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. 2013 Sep 24;8(9):e74761.
doi: 10.1371/journal.pone.0074761. eCollection 2013.

In silico and in vivo anti-malarial studies of 18β glycyrrhetinic acid from Glycyrrhiza glabra

Komal Kalani  1 , Jyoti Agarwal, Sarfaraz Alam, Feroz Khan, Anirban Pal, Santosh Kumar Srivastava
Affiliations

In silico and in vivo anti-malarial studies of 18β glycyrrhetinic acid from Glycyrrhiza glabra

Komal Kalani et al. PLoS One. .

Abstract

Malaria is one of the most prevailing fatal diseases causing between 1.2 and 2.7 million deaths all over the world each year. Further, development of resistance against the frontline anti-malarial drugs has created an alarming situation, which requires intensive drug discovery to develop new, more effective, affordable and accessible anti-malarial agents possessing novel modes of action. Over the past few years triterpenoids from higher plants have shown a wide range of anti-malarial activities. As a part of our drug discovery program for anti-malarial agents from Indian medicinal plants, roots of Glycyrrhizaglabra were chemically investigated, which resulted in the isolation and characterization of 18β-glycyrrhetinic acid (GA) as a major constituent. The in vitro studies against P. falciparum showed significant (IC50 1.69 µg/ml) anti-malarial potential for GA. Similarly, the molecular docking studies showed adequate docking (LibDock) score of 71.18 for GA and 131.15 for standard anti-malarial drug chloroquine. Further, in silico pharmacokinetic and drug-likeness studies showed that GA possesses drug-like properties. Finally, in vivo evaluation showed a dose dependent anti-malarial activity ranging from 68-100% at doses of 62.5-250 mg/kg on day 8. To the best of our knowledge this is the first ever report on the anti-malarial potential of GA. Further work on optimization of the anti-malarial lead is under progress.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Schematic isolation, identification and bio-evaluation of anti-malarial lead, 18β-glycyrrhetinic acid (GA).
Figure 2
Figure 2. Schematic isolation of GA from G . glabra roots.
Figure 3
Figure 3. Chemical structures of glycyrrhizic acid (GL) and 18β-glycyrrhetinic acid (GA).
Figure 4
Figure 4. Structural model Plasmodium falciparum lactate dehydrogenase (pfLDH) (PDB: 1CEQ) with NADH binding site (yellow color)
(A). Superimposition of the best conformation of GA (in purple), CQ (in yellow) and NADH (in orange) in the active site pocket of P. falciparum enzyme lactate dehydrogenase pfLDH) (B). 2-D diagrams illustrating protein-ligand interactions: (C) Compound CQ; (D) Compound GA.
Figure 5
Figure 5. Adsorption model of the candidate compounds.
Figure 6
Figure 6. Drug likeness score of 0.9 for GA and 1.17 for CQ lie under the drugs range.
See this image and copyright information in PMC

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