title: Inhibition of the cellular function of perforin by 1-amino-2,4-dicyanopyrido[1,2-a]benzimidazoles.
abstract: A high throughput screen showed the ability of a 1-amino-2,4-dicyanopyrido[1,2-a]benzimidazole analogue to directly inhibit the lytic activity of the pore-forming protein perforin. A series of analogues were prepared to study structure-activity relationships (SAR) for the this activity, either directly added to cells or released in situ by KHYG-1 NK cells, at non-toxic concentrations. These studies showed that the pyridobenzimidazole moiety was required for effective activity, with strongly basic centres disfavoured. This class of compounds was relatively unaffected by the addition of serum, which was not the case for a previous class of direct inhibitors.
authors.affiliation: Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
authors.forename: Dani M
authors.initials: DM
authors.lastname: Lyons
authors.forename: Kristiina M
authors.initials: KM
authors.lastname: Huttunen
authors.forename: Kylie A
authors.initials: KA
authors.lastname: Browne
authors.forename: Annette
authors.initials: A
authors.lastname: Ciccone
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Trapani
authors.forename: William A
authors.initials: WA
authors.lastname: Denny
authors.forename: Julie A
authors.initials: JA
authors.lastname: Spicer
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects; D054353:Perforin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D054353:Perforin; C031000:benzimidazole