3-Hydroxykynurenic acid: Physicochemical properties and fluorescence labeling

Abstract

Quinoline is one of the most important heterocyclic systems in life sciences. Some derivatives are normal metabolites, and others are used as antibacterial, antimalarial, and anticancer agents. In this work, we describe the synthesis, physicochemical properties, and fluorescence features of a new 4-quinolinone fluorophore, 3-hydroxykynurenic acid (3-HOKA). 3-HOKA was obtained by alkoxide-induced rearrangement of ethyl isatinacetate followed by acidification and then alkaline hydrolysis. The fluorescent compound was characterized by NMR, MS, IR, and UV-Vis spectra. 3-HOKA can exist under a keto-enol equilibrium, but the 4-quinolinone form is the predominant tautomer. In PBS (pH = 7.4), the anionic keto form of 3-HOKA showed a maximum absorption at 368 nm, a fluorescence peak at 474 nm, and a fluorescence quantum yield (Φ F): 0.73. 3-HOKA is photostable and is a moderately weak oxygen generator. Viability assays on HeLa cells indicated that 3-HOKA did not induce significative cytotoxic effects. Under UV excitation, a bright blue fluorescence was selectively found in a singular body within the cytoplasm, a labeling pattern that suggests the possible localization of the probe in the centriole or related structures. Therefore, this novel fluorophore represents a promising prototype compound owing to its biocompatibility and potential biological applications.

Using Quinolin-4-Ones as Convenient Common Precursors for a Metal-Free Total Synthesis of Both Dubamine and Graveoline Alkaloids and Diverse Structural Analogues

“…Subsequently, the intramolecular cyclization of chalcones 21, catalyzed by Amberlyst ® -15 [38], afforded the corresponding dihydroquinolin-4-ones 22a-h in 65-94% yields (see Table 1 and Section 3 Materials and Methods). All the starting chalcones 21 were yellow-to-orange solids, whereas their corresponding dihydroquinolin-4-ones 22 were pale yellow-colored compounds exhibiting strong fluorescence under exposure to long-wavelength UV irradiation in both solid-state and solution forms, in agreement with previous studies on these kinds of systems [41][42][43]. This characteristic easily permitted us to follow the reaction progress by TLC, as well as to check the purity of the key compounds 22.…”

Dual-Functionalized Nanoliposomes Achieve a Synergistic Chemo-Phototherapeutic Effect

“…HeLa cells were grown and directly observed at different post-irradiation times (from 0 to 10 days) by differential interference contrast (DIC) microscopy, as previously [ 74 ]. This allows us to see real-time morphological changes such as rounding up of cells, formation of apoptotic bodies, cellular size increase, or cell growth after the different treatments.…”

Tailored Functionalized Magnetic Nanoparticles to Target Breast Cancer Cells Including Cancer Stem-Like Cells

“…The human breast cancer cell line MDA-MB-231 was obtained from American Type Culture Collection (ATCC ® HTB-26TM) and was cultured following the standard protocols for established cell lines [ 53 ]. Primary cells BB3RC79 derived from a patient with triple negative breast cancer were cultured with DMEM/F12 medium (DMEM/Ham’s F12; Thermo Fisher Scientific), supplemented with 10% FBS, 2 mM L-glutamine (Thermo Fisher Scientific), 50 U mL −1 penicillin and 50 μg mL −1 streptomycin and 10 μg mL −1 insulin (Merck), 1 μg mL −1 hydrocortisone (Merck) and 50 ng mL −1 epidermal growth factor receptor (EGFR) (Miltenyi Biotec; Bergisch Gladbach, Germany).…”