Alkoxyalkyl Esters of Cidofovir and Cyclic Cidofovir Exhibit Multiple-Log Enhancement of Antiviral Activity against Cytomegalovirus and Herpesvirus Replication In Vitro

摘要: The incidence of cytomegalovirus (CMV) retinitis is declining in AIDS patients but remains a significant clinical problem with organ transplants and bone marrow transplants. Prophylaxis ganciclovir (GCV) or valganciclovir reduces the CMV disease may lead to emergence drug-resistant virus mutations UL97 UL54 gene. It would be useful have other types oral therapy for disease. We synthesized hexadecyloxypropyl octadecyloxyethyl derivatives cyclic cidofovir (cCDV) (CDV) found that these novel analogs had 2.5- 4-log increases antiviral activity against compared activities unmodified CDV cCDV. Multiple-log were noted laboratory strains various isolates including GCV-resistant genes. Preliminary cell studies suggest increase partially explained by much greater penetration analogs. 1-O-Hexadecyloxypropyl-CDV, 1-O-octadecyloxyethyl-CDV, their corresponding cCDV are worthy further preclinical evaluation treatment prevention herpes simplex infections humans.