Biological and thermal studies on imidazoline/dimethyl pentanedioate hybrids connected via a hydrazinylidene linker

This article describes - for the first time - the pharmacological, toxicological, and thermal studies of imidazoline/dimethyl pentanedioate hybrids with a hydrazinylidene linker. All compounds showed significant anticancer activity. Simultaneously, the vast majority of them were characterised by higher activity against tumour cells and lower toxicity towards non-tumour cells than gemcitabine. Moreover, they activated apoptotic caspases in some cancer cell lines. None of compounds caused haemolysis, and some even had a protective effect on erythrocytes. All molecules proved to be safer for zebrafish embryos/larvae than an anticancer drug. Thermal studies were performed using DSC, TG/DTG and TG/FTIR/QMS techniques. The melting temperatures of compounds depended on the type of substituent at the phenyl moiety. The melting process of molecules proceeded with one narrow temperature range, without their thermal decomposition. All compounds were characterised by high thermal stability. Their initial decomposition temperatures depended directly on the substituent at the phenyl moiety and the furnace atmosphere used. The pyrolysis and oxidative decomposition of compounds occurred in two main stages, via a radical mechanism. The favourable pharmacological, toxicological, thermal properties and the discovered degradation pathway - crucial for the evaluation of potential drug candidates in the preclinical phase - may predispose these heterocyclic hydrazones to future pharmaceutical applications.