1. Design and synthesis of dual functional NBD-fluorophore-incorporated naphthalene diimide derivatives as G-quadruplex ligands.
- Author
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Zhang X, Li Y, Chen Y, Liu Z, Li Z, Wang Z, Wang Y, and Liu M
- Subjects
- Humans, Cell Line, Tumor, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Fluorescent Dyes chemistry, Fluorescent Dyes chemical synthesis, Fluorescent Dyes pharmacology, Ligands, Molecular Docking Simulation, Molecular Structure, Structure-Activity Relationship, Antineoplastic Agents pharmacology, Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Drug Design, G-Quadruplexes drug effects, Imides chemistry, Imides pharmacology, Imides chemical synthesis, Naphthalenes chemistry, Naphthalenes pharmacology, Naphthalenes chemical synthesis
- Abstract
Nitrobenzoxadiazole (NBD)-incorporated naphthalene diimide derivatives were designed and synthesized as candidates of antitumor agents with cytotoxicity against human pancreatic cancer cell MIA PaCa-2. Among these, compounds 1NND and 3NND exhibited fluorescent "turn-off" property toward human telomeric G-quadruplex (G4), which allows the direct measurement of dissociation constant (K
d ) of ligands against G4 by fluorescence titration method. Notably, the compound 1NND not only exhibited great cytotoxic activity against MIA PaCa-2 with a half maximal inhibitory concentration (IC50 ) of 77.9 nM, but also exhibited high affinity against G4 with Kd of 1.72 μM. Furthermore, the target binding properties were investigated by circular dichroism (CD) spectra and further studied by molecular docking methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)- Published
- 2024
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