Polycationic Monomeric and Homodimeric Asymmetric Monomethine Cyanine Dyes with Hydroxypropyl Functionality-Strong Affinity Nucleic Acids Binders.

Ivana Mikulin,Ivo Piantanida,Lidija Uzelac,Meglena Kandinska,Aleksey Vasilev,Irena Martin-Kleiner,Marijeta Kralj,Ivana Ljubić,Mihail Mondeshki,Lidija-Marija Tumir

doi:10.3390/biom11081075

Ivana Mikulin, Ivo Piantanida + Show 8 more

Open Access

https://doi.org/10.3390/biom11081075

Copy DOI

Abstract

New analogs of the commercial asymmetric monomethine cyanine dyes thiazole orange (TO) and thiazole orange homodimer (TOTO) with hydroxypropyl functionality were synthesized and their properties in the presence of different nucleic acids were studied. The novel compounds showed strong, micromolar and submicromolar affinities to all examined DNA ds-polynucleotides and poly rA–poly rU. The compounds studied showed selectivity towards GC-DNA base pairs over AT-DNA, which included both binding affinity and a strong fluorescence response. CD titrations showed aggregation along the polynucleotide with well-defined supramolecular chirality. The single dipyridinium-bridged dimer showed intercalation at low dye-DNA/RNA ratios. All new cyanine dyes showed potent micromolar antiproliferative activity against cancer cell lines, making them promising theranostic agents.

Highlights

The binding of small molecules to DNA/RNA was of scientific interest for decades because of the enormous biological significance of polynucleotides
New cyanine dyes were synthesized according to previously published procedures and quaternized to afford the monomer and dimer water-soluble dyes
Analogues of the thiazole orange (TO) and TOTO dye were substituted by the hydroxypropyl on benzothiazole group instead of methyl, while cyanine units were linked by polypropylene-ammonium, dipyridinium or the dipiperidinium bridge

Summary

Introduction

The binding of small molecules to DNA/RNA was of scientific interest for decades because of the enormous biological significance of polynucleotides. Formation of the supramolecular complex of small molecule–DNA/RNA could influence processes in the living cell, like DNA replication, transcription to RNA and protein synthesis [1,2,3]. A small molecule is bound to a double-stranded (ds) polynucleotide by intercalation between base pairs, minor or major groove binding and/or external electrostatic binding [5]. There is a challenging task to design and synthesize a small molecule capable of strong binding combined with specific recognition of a certain structure type (e.g., AT-rich sequence or GC-rich sequence, DNA or RNA, single-stranded or double-stranded helix, a different type of helix, like A, B, Z, etc.) and a specific binding response [6,7].

Objectives

Methods

Results

Discussion

Conclusion