Fluorinated rhodacyanine (SJL-01) possessing high efficacy for visceral leishmaniasis (VL).
Anti-Leishmania in vitro and in vivo activities of various rhodacyanine derivatives have been examined. Among them, the fluorinatied variant SJL-01 (8) showed IC(50) of 0.011 microM against Leishmania donovani strain MHOM/ET/67/L82 (selective index of >15000) and 95-97% inhibition against L. donovani strain MHOM/ET/67/HU in female BALB/c mice by 1.3-12.5 mg/kg x 5 iv administrations. Negative results on chromosomal aberration test and in vitro micronucleus test suggest that compound 8 is a hopeful candidate for visceral leishmaniasis (VL).
Yang
Mei
M
Drug Discovery Science Research Center, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
Arai
Chika
C
Bakar Md
Abu
A
Lu
Jun
J
Ge
Jian-Feng
JF
Pudhom
Khanitha
K
Takasu
Kiyosei
K
Kasai
Kazuki
K
Kaiser
Marcel
M
Brun
Reto
R
Yardley
Vanessa
V
Itoh
Isamu
I
Ihara
Masataka
M
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D052160:Benzothiazoles / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D007893:Leishmania donovani / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D021261:Parasitic Sensitivity Tests; D051381:Rats
C546800:2-((3-ethyl-5-(2-(3-methylbenzo(d)thiazol-2(3H)-ylidene)ethylidene)-4-oxothiazolidin-2-ylidene)methyl)-5-fluoro-3-methylbenzo(d)thiazol-3-ium; D000981:Antiprotozoal Agents; D052160:Benzothiazoles