DNA Interactions and Biological Activity of 2,9-Disubstituted 1,10-Phenanthroline Thiosemicarbazone-Based Ligands and a 4-Phenylthiazole Derivative
Authors
Nicolás Prieto, Álvaro; González Quero, Julia; Barroso, Marta; Gándara Barreiro, Zoila; Gude Rodríguez, LourdesIdentifiers
Permanent link (URI): http://hdl.handle.net/10017/59880DOI: https://doi.org/10.3390/biology13010060
ISSN: 2079-7737
Date
2024-01-20Funders
Ministerio de Ciencia e Innovación
Ministerio de Economía, Industria y Competitividad
Universidad de Alcalá
Comunidad de Madrid
Bibliographic citation
Biology, 2024, v. 13, n. 1 (60), p. 1-21
Keywords
thiosemicarbazones (TSCs)
1,10-phenanthroline
G4 DNA
antitumor agents
DNA interactions
Project
info:eu-repo/grantAgreement/MICINN//PID2019-108251RB-I00/ES/
info:eu-repo/grantAgreement/MINECO//CTQ2015-72625-EXP/ES/
info:eu-repo/grantAgreement/UAH//IUAH22%2FCC-028/ES/
info:eu-repo/grantAgreement/UAH//CCG20%2FCC-026/ES/
info:eu-repo/grantAgreement/UAH//CCG19%2FCC-009/ES/
info:eu-repo/grantAgreement/UAH//UAH-AE-2017-2/ES/
info:eu-repo/grantAgreement/CAM//PEJ-2018-TL%2FSAL-11409/ES/
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/publishedVersion
Rights
© The Authors
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Access rights
info:eu-repo/semantics/openAccess
Abstract
Four 1,10-phenanthroline derivatives (1–4) were synthesized as potential telomeric DNA
binders, three substituted in their chains with thiosemicarbazones (TSCs) and one 4-phenylthiazole
derivative. The compounds were characterized using NMR, HRMS, FTIR-spectroscopy and combustion elemental analysis. Quadruplex and dsDNA interactions were preliminarily studied, especially
for neutral derivative 1, using FRET-based DNA melting assays, equilibrium dialysis (both competitive and non-competitive), circular dichroism and viscosity titrations. The TSC derivatives bind and
stabilize the telomeric Tel22 quadruplex more efficiently than dsDNA, with an estimated 24-fold
selectivity determined through equilibrium dialysis for compound 1. In addition, cytotoxic activity
against various tumor cells (PC-3, DU145, HeLa, MCF-7 and HT29) and two normal cell lines (HFF-1
and RWPE-1) was evaluated. Except for the 4-phenylthiazole derivative, which was inactive, the
compounds showed moderate cytotoxic properties, with the salts displaying lower IC50 values
(30–80 µM), compared to the neutral TSC, except in PC-3 cells (IC50 (1) = 18 µM). However, the
neutral derivative was the only compound that exhibited a modest selectivity in the case of prostate
cells (tumor PC-3 versus healthy RWPE-1). Cell cycle analysis and Annexin V/PI assays revealed that
the compounds can produce cell death by apoptosis, an effect that has proven to be similar to that
demonstrated by other known 1,10-phenanthroline G4 ligands endowed with antitumor properties,
such as PhenDC3 and PhenQE8.
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DNA_Nicolas_Biology_2024.pdf | 3.210Mb |
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