Evaluation of new thiazolide/thiadiazolide derivatives reveals nitro group-independent efficacy against in vitro development of Cryptosporidium parvum.
Thirty-nine new thiazolide/thiadiazolide compounds were compared with the nitrothiazole nitazoxanide for activity against Cryptosporidium parvum development in HCT-8 cells. Twenty-seven agents exerted > or =90% inhibition. Agents with a lower 50% inhibitory concentration (IC(50)) than nitazoxanide were either NO(2) or halogen 5 substituted on the thiazole moiety. Other 5 substitutions such as methyl, C(3)H(7), C(6)H(11), H, SO(2)CH(3), and SCH(3) negatively impacted activity. Five-substituted deacetylated analogues exhibited higher IC(50)s than their acetylated counterparts. Halogeno-thiazolide/thiadiazolides may provide valuable nitro-free alternatives to nitazoxanide.
Gargala
Gilles
G
Parasitology Department, Rouen University Hospital and UPRES-EA 4311-IFRMP 23, University of Rouen, Rouen, France. gilles.gargala@univ-rouen.fr
Le Goff
Laetitia
L
Ballet
Jean-Jacques
JJ
Favennec
Loic
L
Stachulski
Andrew V
AV
Rossignol
Jean-François
JF
D000981:Antiprotozoal Agents / Q000494:pharmacology; D016785:Cryptosporidium parvum / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D020128:Inhibitory Concentration 50; D009574:Nitro Compounds; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship; D013829:Thiadiazines / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
D000981:Antiprotozoal Agents; D009574:Nitro Compounds; D013829:Thiadiazines; D013844:Thiazoles; C041747:nitazoxanide