Antiproliferative Benzoindazolequinones as Potential Cyclooxygenase-2 Inhibitors

Quinones and nitrogen heterocyclic moieties have been recognized as important pharmacophores in the development of antitumor agents. This study aimed to establish whether there was any correlation between the in silico predicted parameters and the in vitro antiproliferative activity of a family of b...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2019-06, Vol.24 (12), p.2261
Main Authors: Molinari, Aurora, Oliva, Alfonso, Arismendi-Macuer, Marlene, Guzmán, Leda, Acevedo, Waldo, Aguayo, Daniel, Vinet, Raúl, San Feliciano, Arturo
Format: Article
Language:English
Subjects:
1H-benzo[f]indazole-4,9-diones
Amino acids
Angiogenesis
antiproliferative activity
Antiproliferatives
benzoindazolequinones
Biological activity
Breast cancer
Cancer therapies
Chemotherapy
COX-2 inhibitors
Cyclooxygenase-2
Cytotoxicity
docking
Drug resistance
Heterogeneity
Inflammation
Kinases
Leukemia
Proteins
Therapeutic applications
Vascular endothelial growth factor
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Summary:Quinones and nitrogen heterocyclic moieties have been recognized as important pharmacophores in the development of antitumor agents. This study aimed to establish whether there was any correlation between the in silico predicted parameters and the in vitro antiproliferative activity of a family of benzoindazolequinones (BIZQs), and to evaluate overexpressed proteins in human cancer cells as potential biomolecular targets of these compounds. For this purpose, this study was carried out using KATO-III and MCF-7 cell lines as in vitro models. Docking results showed that these BIZQs present better binding energies (ΔG ) values for cyclooxygenase-2 (COX-2) than for other cancer-related proteins. The predicted ∆G values of these BIZQs, classified in three series, positively correlated with IC measured in both cell lines (KATO-III: 0.72, 0.41, and 0.90; MCF-7: 0.79, 0.55, and 0.87 for Series I, II, and III, respectively). The results also indicated that compounds , , , and are the most prominent BIZQs, because they showed better IC and ∆G values than the other derivatives. In silico drug absorption, distribution, metabolism, and excretion (ADME) properties of the three series were also analyzed and showed that several BIZQs could be selected as potential candidates for cancer pre-clinical assays.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules24122261