Dithiocarbamate-based novel anti-histaminic agents: synthesis, characterization, crystal structure and thermal study

Abstract

A new N-(4-fluorobenzyl) N-(pyridin-2-ylmethyl) dithiocarbamate ligand (fbpm) having structural similarity to clinically approved antihistaminic drugs (viz. pheniramine, chlorpheniramine, and brompheniramine) and its four metal complexes [Co(fbpm)3] (1), [Ni(fbpm)2] (2), [Cu(fbpm)2] (3), and [Zn(fbpm)2] (4) were successfully synthesized and characterized by various techniques i.e. elemental analysis, FT-IR spectroscopy, HR-MS, NMR spectroscopy, and absorption and emission spectroscopy. Furthermore, complexes 1 and 2 were characterized by single crystal X-ray diffraction. Complex 1 adopts distorted octahedral geometry around the Co(iii) center while complex 2 adopts distorted square planar geometry around the Zn(ii) center. X-ray data also showed various weak intermolecular C-H⋯F and C-H⋯N hydrogen bonding interactions leading to supramolecular architectures in complexes 1 and 2. The thermal decomposition study of complexes 1-4 analyzed by TGA shows that they are thermally stable up to 150 °C and also gives strong evidence for the formation of respective metal sulfides at higher temperatures. The antihistaminic activity of the ligand (fbpm) and its complexes 1-4 was examined against clonidine and haloperidol-induced catalepsy in Swiss albino mice of either gender in an in vivo animal model. The result shows that these synthesized compounds have antihistaminic potential to inhibit clonidine-induced catalepsy and may be targeted for different allergic conditions. Complex 3 showed maximum reduction in clonidine-induced catalepsy after 180 minutes of treatment when compared with the induced control. © 2024 The Royal Society of Chemistry.