Guanosine Derivatives as Immunostimulants. Discovery of Loxoribine

Purine Nucleoside Analogues; 9: Benzylation of N2-Acetyl-8-bromoguanine

“…The biological activity of 8-substituted derivatives of guanosine and modified guanines has been well established. These compounds have been reported to stimulate the humoral immune system 3,4 and to terminate leukemia cell proliferation through conversion to end-stage differentiat-ed cells. 5 Antiviral compounds, 6,7 potent purine nucleoside phosphorylase (PNP, EC 2.4.2.1) inhibitors, 8 and effective AGT protein (EC 2.1.1.63) inactivators 9 have been found among them.…”

Immunostimulating Agents: What Next?

“…Anderson and Capetola [I 21 ] described the activities of 7-allyl-8-oxoguanosine which, in various experimental models, exhibited adjuvant-like effects in enhancing antibody production in response to several antigens, even in the absence o f T lymphocytes, while being devoid of pyrogenicity and unable to exacerbate autoimmune manifestations. More recently, several related analogs of 7-allyl-8-oxoguanosine (loxoribine) have been synthesized by Chen et al [122] : 2',3'-ketals of loxoribine display a significant activity on their own, apparently without being cleaved to the free nucleoside.…”

Proliferação celular induzida por 8-oxoguanosina e 8-metilguanosina, dois produtos do ataque de radicais livres a ribonucleosídeos e RNA

“…Em 1986 foi descrita pela primeira vez a atividade imunobiológica de 7-metil-8-oxoguanosina (7-Me-8-0xoGuo), um composto com atividade mais eficiente que seu análogos monosubstituídos (Goodman & Hennen, 1986). Estudos de relações entre estrutura e atividade levaram ao desenvolvimento do análogo 7-alil-8-oxoguanosina (loxoribina) que foi patenteado (Chen et al, 1994).…”