Acetogenins as potential checkpoint-2 kinase inhibitors: an in silico analysis
- 4 Downloads
Acetogenins are known anticancer agents present in the family Annonaceae. Drugs which can downregulate checkpoint kinase 2 (CHK2) in the ataxia telangiectasia mutated (ATM) signaling pathway are known to enhance chemosensitizing and radiosensitizing effects in cancer therapy. In the present study, the effect of 20 acetogenin compounds on CHK2 kinase is evaluated using Molecular docking studies. Twenty different acetogenin structures were retrieved from Pubchem. The physicochemical properties and absorption, distribution, metabolism, excretion, and toxicity (ADMET) were predicted. In silico virtual screening simulation was performed against CHK2 kinase. Among the 20 acetogenin compounds, Glabracin A showed the highest binding energy of − 14.9 kcal/mol. All the other acetogenins showed good binding energy of − 6.4 to − 7.4 kcal/mol with at least one or more hydrogen bonds. In silico analysis evidences acetogenins as good CHK2 inhibitors.
KeywordsAcetogenins CHK2 kinase Molecular docking ATM signaling pathway
All the authors thank Department of Biotechnology, Kuvempu University for providing the facilities to carry out the research work. The first author acknowledges the Department of Science and Technology, Women Scientist Scheme-A Grant No. SR/WOS-A/LS/461/2016(G) for financial support.
- DeLano WL (2002) ThePyMOL molecular graphics system. DeLano Scientific, San Carlos, CA, USA. http://www.pymol.org. Accessed 10 Oct 2014
- Jobson AG, Cardellina JH, Scudiero D, Kondapaka S, Zhang H, Kim H et al (2007) Identification of a Bis-guanylhydrazone [4, 4′-Diacetyldiphenylurea-bis (guanylhydrazone); NSC 109555] as a novel chemotype for inhibition of Chk2 kinase. Mol Pharmacol 72(4):876–884PubMedCrossRefPubMedCentralGoogle Scholar
- Moghadamtousi SZ, Rouhollahi E, Karimian H, Fadaeinasab M, Firoozinia M, Abdulla MA et al (2015) The chemopotential effect of Annona muricata leaves against azoxymethane-induced colonic aberrant crypt foci in rats and the apoptotic effect of acetogenin annomuricin E in HT-29 cells: a bioassay-guided approach. PloS One 10(4):e0122288CrossRefGoogle Scholar
- Pettit GR, Riesen R, Leet JE, Polonsky J, Smith CR, Schmidt JM, Dufresne C, Schaufelberger D, Moretti C (1989) Isolation and structure of rolliniastatin 2: a new cell growth inhibitory acetogenin from rollznza mucosa1. Heterocycles 28(7)Google Scholar
- Qayed WS, Aboraia AS, Abdel-Rahman HM, Youssef AF (2015) Annonaceous acetogenins as a new anticancer agent. Der Pharma Chemica 7(6):24–35Google Scholar
- Schüttelkopf AW, Van Aalten DMF (2004) PRODRG—a tool for high-throughput crystallography of protein-ligand complexes. Acta Crystallogr D60:1355–1363Google Scholar
- Torres MP, Rachagani S, Purohit V, Pandey P, Joshi S, Moore ED et al (2012) Graviola: a novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism. Cancer Lett 323(1):29–40PubMedPubMedCentralCrossRefGoogle Scholar
- Ye Q, He K, Oberlies NH, Zeng L, Shi G, Evert D, McLaughlin JL (1996) Longimicins A−D: Novel bioactive acetogenins from Asimina longifolia (Annonaceae) and structure−activity relationships of asimicin type of Annonaceous acetogenins. J Med Chem 39(9):1790–1796PubMedCrossRefPubMedCentralGoogle Scholar
- Zhou J, Xie G, Yan X (2011) Encyclopedia of traditional Chinese medicines. Isolat Compound AB 1:455Google Scholar