Efficacy of the diamidine DB75 and its prodrug DB289, against murine models of human African trypanosomiasis

Arylimidamide DB766, a Potential Chemotherapeutic Candidate for Chagas' Disease Treatment

“…Oral administration of DB766 at 100 mg/kg/day showed good efficacy, with reduced circulating and cardiac parasitism, decreased CK and GPT levels, prevention of electric abnormalities induced by the parasite infection, and significantly reduced mouse mortality without major side effects. These data suggest that sufficient quantities of this AIA were absorbed from the mouse gastrointestinal tract, thus effectively delivering DB766 molecules across the gut mucosa, similar to the results reported for the AD prodrug DB289 (32,67,68).…”

Synthesis and Antiprotozoal Activity of N-Alkoxy Analogues of the Trypanocidal Lead Compound 4,4′-Bis(imidazolinylamino)diphenylamine with Improved Human Blood−Brain Barrier Permeability

“…The STIB900 acute mouse model mimics the first stage of the disease. Experiments were performed as previously reported, 16 human BBB R = OH 3-f old increase P e…”

“…These amidoxime prodrugs are metabolized to the amidine active compounds through sequential oxidative Odemethylation by cytochrome P450 isoforms 1A1, 1A2 and 1B1 and cytochrome b5 catalyzed reductive N-dehydroxylation reactions. [11][12][13][14][15][16][17][18][19][20][21] More recently, similar prodrug strategies (e.g., N-substituted bis-Calkyloxadiazolones, 22 N,N'-dihydroxyamidines, 23 O-carboxymethylamidoximes, 24 diacetyldiamidoximeester 25 ) for the oral delivery of amidines and guanidines were also reported.…”

Lycopodium clavatum and Lycopodium complanatum subsp. chamaecyparissus ekstrelerinin antiprotozoal aktivitesi ve sitotoksisitesi

“…b. rhodesiense (STIB 900 strain) and melarsoprol were used for the assay. This stock was isolated in 1982 from a human patient in Tanzania and after several mouse passages cloned and adapted to axenic culture conditions [16,17]. Minimum Essential Medium (50 µl) supplemented with 25 mM HEPES, 1g/l additional glucose, 1% MEM nonessential amino acids (100×), 0.2 mM 2-mercaptoethanol, 1mM Na-pyruvate and heat-inactivated horse serum (15%) was added to each well of a 96-well microtiter plate.…”