Azaterphenyl diamidines as antileishmanial agents.
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.
Hu
Laixing
L
Department of Chemistry and Center for Biotechnology and Drug Design, Georgia State University, Atlanta, GA 30303, USA.
Arafa
Reem K
RK
Ismail
Mohamed A
MA
Wenzler
Tanja
T
Brun
Reto
R
Munde
Manoj
M
Wilson
W David
WD
Nzimiro
Sandra
S
Samyesudhas
Serene
S
Werbovetz
Karl A
KA
Boykin
David W
DW
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*
D000981:Antiprotozoal Agents; D001372:Aza Compounds; D001550:Benzamidines; D016054:DNA, Protozoan; D013730:Terphenyl Compounds