Inclusion complexes of novel formyl chromone Schiff bases with β-Cyclodextrin: Synthesis, characterization, DNA binding studies and in-vitro release study

The present study involved the synthesis of five novel Schiff bases (SB1-SB5) of formyl chromone and their inclusion complexes with beta-cyclodextrin through kneading approach to enhance the solubility and stability of SBs. Characterization was conducted using FTIR, NMR, SEM, TEM, p-XRD, and Mass Spectrometry. UV fluorescence and pH stability studies confirmed the formation of the inclusion complex. Structural validation of complexes was conducted via molecular docking (PDB ID: 1BFN) and 50 ns MD simulation study. DFT studies were performed on SBs using B3LYP/6-31 + G(d,p) basis set. All SBs exhibited favorable ADME properties and high binding interactions were observed in molecular docking with ctDNA (PDB Id: 1BNA). Further, in-vitro UV absorption and fluorescence experiments demonstrated strong ctDNA interactions for all Schiff bases, with binding constants in the order of 10(5) M-1, indicating groove binding mode. Among the SBs, SB4 exhibited the highest affinity for DNA grooves, with a binding constant (K-b) of 1.7 x 10(6) M-1. However, the SB4/beta-Cyd inclusion complex also interacted with DNA but with low binding constants compared to SB4. An in-vitro release study of SB4/beta-Cyd, revealed 78.92 % dissolution of the inclusion complex, highlighting its potential for enhanced solubility and stability in biological systems.