New ligand-based approach for the discovery of antitrypanosomal compounds

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 7, 2006, Pages 1898-1904

  Vega, María Celeste ^a   Montero Torres, Alina ^b   Marrero Ponce, Yovani ^b,c   Rolón, Miriam ^a   Gómez Barrio, Alicia ^a   Escario, José Antonio ^a   Arán, Vicente J ^d   Nogal, Juan José ^a   Meneses Marcel, Alfredo ^a   Torrens, Francisco ^c  

^a UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^b CENTRAL UNIVERSITY OF LAS VILLAS   (Cuba)

^c UNIVERSITY OF VALENCIA   (Spain)

^d INSTITUTO DE QUÍMICA MÉDICA   (Spain)

Author keywords

Antitypanosomal compound; LDA model; TOMOCOMD software

Indexed keywords

ACETAZOLAMIDE; ADETURON; ADRENALONE; AMANTADINE; AMINOACRIDINE; ANTITRYPANOSOMAL AGENT; ARECOLINE; ASCARIDOLE; CANRENONE; CARBIMAZOLE; CEFALEXIN; CINROMIDE; CYSTAMINE; FENTANYL; GLISOLAMIDE; GLYCEROL; GLYPROTHIAZOL; HEXACHLOROETHANE; HYDROCHLOROTHIAZIDE; KANAMYCIN A; MINOXIDIL; NIFURTIMOX; SPIRONOLACTONE; STREPTOMYCIN; THIOACETAZONE; THIOURACIL; TIMONACIC; TUBERCIDIN; UNINDEXED DRUG; ZONISAMIDE;

ARTICLE; COMPUTER PROGRAM; CONTROLLED STUDY; CYTOTOXICITY; EVALUATION; LIGAND BINDING; MOLECULAR DYNAMICS; NONHUMAN; PARASITE; PREDICTION; TRYPANOSOMA CRUZI;

ANIMALS; ANTIPROTOZOAL AGENTS; LIGANDS; TRYPANOSOMA;

TRYPANOSOMA CRUZI;

EID: 33144458046     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.12.087     Document Type: Article

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37. m represents the mean OD595 value recorded for medium/control wells.
38. 2. The infected cells were then washed twice with PBS, so removing extracellular trypomastigotes. The drugs were added in triplicate, to give a final volume of 900 μL/well. The plates were incubated for 7 days at 33°C. At this time, 100 μL chlorophenol red-β-d-galactopyranoside (CPRG; Roche, Indianapolis, Ind.) solution (final concentration of 400 μM) in 0.3% Triton X-100 (pH 7.4) was added. After 4 h of incubation at 37°C, the colorimetric reaction was quantified as optical densities (OD) at 595 nm. The amastigote inhibition percentage (%AA) was calculated as follows: %AA = 100 - (OD experimental wells/OD control wells) × 100. Background controls (only NCTC-929 cells) were subtracted from all the values.
39. 4 trypomastigote Y strain of T. cruzi harvested from infected murine cardiac blood. After three days, tail blood was examined for the presence of parasites. Mice were treated, in the in vivo experiment three days postinfection, when positive parasitemia was microscopically detected. Only those mice with positive parasitemia were included in the experiments. All compounds were suspended in carboxymethylcellulose and each animal received 0.25 mL of drug suspension daily by gavage feeding. Mice received a dose of 50 mg/kg. One group of control mice was treated orally with 5 consecutive doses of nifurtimox (50 mg/kg). The groups were checked daily and tail blood level parasitemia was checked between days 7 and 22 postinfection (number of parasites per 10 microscope fields, 40× magnification) to give an indication of the level of infection. Infected mice with the same quantity of parasites were used as controls and received only the vehicle as treatment.