Synthesis and antiprotozoal properties of pentamidine congeners bearing the benzofuran motif.
Forty-eight cationically substituted pentamidine congeners possessing benzofuran rings were synthesized by a copper mediated heteroannulation of substituted o-iodophenols with phenyl acetylenes. Activities of compounds 1-48 against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani and cytotoxicities for mammalian cells were influenced by the nature of cationic substituents, placement of the benzofuran fragment, and the length of the carbon linker between aromatic moieties. Several dications exhibited superior antiplasmodial and antileishmanial potencies compared to pentamidine.
Bakunov
Stanislav A
SA
Department of Pathology and Laboratory Medicine, School of Medicine, The University of North Carolina, Chapel Hill, North Carolina 27599-7525, USA.
Bakunova
Svetlana M
SM
Bridges
Arlene S
AS
Wenzler
Tanja
T
Barszcz
Todd
T
Werbovetz
Karl A
KA
Brun
Reto
R
Tidwell
Richard R
RR
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D001572:Benzofurans / Q000737:chemistry*; D002460:Cell Line; D007893:Leishmania donovani / Q000187:drug effects; D010419:Pentamidine / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D010963:Plasmodium falciparum / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects
D000981:Antiprotozoal Agents; D001572:Benzofurans; D010419:Pentamidine; C105430:benzofuran