Picolylamine-functionalized benz[e]indole squaraine dyes: Synthetic approach, characterization and in vitro efficacy as potential anticancer phototherapeutic agents.

Autor: Lima E; Chemistry Centre of Vila Real (CQ-VR), University of Trás-os-Montes and Alto Douro, Quinta de Prados, 5001-801, Vila Real, Portugal; Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Av. Infante D. Henrique, 6201-506, Covilhã, Portugal., Barroso AG; Chemistry Centre of Vila Real (CQ-VR), University of Trás-os-Montes and Alto Douro, Quinta de Prados, 5001-801, Vila Real, Portugal., Sousa MA; Chemistry Centre of Vila Real (CQ-VR), University of Trás-os-Montes and Alto Douro, Quinta de Prados, 5001-801, Vila Real, Portugal., Ferreira O; Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Av. Infante D. Henrique, 6201-506, Covilhã, Portugal., Boto RE; Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Av. Infante D. Henrique, 6201-506, Covilhã, Portugal., Fernandes JR; Chemistry Centre of Vila Real (CQ-VR), University of Trás-os-Montes and Alto Douro, Quinta de Prados, 5001-801, Vila Real, Portugal., Almeida P; Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Av. Infante D. Henrique, 6201-506, Covilhã, Portugal., Silvestre SM; Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Av. Infante D. Henrique, 6201-506, Covilhã, Portugal; Centre for Neuroscience and Cell Biology (CNC), University of Coimbra, Rua Larga, 3000-517, Coimbra, Portugal. Electronic address: sms@ubi.pt., Santos AO; Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Av. Infante D. Henrique, 6201-506, Covilhã, Portugal. Electronic address: aos@ubi.pt., Reis LV; Chemistry Centre of Vila Real (CQ-VR), University of Trás-os-Montes and Alto Douro, Quinta de Prados, 5001-801, Vila Real, Portugal. Electronic address: lucinda.reis@utad.pt.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2022 Feb 05; Vol. 229, pp. 114071. Date of Electronic Publication: 2021 Dec 25.
DOI: 10.1016/j.ejmech.2021.114071
Abstrakt: Squaraine dyes are a family of compounds known for their relevant photophysical and photochemical properties potentially useful as photosensitizing agents. Since pyridines have been introduced into the skeleton of several families of compounds to enhance their pharmacological activity, and this approach had not yet been performed on squaraines, novel dyes derived from benz[e]indole functionalized with picolyl- and dipicolylamine and N-ethyl and -hexyl chains were designed and synthesized. After being fully characterized, their interaction with human albumin was in vitro and in silico evaluated. Dyes were further assessed for their phototoxicity activity, and the most interesting ones were studied regarding cell localization and induction of morphological cell changes, genotoxicity, apoptosis and cell cycle arrest. The molecules with N-ethyl chains showed the greatest in vitro light-dependent cytotoxic effects, particularly the zwitterionic squaraine dye and the one bearing a single pyridine unit, which also exhibited a more significant interaction with human albumin. Phenotypically, the cells incubated with these squaraines became smaller and rounded after irradiation, the effects varying with the tested concentration. Genotoxic effects were observed even without irradiation, being more evident for the N-ethyl picolylamine-derived dye. The fluorescence emitted by Rhodamine 123 largely coincided with that emitted by the dyes, suggesting that they are found preferentially in mitochondria. After irradiation, an increase in the subG1 population was verified by propidium iodide-staining analysis by flow cytometry, indicative of cell death by apoptosis.
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 © 2021 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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