Thioflavin T (ThT) is a well-established fluorescence probe with selectivity for G-quadruplex (G4) structures. Over the past few years, G4 ligands have emerged as promising candidates for the development of antiparasitic agents. Building on this concept, we explored extending ThT’s benzothiazole scaffold by introducing various 2-ethenyl aromatic and heteroaromatic moieties, aiming to enhance G4 binding affinity and potential therapeutic effect. A series of benzothiazolium derivatives were synthesized and evaluated for their antiproliferative and antiparasitic activity. Several 2-ethenyl benzothiazole derivatives showed submicromolar activity against Leishmania spp. and Trypanosoma brucei parasites, with up to 200-fold selectivity over MRC-5 human lung fibroblasts. Notably, compound 2b demonstrated remarkable potency, with an IC50 of 0.48 nM and a selectivity index of 46,151 against Leishmania major amastigotes, and an IC50 of 0.019 nM and a selectivity index of 79,206 against T. brucei. In fact, compound 2b demonstrated superior efficacy and selectivity in comparison to the clinically used drugs suramin, fexinidazole, miltefosine, and amphotericin B. Biophysical studies revealed that all tested derivatives exhibited significant G4 stabilization, surpassing ThT. Location of compound 2b inside the nucleus and the kinetoplast, as well as partially in the mitochondria, opens up the possibility of 2b acting against the parasite through binding to G4.

The ability to selectively control DNA conformation using light as an external stimulus offers unique opportunities to control specific DNA sequences in biological settings and to develop nucleotide-b...

Carbon-based functional nanomaterials with distinct photoluminescent properties have gained significant attention for their diverse applications in bioimaging, biomedicine, and antimicrobial treatment...

Carbon-based functional nanomaterials with distinct photoluminescent properties have gained significant attention for their diverse applications in bioimaging, biomedicine, and antimicrobial treatment...

Sialic acids (Sias), consisting primarily of N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), play crucial roles in many biological processes. The detection and quantification of Sias are essential for understanding their roles in health and disease progression. Although numerous techniques have been developed to enhance the specificity and sensitivity of Sias analysis, traditional methods such as derivatization with fluorescent tags coupled with HPLC-MS analysis often suffer from low limits of detection, limiting the quantification of Sias in trace samples. Here, we introduce DAPMI, a novel imidazolium-based ITag for sensitive Sia detection. We demonstrate its utility in the detection and quantification of Sia composition in human serum, and in different tissues from CMAH (cytidine monophosphate-N-acetylneuraminic acid hydroxylase) knockout mice, using ESI-MS analysis and with a limit of detection (LOD) down to the low fmol range. The results showed that both Neu5Ac and Neu5Gc were present in varying proportions in wild-type mice and CMAH heterogeneous mice. Trace amounts of Neu5Gc were also detected in the tissues of CMAH null homogeneous mice (CMAH–/−) and in human blood serum using ESI-ToF-MS, suggesting its presence may be linked to dietary intake of Neu5Gc-containing foods, as Neu5Gc cannot be synthesized endogenously in CMAH–/– mice, and in humans. The DAPMI-ITag and the labeling technology developed in this study significantly improve the sensitivity of Sias detection compared to conventional tags such as o-phenylenediamine (OPD), and provide a new chemical tool for the exploration of Sias’ biological roles and their use as biomarkers in different human conditions.