Highly selective turn-on red fluorescence probes for visualization of the G-quadruplexes DNA in living cells

Studies on small molecule fluorescent probes for detecting G-quadruplexes DNA have bring about an extensive attention in recent years. In this paper, we designed and synthesized three benzothiazole derivatives named 2a-2c under moderate reaction conditions and investigated their interactions with DNA (single-stranded, duplex, i-motif and G-quadruplex) and distribution in living cell. Three compounds present a large Stokes shift (-90 nm) and a weak red fluorescence emission, and they exhibit a good selectivity and sensitive turn-on fluorescence response for the promoter G-quadruplex DNA (bcl-2, c-myc and c-kit 2) and mitochondria G-quadruplex (KSS). The affinity of 2a and 2b with N-alkyl side chain group to DNA is stronger than that of 2c with an anion group, therefore, they also increase the sta-bility of the G-quadruplex structure. 2b induces the conformational change of both bcl-2 and KSS G-quadruplexes, while all compounds induce the folding of bcl-2 from the coiled structure to the hybrid G-qrudruplex. Three compounds interact with the G-quadruplex DNA mainly by end-stacking mode. Furthermore, MTT assays and confocal fluorescence images show that these compounds can enter the liv-ing HepG2 cells with low cytotoxicity. 2a-2c are mainly located in the mitochondrion and interacted with mitochondria G-quadruplex DNA, while only weak fluorescence can be found in cell nucleus. In a word, 2a-2c can be implied in image of G-quadruplex DNA in living cells. (c) 2021 Published by Elsevier B.V.

Automated summary

Recent studies have shown significant interest in small molecule fluorescent probes for detecting G-quadruplexes DNA. In this paper, three benzothiazole derivatives named 2a-2c were synthesized and studied for their interactions with various forms of DNA and distribution in living cells. These compounds exhibited selective and sensitive turn-on fluorescence responses for G-quadruplex DNA, particularly in the mitochondria, with low cytotoxicity. The compounds showed affinity towards G-quadruplex DNA mainly through end-stacking mode, inducing conformational changes and folding of the DNA structures.