title: Dicationic phenyl-2,2'-bichalcophenes and analogues as antiprotozoal agents.
abstract: A series of phenyl-2,2'-bichalcophene diamidines 1a-h were synthesized from the corresponding dinitriles either via a direct reaction with LiN(TMS)₂, followed by deprotection with ethanolic HCl or through the bis-O-acetoxyamidoxime followed by hydrogenation in acetic acid and EtOH over Pd-C. These diamidines show a wide range of DNA affinities as judged from their ΔT(m) values which are remarkably sensitive to replacement of a furan unit with a thiophene one. These differences are explained in terms of the effect of subtle changes in geometry of the diamidines on binding efficacy. Five of the eight compounds were highly active (below 6 nM IC₅₀) in vitro against Trypanosoma brucei rhodesiense (T. b. r.) and four gave IC₅₀values less than 7 nM against Plasmodium falciparum (P. f.). Only one of the compounds was as effective as reference compounds in the T. b. r. mouse model for the acute phase of African trypanosomiasis.
authors.affiliation: Department of Chemistry, Mansoura University, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Ismail
authors.forename: Serry A El
authors.initials: SA
authors.lastname: Bialy
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Tanja
authors.initials: T
authors.lastname: Wenzler
authors.forename: Rupesh
authors.initials: R
authors.lastname: Nanjunda
authors.forename: W David
authors.initials: WD
authors.lastname: Wilson
authors.forename: David W
authors.initials: DW
authors.lastname: Boykin
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D004195:Disease Models, Animal; D051379:Mice; D010419:Pentamidine / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D010963:Plasmodium falciparum / Q000187:drug effects; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects; D014353:Trypanosomiasis, African / Q000188:drug therapy*
chemical_list: D000981:Antiprotozoal Agents; D010419:Pentamidine