DNA Binding Affinity Assessment of Xanthene Compounds: In Vitro and In Silico Approach

Abstract

Xanthene derivatives are an important class of heterocyclic compounds with a wide spectrum of pharmacological activities. In our previous investigations, we found the good antiproliferative activity of two xanthene derivatives, with minimal toxicity investigated by in vitro tests. In this study, we tested the interaction of compound 1 (powerful potent antiproliferative compound) with calf thymus DNA (CT-DNA) under physiological conditions by spectrophotometric titration. The probable prediction of binding and the type of interaction forces involved in the arrangement between xanthen derivatives and CT-DNA were explored also through molecular docking studies. The results indicated that compound 1 interacts with CT-DNA by grove binding. The binding constant was found to be 2.5 x 104 M-1 and indicates the non-covalent binding of compound 1 to CT-DNA. Docking study results proposed possible binding modes, with binding energies of -9.39 and -8.65 kcal/mol for compounds 1 and 2, respectively, which supported previously obtained in vitro results for antiproliferative activity. In addition to experimental investigation, density functional theory (DFT) calculation with B3LYP/6-31G*, B3LYP/6-31G**, and B3LYP/6-31+G* levels of theories was performed on compounds 1 and 2 to obtain optimized geometry, spectroscopic and electronic properties. These studies could help in understanding the mechanisms of toxicity, resistance, side effects of xanthene derivatives, and their binding action mechanism to DNA.

Keywords

• dna binding
• docking
• dft
• xanthene