José Eduardo Cadena-Cruz1, Luis M Guamán-Ortiz2, Juan Carlos Romero-Benavides3, Natalia Bailon-Moscoso2, Kevin E Murillo-Sotomayor2, Nadia V Ortiz-Guamán2, Jorge Heredia-Moya4. 1. Facultad de Ciencias Químicas, Universidad Central del Ecuador, Quito, Ecuador. 2. Departamento de Ciencias de La Salud, Universidad Técnica Particular de Loja, San Cayetano Alto s/n, C.P. 11 01 608, Loja, Ecuador. 3. Departamento de Química y Ciencias Exactas, Universidad Técnica Particular de Loja, San Cayetano Alto s/n, C.P. 11 01 608, Loja, Ecuador. 4. Centro de Investigación Biomédica (CENBIO), Facultad de Ciencias de la Salud Eugenio Espejo, Universidad UTE, 170527, Quito, Ecuador. jorgeh.heredia@ute.edu.ec.
Abstract
BACKGROUND: Pyrazoles have attracted particular attention due to the diverse biological activities associated with this heterocyclic system, and some have been shown to be cytotoxic to several human cell lines. Several drugs currently on the market have this heterocycle as the key structural motif, and some have been approved for the treatment of different types of cancer. RESULTS: 4,4'-(Arylmethylene)bis(1H-pyrazol-5-ols) derivatives 3a-q were synthetized by a three components reaction of 3-methyl-1-phenyl-5-pyrazolone (1) with various benzaldehydes 2 catalyzed by sodium acetate at room temperature. The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR) and were evaluated for their radical scavenging activity by DPPH assay and tested in vitro on colorectal RKO carcinoma cells in order to determine their cytotoxic properties. All 4,4'-(arylmethylene)bis(1H-pyrazol-5-ols) derivatives 3a-q were synthetized in high to excellent yield, and pure products were isolated by simple filtration. All compounds have good radical scavenging activity, and half of them are more active than ascorbic acid used as standard. CONCLUSION: Several derivatives proved to be cytotoxic in the RKO cell line. In particular, compound 3i proved to be a very potent scavenger with an IC50 of 6.2 ± 0.6 µM and exhibited an IC50 of 9.9 ± 1.1 μM against RKO cell. Autophagy proteins were activated as a survival mechanism, whereas the predominant pathway of death was p53-mediated apoptosis.
BACKGROUND:Pyrazoles have attracted particular attention due to the diverse biological activities associated with this heterocyclic system, and some have been shown to be cytotoxic to several human cell lines. Several drugs currently on the market have this heterocycle as the key structural motif, and some have been approved for the treatment of different types of cancer. RESULTS:4,4'-(Arylmethylene)bis(1H-pyrazol-5-ols) derivatives 3a-q were synthetized by a three components reaction of 3-methyl-1-phenyl-5-pyrazolone (1) with various benzaldehydes 2 catalyzed by sodium acetate at room temperature. The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR) and were evaluated for their radical scavenging activity by DPPH assay and tested in vitro on colorectal RKO carcinoma cells in order to determine their cytotoxic properties. All 4,4'-(arylmethylene)bis(1H-pyrazol-5-ols) derivatives 3a-q were synthetized in high to excellent yield, and pure products were isolated by simple filtration. All compounds have good radical scavenging activity, and half of them are more active than ascorbic acid used as standard. CONCLUSION: Several derivatives proved to be cytotoxic in the RKO cell line. In particular, compound 3i proved to be a very potent scavenger with an IC50 of 6.2 ± 0.6 µM and exhibited an IC50 of 9.9 ± 1.1 μM against RKO cell. Autophagy proteins were activated as a survival mechanism, whereas the predominant pathway of death was p53-mediated apoptosis.
Authors: Mervat S Mohamed; Abdou O Abdelhamid; Fahad M Almutairi; Ayat G Ali; Mai K Bishr Journal: Bioorg Med Chem Date: 2017-12-20 Impact factor: 3.641
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Authors: Rosivaldo S Borges; Auriekson N Queiroz; Anna P S Mendes; Sanderson C Araújo; Luiz C S França; Edna C S Franco; Walace G Leal; Albérico B F Da Silva Journal: Int J Mol Sci Date: 2012-06-20 Impact factor: 6.208