title: Antileishmanial bis-arylimidamides: DB766 analogs modified in the linker region and bis-arylimidamide structure-activity relationships.
abstract: Analogs of the lead antileishmanial bis-arylimidamide DB766 were prepared that possess unsymmetrical substitutions on the diphenylfuran linker, and an additional compound was synthesized that contains isopropoxy groups meta to the central furan. These agents all displayed nanomolar in vitro potency against intracellular Leishmania with selectivity indexes >100 compared to J774 macrophages. While the unsymmetrical analogs were toxic to mice when given ip at 30 mg/kg/day, the compound bearing the meta isopropoxy groups was well tolerated by mice and showed activity in a murine model of visceral leishmaniasis when administered ip at 30 mg/kg/day for five days.
authors: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors: Carolyn S
authors: CS
authors: Reid
authors: Abdelbasset A
authors: AA
authors: Farahat
authors: Xiaohua
authors: X
authors: Zhu
authors: Trupti
authors: T
authors: Pandharkar
authors: David W
authors: DW
authors: Boykin
authors: Karl A
authors: KA
authors: Werbovetz
mesh_terms: D000578:Amidines / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D005663:Furans / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D007891:Leishmania / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000188:drug therapy; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D013329:Structure-Activity Relationship
chemical_list: C552046:2,5-bis(2-(2-propoxy)-4-(2-pyridylimino)aminophenyl)furan; D000578:Amidines; D000981:Antiprotozoal Agents; D005663:Furans