A novel arylhydrazone derivative as a multifunctional membrane protector

This is the authors' abstract. We don't add key points for this paper.

Arylhydrazones have emerged as promising neuroprotective agents for the treatment of neurodegenerative disorders. Based on our prior in vitro and in vivo studies, N′-(3,4-dihydroxybenzylidene)-5-methoxy-1H-indole-2-carbohydrazide (5MeO34OH) was selected as a lead candidate. In the present study, its interactions with SOPC membranes were characterised using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermal shape fluctuation analysis, and phase-contrast and fluorescence microscopy. Systems were also exposed to moderate fast neutron irradiation. It was found that the compound strongly modulated SOPC bilayer behaviour in both native and irradiated states. DSC, FTIR, bending elasticity measurements, and fluorescence microscopy suggested its consistent interfacial positioning, enabling hydrogen bonding with head-groups and hydrophobic interactions with lipid chains. Notably, 5MeO34OH increased membrane rigidity in a concentration-dependent manner, while FTIR and DSC data indicate acyl chain disorder in the presence of acylhydrazone. This suggested interfacial coupling, rather than chain ordering, as a key mechanism for preserving membrane stability under conditions of ionising radiation, where membrane organisation is compromised. Upon irradiation, 5MeO34OH exhibited a radio-protective activity which may be associated with the recovery of co-operative transitions, interfacial hydration, and increased acyl chain disorder. The reported results identify 5MeO34OH as a multifunctional additive with the potential to enhance membrane stability under both physiological and radiation-induced stress.