Structure-activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH.
Cryptosporidium parasites are important waterborne pathogens of both humans and animals. The Cryptosporidium parvum and Cryptosporidium hominis genomes indicate that the only route to guanine nucleotides is via inosine 5'-monophosphate dehydrogenase (IMPDH). Thus the inhibition of the parasite IMPDH presents a potential strategy for treating Cryptosporidium infections. A selective benzimidazole-based inhibitor of C. parvum IMPDH (CpIMPDH) was previously identified in a high throughput screen. Here we report a structure-activity relationship study of benzimidazole-based compounds that resulted in potent and selective inhibitors of CpIMPDH. Several compounds display potent antiparasitic activity in vitro.
Department of Biology, Brandeis University, MS009, 415 South Street, Waltham, MA 02454, USA.
Sivapriya
S
Kirubakaran
Suresh Kumar
SK
Gorla
Lisa
L
Sharling
Minjia
M
Zhang
Xiaoping
X
Liu
Soumya S
SS
Ray
Iain S
IS
Macpherson
Boris
B
Striepen
Lizbeth
L
Hedstrom
Gregory D
GD
Cuny
D000818:Animals; D000977:Antiparasitic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003457:Cryptosporidiosis / Q000188:drug therapy; D016785:Cryptosporidium parvum / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000977:Antiparasitic Agents; D001562:Benzimidazoles; D007168:IMP Dehydrogenase