TY - JOUR
T1 - Synthesis and photocytotoxic activity of [1,2,3]triazolo[4,5-h][1,6]naphthyridines and [1,3]oxazolo[5,4-h][1,6]naphthyridines
AU - Montalbano, Alessandra
AU - Barraja, Paola
AU - Cascioferro, Stella Maria
AU - Parrino, Barbara
AU - Cirrincione, Girolamo
AU - Di Martino, Simona
AU - Carbone, Anna
AU - Spano', Virginia
AU - Diana, Patrizia
AU - Doria, Filippo
AU - Nadai, Matteo
AU - Frasson, Ilaria
AU - Freccero, Mauro
AU - Richter, Sara N.
PY - 2019
Y1 - 2019
N2 - [1,2,3]Triazolo[4,5-h][1,6]naphthyridines and [1,3]oxazolo[5,4-h][1,6]naphthyridines were synthesized with the aim to investigate their photocytotoxic activity. Upon irradiation, oxazolo-naphtapyridines induced light-dependent cell death at nanomolar/low micromolar concentrations (EC50 0.01-6.59 μM). The most photocytotoxic derivative showed very high selectivity and photocytotoxicity indexes (SI = 72-86, PTI>5000), along with a triplet excited state with exceptionally long lifetime (18.0 μs) and high molar absorptivity (29781 ± 180 M-1cm-1 at λmax 315 nm). The light-induced production of ROS promptly induced an unquenchable apoptotic process selectively in tumor cells, with mitochondrial and lysosomal involvement. Altogether, these results demonstrate that the most active compound acts as a promising singlet oxygen sensitizer for biological applications.
AB - [1,2,3]Triazolo[4,5-h][1,6]naphthyridines and [1,3]oxazolo[5,4-h][1,6]naphthyridines were synthesized with the aim to investigate their photocytotoxic activity. Upon irradiation, oxazolo-naphtapyridines induced light-dependent cell death at nanomolar/low micromolar concentrations (EC50 0.01-6.59 μM). The most photocytotoxic derivative showed very high selectivity and photocytotoxicity indexes (SI = 72-86, PTI>5000), along with a triplet excited state with exceptionally long lifetime (18.0 μs) and high molar absorptivity (29781 ± 180 M-1cm-1 at λmax 315 nm). The light-induced production of ROS promptly induced an unquenchable apoptotic process selectively in tumor cells, with mitochondrial and lysosomal involvement. Altogether, these results demonstrate that the most active compound acts as a promising singlet oxygen sensitizer for biological applications.
UR - http://hdl.handle.net/10447/349769
M3 - Article
VL - 162
SP - 176-193-193
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
ER -