Efficacy of S-adenosylhomocysteine hydrolase inhibitors, D-eritadenine and (S)-DHPA, against the growth of Cryptosporidium parvum in vitro.
D-eritadenine and (S)-DHPA are aliphatic adenosine analogues known to target S-adenosylhomocysteine hydrolase (SAHH) and potent antiviral compounds. In the present study, we demonstrate that these two compounds also display efficacy against recombinant SAHH enzyme of the protozoan parasite Cryptosporidium parvum, as well as inhibition of parasite growth in vitro. Our data confirm that SAHH could serve as a rational drug target in cryptosporidial infection and antiviral adenosine analogues are potential candidates for drug development against cryptosporidiosis.
Ctrnáctá
Vlasta
V
Charles University in Prague and University Hospital Bulovka, First Faculty of Medicine, Department of Infectious and Tropical Diseases, Prague, Czech Republic. ctrnacta@yahoo.com
Fritzler
Jason M
JM
Surinová
Mária
M
Hrdý
Ivan
I
Zhu
Guan
G
Stejskal
Frantisek
F
D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D043383:Adenosylhomocysteinase / Q000037:antagonists & inhibitors*; D016785:Cryptosporidium parvum / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D016053:RNA, Protozoan / Q000032:analysis; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004791:Enzyme Inhibitors; D016053:RNA, Protozoan; D011994:Recombinant Proteins; C100029:eritadenine; C016391:9-(2,3-dihydroxypropyl)adenine; D043383:Adenosylhomocysteinase; D000225:Adenine