Structural basis of multi-target interactions of Henna Dye Lawsone: an experimental and theoretical evaluation

Lawsone (2-hydroxy-1,4-naphthoquinone), also known as hennotannic acid, is a red-orange dye present in the leaves of the henna plant (<i>Lawsonia inermis</i>) having lots of biological activities. In this paper, we have investigated the structural basis of binding affinities of Lawsone towards two different targets namely, calf thymus DNA (CT-DNA) and protein bovine serum albumin (BSA) using experimental and computational approaches. This phytochemical binds to the minor groove of DNA and Sudlow site II, Domain III of BSA. The binding constants obtained from spectroscopic studies for Lawsone with DNA and BSA have been determined as 1.79 × 10³ M^-1 and 2.18 × 10³ M^-1, respectively with corresponding Gibbs free energies of -4.46 kcal/mol and -4.58 kcal/mol. Conformational changes in the secondary structures of the receptors upon binding with Lawsone is observed. Isothermal titration calorimetry (ITC) experiments reveal that binding is favoured mainly due to negative enthalpy changes (-18.2 kcal/mol for DNA and -98.77 kcal/mol for BSA). Molecular docking and dynamics simulations elucidate intermolecular contacts between Lawsone and the receptors, providing insight into the energetic profile of the complexes and revealing Lawsone's reorientation within the binding sites. Both experimental and computational findings highlight the significance of hydrogen bonding and hydrophobic interactions in the binding process, offering valuable insights into Lawsone's molecular interactions with biomolecules and its potential therapeutic applications.