Premium
Identification In Silico and In Vitro of Novel Trypanosomicidal Drug‐Like Compounds
Author(s) -
CastilloGarit Juan A.,
del ToroCortés Oremia,
Kouznetsov Vladimir V.,
Puentes Cristian Ochoa,
Romero Bohórquez Arnold R.,
Vega Maria C.,
Rolón Miriam,
Escario José A.,
GómezBarrio Alicia,
MarreroPonce Yovani,
Torrens Francisco,
Abad Concepción
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2012.01378.x
Subject(s) - nifurtimox , in silico , quantitative structure–activity relationship , computational biology , in vitro , linear discriminant analysis , trypanosoma cruzi , identification (biology) , chemistry , biology , stereochemistry , biochemistry , computer science , artificial intelligence , parasite hosting , botany , world wide web , gene
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.