Inhibition of sickling in vitro by three purine-based antiviral agents: an approach to the treatment of sickle cell disease.
As a result of an in vitro screening effort the antiviral agent acyclovir was found to inhibit aggregation of hemoglobin S and the sickling of erythrocytes from individuals with sickle cell disease. Sickling of the erythrocytes was significantly inhibited at 200 microg/ml under essentially anaerobic conditions, considerably more hypoxic than the conditions in which sickling occurs in sickle cell patients. The structurally related guanine-based antiviral agents ganciclovir, valacyclovir, and penciclovir were also tested. Valacyclovir and ganciclovir showed comparable anti-sickling activity at concentrations similar to that of acyclovir. An examination of the shared structural characteristics of the four guanine derivatives linked anti-sickling activity to the presence of an oxygen atom alpha to the N9 of the guanine moiety. These findings suggest a new approach in the search for new agents for the treatment of patients with sickle cell disease.
DeBellis
Robert H
RH
Department of Medicine, Columbia University, New York, NY 10032, USA.
Chen
Bi-Xing
BX
Erlanger
Bernard F
BF
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000755:Anemia, Sickle Cell / Q000188:drug therapy* / Q000473:pathology; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002449:Cell Aggregation; D002469:Cell Separation; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015774:Ganciclovir / Q000737:chemistry / Q000494:pharmacology; D006451:Hemoglobin, Sickle / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D010100:Oxygen / Q000378:metabolism; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D000998:Antiviral Agents; D006451:Hemoglobin, Sickle; D014633:Valine; D000077483:Valacyclovir; D015774:Ganciclovir; D010100:Oxygen; D000212:Acyclovir