Arabian Journal of Chemistry (Sep 2023)
Structural modifications and biomedical applications of π-extended, π-fused, and non-fused tetra-substituted imidazole derivatives
Abstract
In this present study, we have designed, synthetized twenty three tetra-substituted-imidazole-based fluorescent dyes that belongs to three different families of π-extended, π-fused, and non-fused tetra-substituted derivatives, to investigate their photophysical and biological properties namely anti-cancer and urease inhibitory activity. The impact of structural variation on photophysical properties, and their association with solvent’s polarity, and proticity were throughly examined by comparing with their analogues of blocked ESIPT functionality. Further, they were studied experimentally by means of absorption and fluorescence spectra monitoring through different solvent systems as well as theoretically by density functional theory/time dependent-density functional theory (DFT/TDDFT) calculations, respectively. For the evaluation of biological properties of imidazole molecules, urease inhibitory activity of the imidazole derivatives against urease protein 4H9M was investigated through docking and in vitro studies. Among the synthesized compounds, AHPI-Br and POMPI-F showed the most effective urease inhibitory activity with IC50 values of 0.0288 ± 0.0034 and 0.0289 ± 0.0025 μM and provided the highest docking scores. Moreover, anti-cancer activity of PHPI-I and PHPI-CI imidazole derivatives was confirmed by cytotoxic, and flurorescene analysis in stomach cancer cell lines (AGS). Our results demonstrated that PHPI-I, PHPI-Cl exhibited significant apoptotic mediated cell death compared to all other imidazole groups in both in vitro and in silico analysis. Our present study concluded that synthesis of imidazole derivatives have ability to inhibit urease enzyme activity and anti-cancer activity in vitro and can act as a potential therapeutic targets and warrants in vivo studies.
