title: Azaterphenyl diamidines as antileishmanial agents.
abstract: Eighteen diamidino azaterphenyls and analogues were evaluated as anti-leishmanials; nine of the compounds gave IC50 values less than 1 microM, five exhibited values less than 0.40 microM, and two gave values less than 0.10 microM in a Leishmania donovani axenic amastigote assay. The activity of the diamidines strongly depends on the ring N-atom location relative to the amidine groups and correlates with DNA affinity. Transmission electron microscopy studies showed a dramatic dilation of the mitochondrion and evidence of disintegration of the kinetoplast of the amastigotes.
authors.affiliation: Department of Chemistry and Center for Biotechnology and Drug Design, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Laixing
authors.initials: L
authors.lastname: Hu
authors.forename: Reem K
authors.initials: RK
authors.lastname: Arafa
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Ismail
authors.forename: Tanja
authors.initials: T
authors.lastname: Wenzler
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Manoj
authors.initials: M
authors.lastname: Munde
authors.forename: W David
authors.initials: WD
authors.lastname: Wilson
authors.forename: Sandra
authors.initials: S
authors.lastname: Nzimiro
authors.forename: Serene
authors.initials: S
authors.lastname: Samyesudhas
authors.forename: Karl A
authors.initials: KA
authors.lastname: Werbovetz
authors.forename: David W
authors.initials: DW
authors.lastname: Boykin
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001550:Benzamidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016054:DNA, Protozoan / Q000378:metabolism; D007893:Leishmania donovani / Q000187:drug effects* / Q000235:genetics / Q000648:ultrastructure; D051381:Rats; D013329:Structure-Activity Relationship; D013730:Terphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D001372:Aza Compounds; D001550:Benzamidines; D016054:DNA, Protozoan; D013730:Terphenyl Compounds