6533b7ddfe1ef96bd12753e6
RESEARCH PRODUCT
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
Ilaria FrassonStella CascioferroAnna CarbonePatrizia DianaMauro FrecceroFilippo DoriaMatteo NadaiPaola BarrajaSara N. RichterAlessandra MontalbanoVirginia SpanòBarbara ParrinoSimona Di MartinoGirolamo Cirrincionesubject
Pharmaceutical ScienceApoptosisMitochondrionPhotochemiotherapy; Photosensitizing agents; Reactive oxygen species; [123]Triazolo[45-h][16]naphthyridines; [13]oxazolo[54-h][16]naphthyridines; Pharmacology; Drug Discovery; Pharmaceutical Science; Organic Chemistry01 natural sciencesMedicinal chemistry[13]oxazolo[54-h][16]naphthyridinechemistry.chemical_compoundDrug Discovery6]naphthyridineschemistry.chemical_classification0303 health sciencesTumorPhotosensitizing AgentsCell DeathSinglet OxygenSinglet oxygenPhotochemiotherapy; Photosensitizing agents; Reactive oxygen species; [1; 2; 3]Triazolo[4; 5-h][1; 6]naphthyridines; [1; 3]oxazolo[5; 4-h][1; 6]naphthyridines; Apoptosis; Cell Death; Cell Line; Tumor; Humans; Lysosomes; Mitochondria; Naphthyridines; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Singlet OxygenGeneral MedicineLysosomeMitochondriaExcited stateReactive oxygen specie5-h][1HumanProgrammed cell death2NaphthyridinePhotochemiotherapy3]Triazolo[4Cell Line03 medical and health sciences4-h][1Cell Line TumorHumansNaphthyridines030304 developmental biologyPharmacologyReactive oxygen speciesPhotosensitizing agent010405 organic chemistryOrganic ChemistryApoptosi0104 chemical sciences3]oxazolo[5chemistryPhotochemotherapyCell cultureApoptosis[123]Triazolo[45-h][16]naphthyridine[1LysosomesReactive Oxygen SpeciesDerivative (chemistry)description
Abstract [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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-05-31 |