Synthesis, DNA binding, fluorescence measurements and antiparasitic activity of DAPI related diamidines.
A novel series of extended DAPI analogues were prepared by insertion of either a carbon-carbon triple bond (16a-d) or a phenyl group (21a,b and 24) at position-2. The new amidines were evaluated in vitro against both Trypanosoma brucei rhodesiense (T. b. r.) and Plasmodium falciparum (P. f.). Five compounds (16a, 16b, 16d, 21a, 21b) exhibited IC(50) values against T. b. r. of 9nM or less which is two to nine folds more effective than DAPI. The same five compounds exhibited IC(50) values against P. f. of 5.9nM or less which is comparable to that of DAPI. The fluorescence properties of these new molecules were recorded, however; they do not offer any advantage over those of DAPI.
Farahat
Abdelbasset A
AA
Department of Chemistry, Georgia State University, Atlanta, GA 30303, United States.
Kumar
Arvind
A
Say
Martial
M
Barghash
Alaa El-Din M
Ael-D
Goda
Fatma E
FE
Eisa
Hassan M
HM
Wenzler
Tanja
T
Brun
Reto
R
Liu
Yang
Y
Mickelson
Leah
L
Wilson
W David
WD
Boykin
David W
DW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D002478:Cells, Cultured; D016054:DNA, Protozoan / Q000737:chemistry / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D005453:Fluorescence; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D051381:Rats; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects*
D016054:DNA, Protozoan; D007211:Indoles; C007293:DAPI