TY - JOUR
T1 - In Vitro and Computational Studies of Perezone and Perezone Angelate as Potential Anti-Glioblastoma Multiforme Agents
AU - Hernández-Rodríguez, Maricarmen
AU - Mendoza Sánchez, Pablo I.
AU - Martínez, Joel
AU - Macías Pérez, Martha E.
AU - Cruz, Erika Rosales
AU - Żołek, Teresa
AU - Maciejewska, Dorota
AU - Ruvalcaba, René Miranda
AU - Jiménez, Elvia Mera
AU - Nicolás-Vázquez, María I.
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/3/1
Y1 - 2022/3/1
N2 - Glioblastoma multiforme (GBM) represents the most malignant type of astrocytoma, with a life expectancy of two years. It has been shown that Poly (ADP-ribose) polymerase 1 (PARP-1) protein is over-expressed in GBM cells, while its expression in healthy tissue is low. In addition, perezone, a phyto-compound, is a PARP-1 inhibitor with anti-neoplastic activity. As a consequence, in the present study, both in vitro and computational evaluations of perezone and its chemically related compound, perezone angelate, as anti-GBM agents were performed. Hence, the anti-proliferative assay showed that perezone angelate induces higher cytotoxicity in the GBM cell line (U373 IC50 = 6.44 µM) than perezone (U373 IC50 = 51.20 µM) by induction of apoptosis. In addition, perezone angelate showed low cytotoxic activity in rat glial cells (IC50 = 173.66 µM). PARP-1 inhibitory activity (IC50 = 5.25 µM) and oxidative stress induction by perezone angelate were corroborated employing in vitro studies. In the other hand, the performed docking studies allowed explaining the PARP-1 inhibitory activity of perezone angelate, and ADMET studies showed its probability to permeate cell membranes and the blood–brain barrier, which is an essential characteristic of drugs to treat neurological diseases. Finally, it is essential to highlight that the results confirm perezone angelate as a potential anti-GBM agent.
AB - Glioblastoma multiforme (GBM) represents the most malignant type of astrocytoma, with a life expectancy of two years. It has been shown that Poly (ADP-ribose) polymerase 1 (PARP-1) protein is over-expressed in GBM cells, while its expression in healthy tissue is low. In addition, perezone, a phyto-compound, is a PARP-1 inhibitor with anti-neoplastic activity. As a consequence, in the present study, both in vitro and computational evaluations of perezone and its chemically related compound, perezone angelate, as anti-GBM agents were performed. Hence, the anti-proliferative assay showed that perezone angelate induces higher cytotoxicity in the GBM cell line (U373 IC50 = 6.44 µM) than perezone (U373 IC50 = 51.20 µM) by induction of apoptosis. In addition, perezone angelate showed low cytotoxic activity in rat glial cells (IC50 = 173.66 µM). PARP-1 inhibitory activity (IC50 = 5.25 µM) and oxidative stress induction by perezone angelate were corroborated employing in vitro studies. In the other hand, the performed docking studies allowed explaining the PARP-1 inhibitory activity of perezone angelate, and ADMET studies showed its probability to permeate cell membranes and the blood–brain barrier, which is an essential characteristic of drugs to treat neurological diseases. Finally, it is essential to highlight that the results confirm perezone angelate as a potential anti-GBM agent.
KW - Anti-neoplastic activity
KW - Computational studies
KW - Drug-likeness
KW - Glioblas-toma multiforme
KW - Phyto-compounds
UR - http://www.scopus.com/inward/record.url?scp=85125661252&partnerID=8YFLogxK
U2 - 10.3390/molecules27051565
DO - 10.3390/molecules27051565
M3 - Artículo
C2 - 35268667
AN - SCOPUS:85125661252
SN - 1420-3049
VL - 27
JO - Molecules
JF - Molecules
IS - 5
M1 - 1565
ER -