Dibutyltin(IV) Complexes Derived from L-DOPA: Synthesis, Molecular Docking, Cytotoxic and Antifungal Activity
Por:
Castillo E.R.-D., Gómez-García O., Andrade-Pavón D., Villa-Tanaca L., Ramírez-Apan T., Nieto-Camacho A., Gómez E.
Publicada:
1 dic 2018
Resumen:
A series of organotin(IV) complexes was herein prepared and
characterized. A one-pot synthetic strategy afforded reasonable to high
yields, depending on the nature of the ligand. All new complexes were
fully characterized by spectroscopic techniques, consisting of IR, MS
and NMR (H-1, C-13 and Sn-119). The in vitro cytotoxicity tests
demonstrated that the organotin complexes produced a greater inhibition,
versus cisplatin (the positive control), of the growth of six human
cancer cell lines: U-251 (glioblastoma), K-562 (chronic myelogenous
leukemia), HCT-15 (colorectal), MCF-7 (breast), MDA-MB-231 (breast) and
SKLU-1 (non-small cell lung). The potency of this cytotoxic activity
depended on the nature of the substituent bonded to the aromatic ring.
All complexes exhibited excellent IC50 values. The test compounds were
also screened in vitro for their antifungal effect against Candida
glabrata and Candida albicans, showing minimum inhibitory concentration
(MIC) values lower than those obtained for fluconazole. A brine shrimp
bioassay was performed to examine the toxic properties. Molecular
docking studies demonstrated that the organotin(IV) complexes bind at
the active site of topoisomerase I in a similar manner to topotecan,
sharing affinity for certain amino acid side chains (11e535, Arg364 and
Asp533), as well as for similar DNA regions (DA113, DC112 and DT10).
Filiaciones:
Castillo E.R.-D.:
Instituto de Química, Universidad Nacional Autónoma de México (UNAM), Circuito Exterior s/n, CiudadUniversitaria, Ciudad de México, 04510, Mexico
Gómez-García O.:
Departamento de Química Orgánica, Laboratorio de Síntesis deFármacos Heterocíclicos, Escuela Nacional de Ciencias Biológicas-Instituto Politécnico Nacional, Prolongaciónde Carpio y Plan de Ayala S/N, Colonia Santo Tomás 11340, Ciudad de México, Mexico
Andrade-Pavón D.:
Departamentode Microbiología-Laboratorio de Biología Molecular de Bacterias y Levaduras, Escuela Nacional de CienciasBiológicas-Iinstituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala S/N, Colonia Santo Tomás11340, Ciudad de México, Mexico
Villa-Tanaca L.:
Departamentode Microbiología-Laboratorio de Biología Molecular de Bacterias y Levaduras, Escuela Nacional de CienciasBiológicas-Iinstituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala S/N, Colonia Santo Tomás11340, Ciudad de México, Mexico
Ramírez-Apan T.:
Instituto de Química, Universidad Nacional Autónoma de México (UNAM), Circuito Exterior s/n, CiudadUniversitaria, Ciudad de México, 04510, Mexico
Nieto-Camacho A.:
Instituto de Química, Universidad Nacional Autónoma de México (UNAM), Circuito Exterior s/n, CiudadUniversitaria, Ciudad de México, 04510, Mexico
Gómez E.:
Instituto de Química, Universidad Nacional Autónoma de México (UNAM), Circuito Exterior s/n, CiudadUniversitaria, Ciudad de México, 04510, Mexico
|