Charge density and electrostatic potential of hepatitis C anti-viral agent andrographolide: an experimental and theoretical study

Abstract

Andrographolide (AGH) is a hepatitis C anti-viral agent which targets the host cell by covalently binding with the NF-κBreceptor. The experimental electron density distribution study of AGH has been carried out from high-resolution X-ray diffraction data collected at 110.2 (3) K. The unit-cell packing of AGH was stabilized by strong O—H...O and weak C—H...O types of intermolecular interactions. The dissociation energy of the strong hydrogen bond O2—H22...O1 is very high, 32 kJ mol−1. The percentage occupancy of H...H interactions is found to be maximum (68.5%) when it comparing with the other types of interactions occurring in the AGH crystalline phase. The atomic valance index (V topo) of the C16 atom is low compared with other carbon atoms; this shows that C16 could be the possible reactive location of the AGH molecule. All atoms in the OH groups have very low V topo values; this indicates their role in strong hydrogen bonding interactions. The electrostatic potential (ESP) surface of AGH shows the polarization of the C16=C17 bond and ESP contour map shows several maxima at the vicinity of the C16 atom; these results strongly demonstrate that the C16 atom is the reactive location of the AGH molecule. The molecular covalent docking analysis of AGH with the NF-κB receptor has been performed and confirmed this result. The highly electronegative region around γ-butyrolactone can be helpful for initial alignment of the AGH molecule in NF-κB receptor active site. The atomic volumes of the hydrogen atoms which participate in the H...H interaction are found to be low.