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-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-HÁ Á ÁO and weak C-HÁ Á ÁO types of intermolecular interactions. The dissociation energy of the strong hydrogen bond O2-H22Á Á ÁO1 is very high, 32 kJ mol À1 . The percentage occupancy of HÁ Á ÁH 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-B receptor has been performed and confirmed this result. The highly electronegative region around -butyrolactone can be helpful for initial alignment of the AGH molecule in NF-B receptor active site. The atomic volumes of the hydrogen atoms which participate in the HÁ Á ÁH interaction are found to be low.

Diterpenes/Diterpenoids and Their Derivatives as Potential Bioactive Leads against Dengue Virus: A Computational and Network Pharmacology Study

“…The 2D and 3D structures of non-bond interactions of triptolide, stevioside, sphaeropsidin A, and caesalacetal with the target protein NS1 are shown in Figure 6. Andrographolide is a lactone diterpene, isolated from Andrographis paniculata, and possesses many biological effects, including antioxidant [39], anti-inflammatory [40], neuroprotective [41], hepatoprotective [42], anti-viral [43][44][45], anti-thrombotic [46], anticancer [47], and others. This diterpene lactone at 100 and 200 µM concentration showed an anti-DENV effect via GRP78 interaction pathway and at 5, 10, 15, and 25 ppm, a concentration larvicidal effect by inducing cytopathic effects in the midgut epithelium (LC 50 : 12 ppm) [23].…”

Andrographolide, A Natural Antioxidant: An Update

“…It is a lactone diterpene that gives the plant a bitter taste. Many studies have focused on the anti-viral [12][13][14], anti-thrombotic [15,16], hepatoprotective [17,18], anticancer [19,20], and anti-inflammatory properties [21] of andrographolide. Several data have reported the antioxidant activities of andrographolide in various in vitro and in vivo model systems [22,23].…”

Experimental and theoretical charge density, intermolecular interactions and electrostatic properties of metronidazole

“…Such properties of molecular crystals can be obtained from high-resolution X-ray diffraction data at low temperatures. From high-resolution X-ray diffraction data, we can obtain the one-electron properties associated with molecules in crystals from the Hansen and Coppens multipole formalism (Hansen & Coppens, 1978), the details of which have been discussed in depth in our recent works (Rajalakshmi et al, 2014a,b;Kalaiarasi et al, 2016;Manjula et al, 2018;Iruthayaraj et al, 2019). The nature of intermolecular interactions has been analysed from the electron-density distribution as these are the building blocks of the molecular crystal packing (Coppens, 1997;Koritsanszky & Coppens, 2001).…”