Articolo in rivista, 2018, ENG, 10.1111/cbdd.13108
Lauria A. , Mingoia F., Garcia-Argaez A. N., Delisi R., Martorana A., Dalla Via L.
STEBICEF, Università di Palermo, Italy; CNR-ISMN UOS Palermo, Italy; Univ Padua. Italy; Fondazione per la Biologia e la Medicina della Rigenerazione T.E.S. Tissue Engineering and Signaling Onlus, Padova, Italy.
Due to the scarce biological profile, the pyrazolo[1,2-a]benzo[1,2,3,4]tetrazine-3-one scaffold (PBT) has been recently explored as promising core for potential anticancer candidates. Several suitably decorated derivatives (PBTs) exhibited antiproliferative activity in the low-micromolar range associated with apoptosis induction and cell cycle arrest on S phase. Herein, we selected the most active derivatives and submitted them to further biological explorations to deepen the mechanism of action. At first, a DNA targeting is approached by means of flow Linear Dichroism experiments so as to evaluate how small planar molecules might interact with DNA, including the interference with the catalytic cycle of topoisomerase II and the influence on the cleavable complex stabilization (poisoning effect). In support of the experimental data, in silico studies have been achieved to better understand the chemical space of the interactions. Interestingly some meaningful structural features, useful for further developments, were found. The 8,9-di-Cl substituted derivative revealed as the most effective in the intercalative process, as well as on the inhibition of catalytic activity of topoisomerase II. Predicted ADME studies confirm that PBTs are promising as potential drug candidates.
Chemical biology & drug design (Print) 91 (2), pp. 463–477
antiproliferative, DNA-interacting, intercalation, linear dichroism, molecular docking, pyrazolo[1,2-a]benzo[1,2,3,4]tetrazin-3-one, topoisomerase II
ID: 391941
Year: 2018
Type: Articolo in rivista
Creation: 2018-09-27 14:34:54.000
Last update: 2021-04-19 11:46:33.000
CNR authors
External links
OAI-PMH: Dublin Core
OAI-PMH: Mods
OAI-PMH: RDF
DOI: 10.1111/cbdd.13108
URL: https://onlinelibrary.wiley.com/doi/full/10.1111/cbdd.13108
External IDs
CNR OAI-PMH: oai:it.cnr:prodotti:391941
DOI: 10.1111/cbdd.13108
ISI Web of Science (WOS): 000422952300012
Scopus: 2-s2.0-85031098022