Details

Autor(en) / Beteiligte

• Castillo-Garit, Juan A.
• del Toro-Cortés, Oremia
• Kouznetsov, Vladimir V.
• Puentes, Cristian Ochoa
• Romero Bohórquez, Arnold R.
• Vega, Maria C.
• Rolón, Miriam
• Escario, José A.
• Gómez-Barrio, Alicia
• Marrero-Ponce, Yovani
• Torrens, Francisco
• Abad, Concepción

Titel

Identification In Silico and In Vitro of Novel Trypanosomicidal Drug-Like Compounds

Ist Teil von

• Chemical biology & drug design, 2012-07, Vol.80 (1), p.38-45

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• Atom‐based bilinear indices and linear discriminant analysis are used to discover novel trypanosomicidal compounds. The obtained linear discriminant analysis‐based quantitative structure–activity relationship models, using non‐stochastic and stochastic indices, provide accuracies of 89.02% (85.11%) and 89.60% (88.30%) of the chemicals in the training (test) sets, respectively. Later, both models were applied to the virtual screening of 18 in‐house synthesized compounds to find new pro‐lead antitrypanosomal agents. The in vitro antitrypanosomal activity of this set against epimastigote forms of Trypanosoma cruzi is assayed. Predictions agree with experimental results to a great extent (16/18) of the chemicals. Sixteen compounds show more than 70% of epimastigote inhibition at a concentration 100 μg/mL. In addition, three compounds (CRIS 112, CRIS 140 and CRIS 147) present more than 70% of epimastigote inhibition at a concentration of 10 μg/mL (79.95%, 73.97% and 78.13%, respectively) with low values of cytotoxicity (19.7%, 7.44% and 20.63%, correspondingly).Taking into account all these results, we could say that these three compounds could be optimized in forthcoming works. Even though none of them resulted more active than nifurtimox, the current results constitute a step forward in the search for efficient ways to discover new lead antitrypanosomals. Two LDA‐based QSAR models were developed and validated. A pool of approximately 200 compounds was screened to identify potential antitrypanosomal activity. Eighteen compounds were identifies as antitrypanosomal agents by our models. Sixteen of them shown more than 70% of epimastigote inhibition at a concentration of 100 μg/mL