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. 2020 Feb 13;25(4):821.
doi: 10.3390/molecules25040821.

Anti-Neuraminidase Bioactives from Manggis Hutan (Garcinia celebica L.) Leaves: Partial Purification and Molecular Characterization

Muchtaridi Muchtaridi  1 , Milyadi Sugijanto  1 , Amirah Mohd Gazzali  2 , Habibah A Wahab  2   3
Affiliations

Anti-Neuraminidase Bioactives from Manggis Hutan (Garcinia celebica L.) Leaves: Partial Purification and Molecular Characterization

Muchtaridi Muchtaridi et al. Molecules. .

Abstract

The neuraminidase enzyme (NA) from the influenza virus is responsible for the proliferation and infections of the virus progeny, prompting several efforts to discover and optimize effective neuraminidase inhibitors. The main aim of this study is to discover a new potential neuraminidase inhibitor that comes from Garcinia celebica leaves (GCL). The bioassay-guided isolation method was performed to obtain lead compounds. The binding interaction of the isolated compounds was predicted by using molecular docking studies. Friedeline (GC1, logP > 5.0), two lanastone derivatives (methyl-3α,23-dihydroxy-17,14-friedolanstan-8,14,24-trien-26-oat (GC2) and 24E-3a,9,23-trihydroxy-17,14-friedolanostan-14,24-dien-26-oate (GC3) with LogP > 5.0) and catechin (GC4, LogP = 1.4) were identified. The inhibitory potency of these four compounds on NA from C. perfringens and H1N1 was found to be as follows: GC4 > GC2 > GC3 > GC1. All compounds exhibited higher inhibitory activity towards C. perfringens NA compared to H1N1 NA. From the molecular docking results, GC4 favorably docked and interacted with Arg118, Arg371, Arg292, Glu276 and Trp178 residues, whilst GC2 interacted with Arg118, Arg371, Arg292, Ile222, Arg224 and Ser246. GC3 interacted with Tyr406 only. GC4 had potent NA inhibition with free energy of binding of -12 kcal/mol. In the enzyme inhibition study, GC4 showed the highest activity with an IC50 of 60.3 µM and 91.0 µM for C. perfringens NA and H1N1 NA-respectively.

Keywords: Garcinia celebica; catechin; friedeline; lanastone; molecular docking.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Neuraminidase enzyme (NA) inhibition activity of Garcinia celebica leaves (GCL) extracts against (a) C. perfringens-NA and (b) H1N1-NA.
Figure 2
Figure 2
NA inhibition activity of n-hexane fractions of GCL against (a) C. perfringens–NA and (b) H1N1-NA.
Figure 3
Figure 3
Inhibition activity of isolated compounds from n-hexane fraction of GCL against (a) C. perfringens–NA and (b) H1N1-NA.
Figure 4
Figure 4
Neuraminidase inhibition activity of EtOAc fractions of GCL against (a) C. perfringens–NA and (b) H1N1-NA.
Figure 5
Figure 5
NA inhibition of isolated compound catechin as compared to DANA, as a gold standard against C. Perfringens-NA (blue) and H1N1-NA (purple).
Figure 6
Figure 6
Binding interaction of isolated compounds (a) GC2 and (b) GC3 from GCL against H1N1–NA (PDB code: 3B7E). (blue carbon: hydrophobic residues).
Figure 7
Figure 7
Binding interaction of GC4 from GCL against H1N1-NA (PDB code: 3B7E). (Blue carbon: hydrophobic residues).
See this image and copyright information in PMC

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