title: Polyanion inhibitors of HIV and other viruses. 7. Polyanionic compounds and polyzwitterionic compounds derived from cyclodextrins as inhibitors of HIV transmission.
abstract: New polyanionic compounds were obtained from radical addition of thiomalic acid and mercaptopropionic acid onto perallylated cyclodextrins (CDs) under UV irradiation with a catalytic amount of alpha,alpha'-azobis(isobutyronitrile). All these polyanions, bearing 18-48 carboxylate groups, inhibited human immunodeficiency virus type 1 (HIV-1) strain IIIB replication in MT-4 cells at a 50% inhibitory concentration (IC50) of 0.1-2.9 microM, while not being toxic to the host cells at concentrations up to 62 microM. These compounds were also active against a clinical HIV-1 isolate (HE) at >/=4-fold higher concentrations. Only some compounds showed activity against the two HIV-2 strains (ROD and EHO) but at higher concentrations than those required to inhibit HIV-1 (IIIB and HE) replication. In addition, these compounds were not active against the M-tropic HIV-1 strain BaL but were active against simian immunodeficiency virus [SIV (MAC251)]. These compounds were also inhibitory to the replication of human cytomegalovirus at an IC50 of 1-10 microM, but not herpes simplex virus (type 1 and type 2) or other (picorna-, toga-, reo-, orthomyxo-, paramyxo-, bunya-, rhabdo-, and poxvirus) viruses. Radical addition on perallylated CDs of a protected cysteine gave polyzwitterionic compounds. None of these last compounds proved inhibitory to the replication of HIV-1, HIV-2, or any of the other viruses tested.
authors.affiliation: Laboratoire de Chimie Organique Physique, Université Montpellier II, Place E. Bataillon, 34095 Montpellier Cedex 5, France.
authors.forename: A
authors.initials: A
authors.lastname: Leydet
authors.forename: C
authors.initials: C
authors.lastname: Moullet
authors.forename: J P
authors.initials: JP
authors.lastname: Roque
authors.forename: M
authors.initials: M
authors.lastname: Witvrouw
authors.forename: C
authors.initials: C
authors.lastname: Pannecouque
authors.forename: G
authors.initials: G
authors.lastname: Andrei
authors.forename: R
authors.initials: R
authors.lastname: Snoeck
authors.forename: J
authors.initials: J
authors.lastname: Neyts
authors.forename: D
authors.initials: D
authors.lastname: Schols
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D002240:Carbohydrate Sequence; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D002460:Cell Line; D002522:Chlorocebus aethiops; D003505:Cyclodextrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D004267:DNA Viruses / Q000187:drug effects; D004285:Dogs; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification; D015498:HIV-2 / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D012328:RNA Viruses / Q000187:drug effects; D013329:Structure-Activity Relationship; D014466:Ultraviolet Rays; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D002264:Carboxylic Acids; D003505:Cyclodextrins