Histamine derived Schiff bases and corresponding spinaceamines - synthesis, characterization and biological evaluation

Abstract

The synthesis of eight new histamine-based Schiff bases and cyclic derivatives spinaceamines was accomplished by the reaction of corresponding aldehydes and histamine as amine-counterpart in absolute ethanol. Bearing in mind that the presence of the imino group/or spinaceamine core in the organic molecular scaffold could bring prominent pharmaceutical properties, all synthesised compounds have been screened for their antimicrobial activities against a range of different bacterial and fungal strains and antioxidant activity, as well as for interactions with bovine serum albumin (BSA) and DNA molecules. According to the observed MIC values, the best activity for both, fungal and bacterial species, was displayed by the compound 3c bearing histamine and quinoline moieties in the structure, especially for Staphylococcus aureus. Results obtained in the fluorescence quenching experiments have confirmed ability of tested compounds for DNA and BSA binding, while docking simulations revealed the site I of sub-domain IIA of BSA as a location of binding sites of tested compounds, as well as the minor grove and intercalation interactions with quite similar possibilities to be considered as compounds DNA-binding modes. Further, the molecular docking studies also gave insight into binding modes to the targeted enzymes (CYP51, cytochrome P450 and TyRS) related to the antifungal and antibacterial potential of tested compounds. Two compounds were selected, Schiff base 3c and spinaceamine 4d, to assess the stability of compounds under the physiological conditions (UV-vis spectroscopic study) and in silico ADME properties (SwissADME software), where both compounds have shown the stability after 72 hours in selected medium, and a potential as a drug based on their ADME properties.