Adenosine N1-Oxide Analogues as Inhibitors of Orthopox Virus Replication

Abstract

Several new types of adenosine N 1 -oxide (ANO) derivatives including N 1 -alkoxy and N 6 -alkyl as well as the analogues with a trihydroxycyclopentane ring in place of the ribose residue were synthesized and their antiviral properties were evaluated in Vero and LLC-MK2 cell cultures infected with vaccinia, mousepox, monkeypox, cowpox, and different isolates of smallpox viruses. The antiviral activity of ANO and its derivatives significantly depended on the virus type and cell cultures. Mousepox and monkeypox viruses were the most sensitive to these compounds, while vaccinia and cowpox viruses were inhibited at the concentrations 1-1.5 orders of magnitude higher. The toxicity of the synthesized compounds was much lower than that of ANO. Modifications of the ANO N 6 -position did not offer any advantages over the parent compound. The synthesized N 1 -oxide derivatives of noraristeromycin retained the activity comparable with noraristeromycin and displayed a decreased toxicity. No direct correlation between antiviral activity and stability of the compounds was found.

Novel 5′-Norcarbocyclic Derivatives of Bicyclic Pyrrolo- and Furano[2,3-d]Pyrimidine Nucleosides

“…All the 5′-norcarbocyclic analogs of bicyclic furano- and pyrrolo[2,3d]pyrimidine nucleosides were synthesized starting from the general precursor racemic 1-(4′-hydroxy-2′-cyclopentene-1′-yl)-5-ioduracil 1 ( Figure 1 ) which was obtained as described earlier [ 12 , 13 ]. 1-(2′,3′,4′-Trihydroxycyclopent-1′-yl)-5-iodouracil 2 was synthesized by oxidation of compound 1 using osmium tetroxide in the presence of N -methylmorpholine- N- oxide (NMMO) [ 14 ]. This procedure allows the cis -2′,3′-diol to be obtained selectively [ 15 , 16 ].…”

“…1-(2′,3′,4′-Trihydroxycyclopent1’-yl)-5-iodouracil ( 2 ) was synthesized using the common procedure [ 14 ] 1 H-NMR(DMSO- d 6 ): 11.58 (1H, s, NH), 8.12 (1H, s, H6), 5.14 (1H, d, J = 4 Hz, OH), 4.95 (1H, d, J = 6 Hz, OH), 4.77 (1H, d, J = 4 Hz, OH), 4.73–4.68 (1H, m, H2′), 4.17–4.12 (1H, m, H1′), 3.82–3.79 (1H, m, H3′), 3.69–3.66 (1H, m, H4′), 2.43–2.40 (1H, m, H5′a), 1.42–1.37 (1H, m, H5′b).…”

Carbocyclic Analogues of Inosine-5’-Monophosphate: Synthesis and Biological Activity

“…9-(4’-Hydroxy-2’-cyclopenten-1’-yl)-6-chloropurine 3 was obtained via condensation of epoxycyclopentene and 6-chloropurine in accordance with the previously described procedure [4]. Refluxing of compound 3 in ethanol led to the formation of ester 4 , which subsequently reacted with the ethyl esters of tosyloxymethylphosphonic or iodomethylphosphonic acid, to yield monophosphonate 5 .…”

“…The starting 6-chloro-9-(4’-hydroxy-2’-cyclopenten-1’-yl)purine (3) was synthesized in accordance with the previously described methodology [ 4 ].…”

Update on monkeypox virus infection: Focusing current treatment and prevention approaches

“…It was shown to inhibit the replication and mRNA translation of MPXV [35]. Another study on Vero and LLC-MK2 cells showed significant efficacy of ANO and its derivatives on Mpox and mousepox virus infection and also inhibited the replication of other viruses including cowpox and vaccinia at higher doses [48]. It has been reported that ANO is an analog of S-adenosyl-L-homocysteine (SAH) hydrolases and suggested that ANO analogs may be effective in-vivo without major side effects [49].…”