Multicomponent synthesis of benzo[c]acridinones, physicochemical analysis of their inclusion complexes with cyclodextrins in the liquid state, and evaluation of the inhibition of enzymatic activity

Abstract

Benzo[c]acridinones are heterocyclic compounds with promising biological potential, including antimicrobial and antitumor effects. However, these molecules are nonpolar and exhibit low solubility, limiting their practical application. To overcome this limitation, the formation of inclusion complexes has been investigated as a strategy to enhance solubility. Among potential complexing agents, cyclodextrins stand out due to their widespread use in the pharmaceutical industry. This study aimed to investigate the formation of inclusion complexes in solution through spectroscopic analyses, including ultraviolet-visible (UV-vis) spectroscopy and one- and two-dimensional nuclear magnetic resonance (NMR). The results demonstrated the efficiency of various cyclodextrins in forming soluble inclusion complexes. It was observed that the interaction between cyclodextrins and benzo[c]acridinones is primarily governed by weak intermolecular forces. Two-dimensional NMR (ROESY) confirmed the formation of inclusion complexes between the C2 molecule and β-cyclodextrin (β-CD), while no inclusion complex was observed for the C1 molecule. Additionally, in vitro dissolution studies indicated an increase in the solubility of the molecules upon complexation. The ability of these compounds and their inclusion complexes to inhibit phospholipase A₂ and protease enzymes was also evaluated. The results showed that the inclusion complexes exhibited enhanced inhibitory activity compared to the pure compounds.