Version 1
: Received: 14 January 2024 / Approved: 15 January 2024 / Online: 15 January 2024 (07:25:10 CET)
Version 2
: Received: 18 January 2024 / Approved: 18 January 2024 / Online: 18 January 2024 (08:48:07 CET)
Nicolás, Á.; Quero, J.G.; Barroso, M.; Gándara, Z.; Gude, L. DNA Interactions and Biological Activity of 2,9-Disubstituted 1,10-Phenanthroline Thiosemicarbazone-Based Ligands and a 4-Phenylthiazole Derivative. Biology2024, 13, 60.
Nicolás, Á.; Quero, J.G.; Barroso, M.; Gándara, Z.; Gude, L. DNA Interactions and Biological Activity of 2,9-Disubstituted 1,10-Phenanthroline Thiosemicarbazone-Based Ligands and a 4-Phenylthiazole Derivative. Biology 2024, 13, 60.
Nicolás, Á.; Quero, J.G.; Barroso, M.; Gándara, Z.; Gude, L. DNA Interactions and Biological Activity of 2,9-Disubstituted 1,10-Phenanthroline Thiosemicarbazone-Based Ligands and a 4-Phenylthiazole Derivative. Biology2024, 13, 60.
Nicolás, Á.; Quero, J.G.; Barroso, M.; Gándara, Z.; Gude, L. DNA Interactions and Biological Activity of 2,9-Disubstituted 1,10-Phenanthroline Thiosemicarbazone-Based Ligands and a 4-Phenylthiazole Derivative. Biology 2024, 13, 60.
Abstract
Four 1,10-phenanthroline derivatives (1-4) have been synthesized as potential telomeric DNA binders, three substituted in their chains with thiosemicarbazones (TSCs), the neutral compound (1) and two ionic derivatives (PF6¯ and BF4¯ salts, 2 and 3, respectively), and a fourth corresponding to a 4-phenylthiazole derivative (4). Quadruplex and dsDNA interactions have been preliminarily studied, especially for the neutral derivative 1, by 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 by equilibrium dialysis for compound 1. In addition, cytotoxic activity against different tumor cells (PC-3, DU145, HeLa, MCF-7 and HT29), and two non-tumor cell lines (HFF-1 and RWPE-1) has been evaluated. Except for the 4-phenylthiazole derivative, which was inactive, the compounds show moderate cytotoxic properties, with the salts displaying lower IC50 values, compared to the neutral TSC. 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 similar to that demonstrated by other known 1,10-phenanthroline G4 ligands endowed with antitumor properties, such as PhenDC3 or PhenQE8.
Keywords
thiosemicarbazones (TSCs); 1,10-phenanthroline; G4 DNA; antitumor agents; DNA interactions
Subject
Chemistry and Materials Science, Medicinal Chemistry
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Commenter: Lourdes Gude
Commenter's Conflict of Interests: Author