Browsing by Author "Espinosa-Bustos, C."
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- ItemConvergent synthesis, drug target prediction, and docking studies of new 2,6,9-trisubstituted purine derivatives(2021) Villegas, A.; Satheeshkumar, R.; Ballesteros-Casallas, A.; Paulino, M.; Castro, A.; Espinosa-Bustos, C.; Salas Sanchez, Cristian Osvaldo
- ItemDevelopment of 3D-QSAR and pharmacophoric models to design new anti-Trypanosoma cruzi agents based on 2-aryloxynaphthoquinone scaffold(2022) Paulino, M.; Espinosa-Bustos, C.; Bertrand, J.; Cabezas, D.; Mella, J.; Davila, B.; Cerecetto, H.; Ballesteros-Casallas, A.; Salas, C. O.In this work we have collected a set of 30 trypanosomicidal naphthoquinones and developed pharmacophoric and 3D-QSAR models as tools for the design of new potential anti-Chagasic compounds. Firstly, qualitative information was obtained from SAR and pharmacophoric models identifying some fragments around the 2-aryloxynaphthoquinone scaffold important for the antiparasitic activity. Then, 3D-QSAR CoMFA and CoMSIA models were developed. The models showed adequate statistical parameters where the steric, electrostatic, and hydrophobic features explain the trypanosomicidal effect. Therefore, to validate our models, we carried out the design, synthesis, and biological evaluation on T. cruzi epimastigotes of five new compounds (33a-e). According to CoMFA model, three out of five compounds showed pIC(50) values within one logarithmic unit of deviation. The two compounds that did not fit the predictions were those with high lipophilicity, which agreed with the SAR and pharmacophore models. Docking and molecular dynamic studies were performed on T. cruzi trypanothione reductase, in a proposed binding site for this type of naphthoquinone. Interestingly, 33a-e showed the same interaction pattern as a naphthoquinone inhibitor (2). Finally, predicted drug-likeness properties indicated that 33a-e have optimal oral bioavailability. Thus, this study provides new in silico models for obtaining novel trypanosomicidal compounds.
- ItemPromising 2,6,9-trisubstituted purine derivatives for anticancer compounds: Synthesis, 3D-QSAR, and preliminary biological assays(2020) Salas, C.O.; Zarate, A.M.; Kryštof, V.; Mella, J.; Faundez, M.; Brea, J.; Loza, M.I.; Brito, I.; Hendrychová, D.; Jorda, R.; Cabrera Caballero, Alan Raul; Tapia, R.A.; Espinosa-Bustos, C.
- ItemState of the art of Smo antagonists for cancer therapy: Advances in the target receptor and new ligand structures(2019) Espinosa-Bustos, C.; Mella, J.; Soto-Delgado, J.; Salas Sanchez, Cristian Osvaldo
- ItemUnveiling interactions between DNA and cytotoxic 2-arylpiperidinyl-1,4-naphthoquinone derivatives: A combined electrochemical and computational study(2020) Espinosa-Bustos, C.; Canales, C.; Ramírez, G.; Jaque, P.; Salas Sanchez, Cristian Osvaldo