9-Arylpurines as a novel class of enterovirus inhibitors.
Here we report on a novel class of enterovirus inhibitors that can be structurally described as 9-arylpurines. These compounds elicit activity against a variety of enteroviruses in the low microM range including Coxsackie virus A16, A21, A24, Coxsackie virus B3, and echovirus 9. Structure-activity relationship (SAR) studies indicate that a chlorine or bromine atom is required at position 6 of the purine ring for antiviral activity. The most selective compounds in this series inhibited Coxsackie virus B3 replication in a dose-dependent manner with EC(50) values around 5-8 microM. No toxicity on different cell lines was observed at concentrations up to 250 microM. Moreover, no cross-resistance to TBZE-029 and TTP-8307 CVB3 resistant strains was detected.
Aguado
Leire
L
Instituto de Quimica Medica (CSIC), Juan de la Cierva 3, E-28006 Madrid, Spain.
Thibaut
Hendrik Jan
HJ
Priego
Eva-María
EM
Jimeno
María-Luisa
ML
Camarasa
María-José
MJ
Neyts
Johan
J
Pérez-Pérez
María-Jesús
MJ
D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000145:classification* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004770:Enterovirus / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011687:Purines / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014709:Vero Cells
D000998:Antiviral Agents; D011687:Purines