Chemical modification of the plant isoprenoid cytokinin N6-isopentenyladenosine yields a selective inhibitor of human enterovirus 71 replication

Abstract

In this study, we demonstrate that N(6)-isopentenyladenosine, which essentially is a plant cytokinin-like compound, exerts a potent and selective antiviral effect on the replication of human enterovirus 71 with an EC50 of 1.0 ± 0.2 μM and a selectivity index (SI) of 5.7. The synthesis of analogs with modification of the N(6)-position did not result in a lower EC50 value. However, in particular with the synthesis of N(6)-(5-hexene-2-yne-1-yl)adenosine (EC50 = 4.3 ± 1.5 μM), the selectivity index was significantly increased: because of a reduction in the adverse effect of this compound on the host cells, an SI > 101 could be calculated. With this study, we for the first time provide proof that a compound class that is based on the plant cytokinin skeleton offers an interesting starting point for the development of novel antivirals against mammalian viruses, in the present context in particular against enterovirus 71.

Effect of bioactive extracts with high cytokinin content from micelial biomass of Hericium coralloides and Fomitopsis officinalis on tumor cells in vitro

“…Cytokinins are known to change morphology and disorganize actin cytoskeleton of bladder carcinoma T24 cells, block DNA synthesis and increase the level of cyclinedependent kinase inhibitor and induce genes involved in a negative regulation of the cell cycle in tumour cells of epithelium [18][19][20]. Cytokinins also inhibit the human enterovirus replication, show immunostimulating effects promoting proliferation of natural killer cells, provoke apoptosis in myeloid leukemia HL-60 cells [21][22][23]. Thus, сomparing the data obtained with the literature, we can reasonably assume that the inhibitory effect of fungal extracts on tumor cells is associated with the presence of cytokinins in them.…”

Synthesis of Cytokinins via Enzymatic Arsenolysis of Purine Nucleosides

“…Recently, we have developed a useful and versatile approach for the preparation of N 6 ‐modified adenosine derivatives by the regioselective alkylation of N 6 ‐acetyl‐2′,3′,5′‐tri‐ O ‐acetyladenosine with alcohols under the Mitsunobu reaction conditions or by a base‐promoted reaction with alkyl halides (Drenichev et al., ; Drenichev et al., ; Tararov et al., ). The main advantage of N 6 ‐acetyl‐2′,3′,5′‐tri‐ O ‐acetyladenosine as a substrate is the possibility of using both alkyl halides and alcohols for the N 6 ‐modification, which is especially important in cases when an amine is unstable or is difficult or impossible to obtain.…”

Cytokinins phytohormones production by basidiomycetes micelial biomass

“…Вони змінюють морфологію й дезорганізують актиновий цитоскелет клітин карциноми сечового міхура [7], блокують синтез ДНК, підвищують рівень інгібітора циклінзалежної кінази [33], індукують гени, задіяні в негативній регуляції перебігу клітинного циклу ракових клітин епітелію [12]. Цитокініни також інгібують реплікацію ентеровірусу людини [35], чинять цитотоксичну та імуномодулювальну дію, сприяють проліферації природних клітин-кілерів [11]. Наведені відомості щодо лікувальних властивостей грибів і дані стосовно біологічної дії цитокінінів на клітини тварин і людини передбачають існування певного зв'язку між ними.…”