Design, Synthesis, Spectroscopic Characterisation and In Vitro Cytostatic Evaluation of Novel Bis(coumarin-1,2,3-triazolyl)benzenes and Hybrid Coumarin-1,2,3-triazolyl-aryl Derivatives

In this work, a series of novel 1, 2, 3-triazolyl-coumarin hybrid systems were designed as potential antitumour agents. The structural modification of the coumarin ring was carried out by Cu(I)-catalysed Huisgen 1, 3-dipolar cycloaddition of 7-azido-4-methylcoumarin and terminal aromatic alkynes to obtain 1, 4-disubstituted 1, 2, 3-triazolyl-coumarin conjugates 2a–g, bis(1, 2, 3-triazolyl-coumarin)benzenes 2h–i and coumarin-1, 2, 3-triazolyl-benzazole hybrids 4a–b. The newly synthesised hybrid molecules were investigated for in vitro antitumour activity against five human cancer cell lines, colon carcinoma HCT116, breast carcinoma MCF-7, lung carcinoma H 460, human T-lymphocyte cells CEM, cervix carcinoma cells HeLa, as well as human dermal microvascular endothelial cells (HMEC-1). Most of these compounds showed moderate to pronounced cytotoxic activity, especially towards MCF-7 cell lines with IC50 = 0.3–32 μM. In addition, compounds 2a–i and 4a–b were studied by UV-Vis absorption and fluorescence spectroscopy and their basic photophysical parameters were determined

Naphthalimide-Piperazine Derivatives as Multifunctional “On” and “Off” Fluorescent Switches for pH, Hg²⁺ and Cu²⁺ Ions

Novel 1,8-naphthalimide-based fluorescent probes NI-1 and NI-2 were designed and screened for use as chemosensors for detection of heavy metal ions. Two moieties, methylpyridine (NI-1) and hydroxyphenyl (NI-2), were attached via piperazine at the C-4 position of the napthalimide core resulting in a notable effect on their spectroscopic properties. NI-1 and NI-2 are pH sensitive and show an increase in fluorescence intensity at around 525 nm (switch “on”) in the acidic environment, with pKa values at 4.98 and 2.91, respectively. Amongst heavy metal ions only Cu2+ and Hg2+ had a significant effect on the spectroscopic properties. The fluorescence of NI-1 is quenched in the presence of either Cu2+ or Hg2+ which is attributed to the formation of 1:1 metal-ligand complexes with binding constants of 3.6 × 105 and 3.9 × 104, respectively. The NI-1 chemosensor can be used for the quantification of Cu2+ ions in sub-micromolar quantities, with a linear range from 250 nM to 4.0 μM and a detection limit of 1.5 × 10−8 M. The linear range for the determination of Hg2+ is from 2 μM to 10 μM, with a detection limit of 8.8 × 10−8 M. Conversely, NI-2 behaves like a typical photoinduced electron transfer (PET) sensor for Hg2+ ions. Here, the formation of a complex with Hg2+ (binding constant 8.3 × 103) turns the green fluorescence of NI-2 into the “on” state. NI-2 showed remarkable selectivity towards Hg2+ ions, allowing for determination of Hg2+ concentration over a linear range of 1.3 μM to 25 μM and a limit of detection of 4.1 × 10−7 M