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. 2021 Jan 15;11(1):1594.
doi: 10.1038/s41598-021-81026-9.

Comprehensive computational _target fishing approach to identify Xanthorrhizol putative _targets

Muhammad Shahid  1 , Ahmad Azfaralariff  1 , Douglas Law  1 , Ahmed Abdulkareem Najm  1 , Siti Aisyah Sanusi  1 , Seng Joe Lim  1   2 , Yew Hoong Cheah  3 , Shazrul Fazry  4   5   6
Affiliations

Comprehensive computational _target fishing approach to identify Xanthorrhizol putative _targets

Muhammad Shahid et al. Sci Rep. .

Abstract

Xanthorrhizol (XNT), is a bioactive compound found in Curcuma xanthorrhiza Roxb. This study aimed to determine the potential _targets of the XNT via computational _target fishing method. This compound obeyed Lipinski's and Veber's rules where it has a molecular weight (MW) of 218.37 gmol-1, TPSA of 20.23, rotatable bonds (RBN) of 4, hydrogen acceptor and donor ability is 1 respectively. Besides, it also has half-life (HL) values 3.5 h, drug-likeness (DL) value of 0.07, oral bioavailability (OB) of 32.10, and blood-brain barrier permeability (BBB) value of 1.64 indicating its potential as therapeutic drug. Further, 20 potential _targets were screened out through PharmMapper and DRAR-CPI servers. Co-expression results derived from GeneMANIA revealed that these _targets made connection with a total of 40 genes and have 744 different links. Four genes which were RXRA, RBP4, HSD11B1 and AKR1C1 showed remarkable co-expression and predominantly involved in steroid metabolic process. Furthermore, among these 20 genes, 13 highly expressed genes associated with xenobiotics by cytochrome P450, chemical carcinogenesis and steroid metabolic pathways were identified through gene ontology (GO) and KEGG pathway analysis. In conclusion, XNT is _targeting multiple proteins and pathways which may be exploited to shape a network that exerts systematic pharmacological effects.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Structure of Xanthorrhizol (XNT).
Figure 2
Figure 2
(a) Network of co-expression of 20 common _targets of XNT constructed with GeneMANIA. The gene are linked to each other by the functional associated networks. Black nodes: gene _targets, color nodes represent top expressed genes and their molecular functions filtered on their FDR score, colored lines: represent different interactions. (b) The 8 highly co-expressed _targets from the GeneMANIA network identified via cytoscape.
Figure 3
Figure 3
(a) Bar plot of KEGG analysis showed top ten enriched pathways. (b) Drug-_target-pathway network constructed by cytoscape illustrated top ten pathways and their associated genes.
Figure 4
Figure 4
(a) Bar graph of top ten enriched biological processes (b) Drug-_target-biological process network constructed by cytoscape highlighted top ten BP and their linked genes.
Figure 5
Figure 5
Networks of top ten enriched molecular functions (a) and cellular components (b) constructed by Network Analyst. In both networks, nodes are color shaded according to their enrichment score (red > orange > yellow).
Figure 6
Figure 6
(a) PPI network constructed with STRING (The bold line represents direct interaction while the thin line represents indirect interaction), (b) Network of hub genes, and (c) two modules predicted by cytoHubba and MCODE plugins of cytoscape.
Figure 7
Figure 7
Docking results of XNT with (a) Cyclin-dependent kinase 2 (P24941), and (b) Progesterone receptor (P06401) selected proteins. Also showed their interacted amino acid residue types and numbers.
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