Predicting potential antitumor targets of Aconitum alkaloids by molecular docking and protein–ligand interaction fingerprint
Aconitine compounds are found in Aconitum Ouwu head, Chuan Wu, Aconitum, and other Ranunculaceae aconitum plants, which are not only active ingredient but also toxic component. In present study, 20 antitumor target proteins of different types were selected from Protein Data Bank (http://www.rcsb.org), for the purpose of finding potential antitumor targets of aconitum alkaloids, top ranked proteins were screened by molecular docking method, using the docking module in Sybyl-X 1.1 and Molecular Operating Environment (MOE) 2008, and screening result was verified by protein–ligand interaction fingerprint (PLIF) in MOE. Mesaconitine showed a C-shaped conformation when docking into heat-shock protein 90 (HSP90), which was similar with ANSA ring of geldanamycin. And the PLIF indicated that they shared many common amino acid residues interacted with HSP90; equally, Yunaconitine was found having similar conformation with the inhibitor of poly ADP-ribose polymerase-1 (PARP-1).
KeywordsAconitum alkaloids Antitumor Potential target Protein–ligand interaction fingerprint (PLIF) Molecular docking Heat-shock protein 90 (HSP90) Poly ADP-ribosepolymerase-1 (PARP-1)
This work was supported by Chinese national science foundation with Grant Nos. 81274182, 81303315, 81573687.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interests.
- Gao LM, Mao XF, Wei XM, Zheng S (1999) Diterpenoid alkaloids of pharmacological effects and structure–activity relationship profiles. Chin J Northwest Norm Univ Nat Sci 39:98–102Google Scholar
- Hu H, Rao Z, Xu J, Zhu Q, Altenbach H-J, Chen H, Zhou D, Xiao Y, Ke X, Guo H (2012) 16-Morpholino quaternary ammonium steroidal derivatives as neuromuscular blocking agents: synthesis, biological evaluation and in silico probe of ligand-receptor interaction. Eur J Med Chem 56:332–347CrossRefPubMedGoogle Scholar
- Huang YR (1991) Aconitum cancer studies. Fujian Trad Chin Med 22:54–56Google Scholar
- Meng S, Shan GZ, Li ZR (2011) Recent progress in the study of Hsp90 inhibitors. Chin J Antibiot 36:241–248Google Scholar
- MOE Molecular Operating Environment (2008) version 2008. Chemical Computing Group Inc., Montreal, QC, CanadaGoogle Scholar
- SYBYL, Tripos Inc. http://www.tripos.com/
- Wang YX, Jia K, Zhang DS (1989) Aconitine on immune function in rats. Trad Chin Med Info 9:40–41Google Scholar