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. 2023 Jun;34(2):1-20.
doi: 10.21315/tlsr2023.34.2.1. Epub 2023 Jul 21.

In Silico Screening and Molecular Dynamics Simulation of Potential Anti-Malarial Agents from Zingiberaceae as Potential Plasmodium falciparum Lactate Dehydrogenase (PfLDH) Enzyme Inhibitors

Muhammad Fikri Heikal  1 , Wira Eka Putra  2 , Sustiprijatno  3 , Muhaimin Rifa'i  4 , Arief Hidayatullah  5 , Febby Nurdiya Ningsih  6 , Diana Widiastuti  7 , Adawiyah Suriza Shuib  8 , Baiq Feby Zulfiani  2 , Afrabias Firyal Hanasepti  2
Affiliations

In Silico Screening and Molecular Dynamics Simulation of Potential Anti-Malarial Agents from Zingiberaceae as Potential Plasmodium falciparum Lactate Dehydrogenase (PfLDH) Enzyme Inhibitors

Muhammad Fikri Heikal et al. Trop Life Sci Res. 2023 Jun.

Abstract

Malaria continues to be a major public health issue in a number of countries, particularly in tropical regions-the emergence of drug-resistant Plasmodium falciparum encourages new drug discovery research. The key to Plasmodium falciparum survival is energy production up to 100 times greater than other parasites, primarily via the PfLDH. This study targets PfLDH with natural bioactive compounds from the Zingiberaceae family through molecular docking and molecular dynamic studies. Sulcanal, quercetin, shogosulfonic acid C, galanal A and naringenin are the Top 5 compounds with a lower binding energy value than chloroquine, which was used as a control in this study. By binding to NADH and substrate binding site residues, the majority of them are expected to inhibit pyruvate conversion to lactate and NAD+ regeneration. When compared to sulcanal and control drugs, the molecular dynamics (MD) simulation study indicated that quercetin may be the most stable molecule when interacting with PfLDH.

Keywords: Anti-Malaria Drug; In Silico; Malaria; PfLDH; Zingiberaceae.

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Figures

Figure 1
Figure 1
3D visualisation of Top 5 natural compounds and control with PfLDH. (A) sulcanal, (B) quercetin, (C) shogasolfunic C, (D) galanal A, (E) naringenin, and (F) chloroquine (control). Red (Cofactor binding site domain), Purple (Substrate binding site domain), Yellow (Both substrate and cofactor binding site domain).
Figure 2
Figure 2
2D visualisation Top 5 compounds and control with PfLDH. (A) sulcanal, (B) quercetin, (C) shogasolfunic C, (D) galanal A, (E) naringenin, and (F) chloroquine (control).
Figure 3
Figure 3
3D visualisation of the ligand-PfLDH complex with binding site explanation. Red (Cofactor binding site domain), Purple (Substrate binding site domain), Yellow (Both substrate and cofactor binding site domain).
Figure 4
Figure 4
The potential binding energy of sulcanal (red), quercetin (green), and chloroquine (black) during MD simulation over 1,000 picosecond simulations.
Figure 5
Figure 5
(A) Root mean square deviation graph, (B) Root mean structure fluctuation graph, (C) Solvent accessible surface graphs, and (D) Radius gyration graphs for sulcanal (red), quercetin (green), and chloroquine (black) complex to PfLDH over a 1,000 picosecond of simulation.
See this image and copyright information in PMC

References

    1. Al-Adhroey AH, Nor ZM, Al-Mekhlafi HM, Mahmud R. Median lethal dose, antimalarial activity, phytochemical screening and radical scavenging of methanolic Languas galanga rhizome extract. Molecules. 2010;15(11):8366–8376. doi: 10.3390/molecules15118366. - DOI - PMC - PubMed
    1. Alam A, Neyaz MK, Hasan SI. Exploiting unique structural and functional properties of malarial glycolytic enzymes for antimalarial drug development. Malaria Research and Treatment. 2014 December;2014 doi: 10.1155/2014/451065. Article ID 451065. - DOI - PMC - PubMed
    1. Amadi SW, Zhang Y, Wu G. Research progress in phytochemistry and biology of Aframomum species. Pharmaceutical Biology. 2016;54(11):2761–2770. doi: 10.3109/13880209.2016.1173068. - DOI - PubMed
    1. Atkins P, Paula J. Physical chemistry. 9th Ed. New York: W. H. Freeman Co; 2010.
    1. Ayimele GA, Tane P, Connolly JD. Aulacocarpin A and B, nerolidol and β-sitosterol glucoside from Aframomum escapum. Biochemical Systematics and Ecology. 2004;32(12):1205–1207. doi: 10.1016/j.bse.2004.03.012. - DOI