TY - JOUR

T1 - Selenium-Substituted Monomethine Cyanine Dyes as Selective G-Quadruplex Spectroscopic Probes with Theranostic Potential

AU - Fabijanic, Ivana

AU - Kurutos, Atanas

AU - Paic, Ana Tomasic

AU - Tadic, Vanja

AU - Kamounah, Fadhil S.

AU - Horvat, Lucija

AU - Brozovic, Anamaria

AU - Crnolatac, Ivo

AU - Radic Stojkovic, Marijana

PY - 2023

Y1 - 2023

N2 - The binding interactions of six ligands, neutral and monocationic asymmetric monomethine cyanine dyes comprising benzoselenazolyl moiety with duplex DNA and RNA and G-quadruplex structures were evaluated using fluorescence, UV/Vis (thermal melting) and circular dichroism (CD) spectroscopy. The main objective was to assess the impact of different substituents (methyl vs. sulfopropyl vs. thiopropyl/thioethyl) on the nitrogen atom of the benzothiazolyl chromophore on various nucleic acid structures. The monomethine cyanine dyes with methyl substituents showed a 100-fold selectivity for G-quadruplex versus duplex DNA. Study results indicate that cyanines bind with G-quadruplex via end pi-pi stacking interactions and possible additional interactions with nucleobases/phosphate backbone of grooves or loop bases. Cyanine with thioethyl substituent distinguishes duplex DNA and RNA and G-quadruplex structures by distinctly varying ICD signals. Furthermore, cell viability assay reveals the submicromolar activity of cyanines with methyl substituents against all tested human cancer cell lines. Confocal microscopy analysis shows preferential accumulation of cyanines with sulfopropyl and thioethyl substituents in mitochondria and indicates localization of cyanines with methyl in nucleus, particularly nucleolus. This confirms the potential of examined cyanines as theranostic agents, possessing both fluorescent properties and cell viability inhibitory effect.

AB - The binding interactions of six ligands, neutral and monocationic asymmetric monomethine cyanine dyes comprising benzoselenazolyl moiety with duplex DNA and RNA and G-quadruplex structures were evaluated using fluorescence, UV/Vis (thermal melting) and circular dichroism (CD) spectroscopy. The main objective was to assess the impact of different substituents (methyl vs. sulfopropyl vs. thiopropyl/thioethyl) on the nitrogen atom of the benzothiazolyl chromophore on various nucleic acid structures. The monomethine cyanine dyes with methyl substituents showed a 100-fold selectivity for G-quadruplex versus duplex DNA. Study results indicate that cyanines bind with G-quadruplex via end pi-pi stacking interactions and possible additional interactions with nucleobases/phosphate backbone of grooves or loop bases. Cyanine with thioethyl substituent distinguishes duplex DNA and RNA and G-quadruplex structures by distinctly varying ICD signals. Furthermore, cell viability assay reveals the submicromolar activity of cyanines with methyl substituents against all tested human cancer cell lines. Confocal microscopy analysis shows preferential accumulation of cyanines with sulfopropyl and thioethyl substituents in mitochondria and indicates localization of cyanines with methyl in nucleus, particularly nucleolus. This confirms the potential of examined cyanines as theranostic agents, possessing both fluorescent properties and cell viability inhibitory effect.

KW - selenium-substituted cyanine dyes

KW - DNA

KW - RNA interaction

KW - G-quadruplex selective recognition

KW - Induced Circular Dichroism

KW - mitochondrial accumulation

KW - cell viability inhibitory effect

KW - HUMAN TELOMERE

KW - NUCLEIC-ACIDS

KW - CIRCULAR-DICHROISM

KW - SYNTHETIC APPROACH

KW - EQUILIBRIUM

KW - BINDING

KW - INTERCALATION

KW - CONSTANTS

KW - RNA

U2 - 10.3390/biom13010128

DO - 10.3390/biom13010128

M3 - Journal article

C2 - 36671513

VL - 13

JO - Biomolecules

JF - Biomolecules

SN - 2218-273X

IS - 1

M1 - 128

ER -