most vulnerable to biodiversity loss. Mitigation measures, including wastewater treatment and hydromorphological restoration, have aimed to improve environmental quality and foster the recovery of freshwater biodiversity. Here, using 1,816 time series of freshwater invertebrate communities collected across 22 European countries between 1968 and 2020, we quantified temporal trends in taxonomic and functional diversity and their responses to environmental pressures and gradients. We observed overall increases in taxon richness (0.73% per year), functional richness (2.4% per year) and abundance (1.17% per year). However, these increases primarily occurred before the 2010s, and have since plateaued. Freshwater communities downstream of dams, urban areas and cropland were less likely to experience recovery. Communities at sites with faster rates of warming had fewer gains in taxon richness, functional richness and abundance. Although biodiversity gains in the 1990s and 2000s probably reflect the effectiveness of water-quality improvements and restoration projects, the decelerating trajectory in the 2010s suggests that the current measures offer diminishing returns. Given new and persistent pressures on freshwater ecosystems, including emerging pollutants, climate change and the spread of invasive species, we call for additional mitigation to revive the recovery of freshwater biodiversity