Polysulfonates Derived from Metal Thiolate Complexes as Inhibitors of HIV-1 and Various other Enveloped Viruses In Vitro

Abstract

Sodium 2-mercaptoethanesulfonate reacts with the metal ions Pd(II), Pt(II), Ag(I), Cd(II) and Zn(II) to yield complexes containing multiple anionic sulfonate sites. On the basis of spectroscopic and other analytical data the complexes were assigned the tentative molecular formulas: Pd6(SCH2CH2SO3Na)12, Ptn(SCH2CH2SO3Na)2n+2, Agn(SCH2CH2SO3Na)n, Na2Zn4(SCH2CH2SO3Na)10, and Na2Cd4(SCH2CH2SO3Na)10. The complexes displayed a variety of differences in activity towards DNA and RNA viruses. The platinum complex showed no measurable cytotoxicity and exhibited a spectrum of antiviral activity resembling that of dextran sulfate. It was active against HIV-1 and HIV-2, herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), thymidine kinase-deficient HSV-1, human cytomegalovirus, vesicular stomatitis virus (VSV), influenza A virus, respiratory syncytial virus (RSV), Sindbis virus, Junin virus and Tacaribe virus. The palladium complex also showed no measurable cytotoxicity, but was completely inactive against most viruses, with one notable exception: both HIV-1 and HIV-2 were substantially inhibited by the palladium complex. The silver complex showed significantly less antiviral activity and greater cytotoxicity than the platinum complex but did show some selectivity against RSV. The zinc complex showed only modest activity against VSV, RSV, Junin virus, and Tacaribe virus, and like the silver compound was more cytotoxic than either the platinum or palladium complex. The cadmium complex was toxic to all of the cell lines used for in vitro evaluation of antiviral activity. Based on these results, the platinum and palladium compounds appear to be promising candidates for further studies, that is, as vaginal microbicides in the prevention of genital HIV and/or HSV transmission.

2-Mercaptoethanesulfonate (MES) anion-functionalized silver nanoparticles as an efficient SERS-based sensor of metal cations

“…It is also used as a mucolytic agent in acute or chronic pulmonary disease and sold as Mistabron. Moreover, 2-mercaptoethanesulfonate anions form complexes with various metal ions (Pd(II), Pt(II), Ag(I), Cd(II) and Zn(II)) and some of them (including Ag complexes) show negligible cytotoxicity and antiviral activity [24]. Thus, metal nanoparticles functionalized with MES are promising candidates in biological or biomedical applications.…”

Synthesis, characterization and binding studies of novel diorganotin(IV) complexes of sodium 2‐mercaptoethanesulfonate

“…MESNA can form complexes with metal ions such as Pd(II), Pt(II), Ag(I), Cd(II) and Zn(II) with multiple anionic sulfonate sites. The platinum complex exhibited less cytotoxicity but impressive antiviral activity against HIV‐1 and HIV‐2, herpes simplex virus type 1 (HSV‐1) and HSV‐2, human cytomegalo virus, vesicular stomatitis virus (VSV), influenza A virus, respiratory syncytial virus (RSV), Sindbis virus, Junin virus and Tacaribe virus . The palladium complex of MESNA is found active against both HIV‐1 and HIV‐2 and zinc complex is moderately active against VSV, RSV, Junin virus, and Tacaribe virus.…”

“…The palladium complex of MESNA is found active against both HIV‐1 and HIV‐2 and zinc complex is moderately active against VSV, RSV, Junin virus, and Tacaribe virus. The silver compound was found more cytotoxic as compared platinum and palladium complexes, and cadmium complex was found toxic to all the cell lines used for evaluation of antiviral activity in vitro . Few hydrated di‐ and triorganotin(IV) complexes of MESNA have been tested in vivo in P‐388 leukaemic mice where the complexes with diphenyltin and dimethyltin moieties were found to be cytotoxic towards the cancer cells .…”

Transition‐Metal Complexes Based on a Sulfonate‐Containing N‐Donor Ligand and Their Use as HIV Antiviral Agents

“…For instance, (2-mercaptoethanesulfonato)platinum or -palladium complexes act as inhibitors of HIV-1, exhibiting antiviral activity similar to that shown by dextran sulfate. [5] Sulfonated naphthylporphyrins and their copper and iron chelates [6] and (sulfonated triazine)platinum complexes, [7] in which the sulfonated groups are not directly bonded to the transition metal atom, have also shown good potential as microbicides. Another approach involves the use of bicyclam ligands like AMD3100, which is extremely specific in its affinity for the CXCR4 co-receptor although this behaviour can be enhanced by coordination to Cu 2+ , Zn 2+ or Ni 2+ metal ions.…”