title: Potent and selective inhibition of human immunodeficiency virus (HIV)-1 and HIV-2 replication by a class of bicyclams interacting with a viral uncoating event.
abstract: A series of bicyclams have been shown to be potent and selective inhibitors of human immunodeficiency virus (HIV). The compounds are inhibitory to the replication of various HIV-1 and HIV-2 strains in various human T-cell systems, including peripheral blood lymphocytes, at 0.14-1.4 microM, without being toxic to the host cells at 2.2 mM. The bicyclam JM2763 is active against 3'-azido-3'-deoxythymidine (zidovudine; AZT)-resistant HIV-1 strains and acts additively with AZT. Mechanism of action studies revealed that the bicyclams (i.e., JM2763) interact with an early event of the retrovirus replicative cycle, which could be tentatively identified as a viral uncoating event.
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: N
authors.initials: N
authors.lastname: Yamamoto
authors.forename: R
authors.initials: R
authors.lastname: Pauwels
authors.forename: M
authors.initials: M
authors.lastname: Baba
authors.forename: D
authors.initials: D
authors.lastname: Schols
authors.forename: H
authors.initials: H
authors.lastname: Nakashima
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: Z
authors.initials: Z
authors.lastname: Debyser
authors.forename: B A
authors.initials: BA
authors.lastname: Murrer
authors.forename: D
authors.initials: D
authors.lastname: Schwartz
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D015498:HIV-2 / Q000187:drug effects / Q000502:physiology*; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D006571:Heterocyclic Compounds; C024560:cyclam; D015215:Zidovudine