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

Andrographolide (AGH) is a hepatitis C anti-viral agent which targets the host cell by covalently binding with the NF-kappa Breceptor. 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 center dot center dot center dot O and weak C-H center dot center dot center dot O types of intermolecular interactions. The dissociation energy of the strong hydrogen bond O2-H22 center dot center dot center dot O1 is very high, 32 kJ mol(-1). The percentage occupancy of H center dot center dot center dot 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-kappa B receptor has been performed and confirmed this result. The highly electronegative region around gamma-butyrolactone can be helpful for initial alignment of the AGH molecule in NF-kappa B receptor active site. The atomic volumes of the hydrogen atoms which participate in the H center dot center dot center dot H interaction are found to be low.