Antiproliferative benzoindazolequinones as potential cyclooxygenase-2 inhibitors

Aurora Molinari, Alfonso Oliva, Marlene Arismendi-Macuer, Leda Guzmán, Waldo Acevedo, Daniel Aguayo, Raúl Vinet, Arturo San Feliciano

Resultado de la investigación: Article

Resumen

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 (∆Gbin) values for cyclooxygenase-2 (COX-2) than for other cancer-related proteins. The predicted ∆Gbin values of these BIZQs, classified in three series, positively correlated with IC50 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 2a, 2c, 6g, and 6k are the most prominent BIZQs, because they showed better IC50 and ∆Gbin 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.

Idioma originalEnglish
Número de artículo2261
PublicaciónMolecules
Volumen24
N.º12
DOI
EstadoPublished - 18 jun 2019

Huella dactilar

Cyclooxygenase 2 Inhibitors
inhibitors
cancer
Cells
cultured cells
Computer Simulation
Inhibitory Concentration 50
proteins
Cell Line
Neoplasms
Quinones
excretion
MCF-7 Cells
quinones
metabolism
Cyclooxygenase 2
Binding energy
Metabolism
Antineoplastic Agents
Assays

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Citar esto

Molinari, A., Oliva, A., Arismendi-Macuer, M., Guzmán, L., Acevedo, W., Aguayo, D., ... Feliciano, A. S. (2019). Antiproliferative benzoindazolequinones as potential cyclooxygenase-2 inhibitors. Molecules, 24(12), [2261]. https://doi.org/10.3390/molecules24122261
Molinari, Aurora ; Oliva, Alfonso ; Arismendi-Macuer, Marlene ; Guzmán, Leda ; Acevedo, Waldo ; Aguayo, Daniel ; Vinet, Raúl ; Feliciano, Arturo San. / Antiproliferative benzoindazolequinones as potential cyclooxygenase-2 inhibitors. En: Molecules. 2019 ; Vol. 24, N.º 12.
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abstract = "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 (∆Gbin) values for cyclooxygenase-2 (COX-2) than for other cancer-related proteins. The predicted ∆Gbin values of these BIZQs, classified in three series, positively correlated with IC50 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 2a, 2c, 6g, and 6k are the most prominent BIZQs, because they showed better IC50 and ∆Gbin 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.",
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Molinari, A, Oliva, A, Arismendi-Macuer, M, Guzmán, L, Acevedo, W, Aguayo, D, Vinet, R & Feliciano, AS 2019, 'Antiproliferative benzoindazolequinones as potential cyclooxygenase-2 inhibitors', Molecules, vol. 24, n.º 12, 2261. https://doi.org/10.3390/molecules24122261

Antiproliferative benzoindazolequinones as potential cyclooxygenase-2 inhibitors. / Molinari, Aurora; Oliva, Alfonso; Arismendi-Macuer, Marlene; Guzmán, Leda; Acevedo, Waldo; Aguayo, Daniel; Vinet, Raúl; Feliciano, Arturo San.

En: Molecules, Vol. 24, N.º 12, 2261, 18.06.2019.

Resultado de la investigación: Article

TY - JOUR

T1 - Antiproliferative benzoindazolequinones as potential cyclooxygenase-2 inhibitors

AU - Molinari, Aurora

AU - Oliva, Alfonso

AU - Arismendi-Macuer, Marlene

AU - Guzmán, Leda

AU - Acevedo, Waldo

AU - Aguayo, Daniel

AU - Vinet, Raúl

AU - Feliciano, Arturo San

PY - 2019/6/18

Y1 - 2019/6/18

N2 - 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 (∆Gbin) values for cyclooxygenase-2 (COX-2) than for other cancer-related proteins. The predicted ∆Gbin values of these BIZQs, classified in three series, positively correlated with IC50 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 2a, 2c, 6g, and 6k are the most prominent BIZQs, because they showed better IC50 and ∆Gbin 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.

AB - 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 (∆Gbin) values for cyclooxygenase-2 (COX-2) than for other cancer-related proteins. The predicted ∆Gbin values of these BIZQs, classified in three series, positively correlated with IC50 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 2a, 2c, 6g, and 6k are the most prominent BIZQs, because they showed better IC50 and ∆Gbin 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.

KW - 1H-benzo[f]indazole-4,9-diones

KW - Antiproliferative activity

KW - Benzoindazolequinones

KW - COX-2 inhibitors

KW - Docking

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U2 - 10.3390/molecules24122261

DO - 10.3390/molecules24122261

M3 - Article

VL - 24

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 12

M1 - 2261

ER -

Molinari A, Oliva A, Arismendi-Macuer M, Guzmán L, Acevedo W, Aguayo D y otros. Antiproliferative benzoindazolequinones as potential cyclooxygenase-2 inhibitors. Molecules. 2019 jun 18;24(12). 2261. https://doi.org/10.3390/molecules24122261