Phytosterols and triterpenes from Morinda lucida Benth. exhibit binding tendency against class I HDAC and HDAC7 isoforms
- 75 Downloads
The important role of histone deacetylases (HDACs) in the development of cancer has been demonstrated by various studies. Thus targeting HDACs with inhibitors is a major focus in anticancer drug research. Although few synthetic HDAC inhibitors (HDIs) have been approved for cancer treatment, they have significant undesirable side effects. Therefore emphases have been placed on natural HDIs as substitutes for the synthetic ones. In a bid to identify more HDIs, this study evaluated the binding tendency of compounds derived from Morinda lucida Benth. towards selected HDACs for the discovery of potent HDIs as potential candidates for anticancer therapeutics, based on the report of anticancer potentials of Morinda lucida-derived extracts and compounds. Givinostat and 49 Morinda-lucida derived compounds were docked against selected HDAC isoforms using AutodockVina, while binding interactions were viewed with Discovery Studio Visualizer, BIOVIA, 2016. Druglikeness and Absorption–Distribution–Metabolism–Excretion (ADME) parameters of the top 7 compounds were evaluated using the Swiss online ADME web tool. The results revealed that out of the 49 compounds, 3 phytosterols (campesterol, cycloartenol, and stigmasterol) and 2 triterpenes (oleanolic acid and ursolic acid) exhibited high HDAC inhibitory activity compared to givinostat. These 5 compounds also fulfill oral drugability of Lipinski rule of five. Morinda lucida-derived phytosterols and triterpenes show high binding tendency towards the selected HDACs and exhibited good drugability characteristics and are therefore good candidates for further studies in the search for therapies against abnormalities linked with over-activity of HDACs.
KeywordsHDACs Morinda lucida Anticancer Phytosterols Triterpenes
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 1.Reddy DS, Wu X, Golub VM et al (2018) Measuring histone deacetylase inhibition in the brain. Curr Protoc Pharmacol 1–14. https://doi.org/10.1002/cpph.41
- 10.Ganai S (2016) Novel approaches towards designing of isoform-selective inhibitors against class ii histone deacetylases: the acute requirement for targetted anticancer therapy. CurrTopMedChem 16:2441–2452Google Scholar
- 21.Park S, Jun J, Jeong K (2011) Histone deacetylases 1, 6 and 8 are critical for invasion in breast cancer. Oncol Rep 25:677–1681Google Scholar
- 28.Ashidi JS, Houghton PJ, Hylands PJ, Efferth T (2010) Ethnobotanical survey and cytotoxicity testing of plants of South-western Nigeria used to treat cancer, with isolation of cytotoxic constituents from Cajanus cajan Millsp. leaves. J Ethnopharmacol 128:501–512. https://doi.org/10.1016/j.jep.2010.01.009 CrossRefGoogle Scholar
- 30.Appiah-opong R, Tuffour I, Annor GK et al (2016) Antiproliferative, antioxidant activities and apoptosis induction by Morinda lucida and Taraxacum officinale in human HL-60 leukemia cells. J Glob Biosci 5:4281–4291Google Scholar
- 33.Suzuki M, Tung HN, Kwofie KD et al (2015) New anti-trypanosomal active tetracyclic iridoid isolated from Morinda lucida Benth. Biorgan Med Chem Lett http://dx:1–4. https://doi.org/10.1016/j.bmcl.2015.05.003
- 35.Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31:455–461Google Scholar
- 42.Raj RA, John Milton MC, Prakasam A et al (2018) In silico molecular docking of bioactive compound Pregnan-20-one,5,6-epoxy-3,17,dihydroxy-16 methyl-[3a,5a,6a,16a] with brain cancer protein(1qh4): a promising molecular target. 9:51–55Google Scholar
- 47.Zhang Z, Luo Z, Shi H et al (2017) Research advance of functional plant pharmaceutical cycloartenol about pharmacological and physiological activity. J Chinese Mater medica 42:433–437Google Scholar
- 52.Chen I, Lu M, Du Y et al (2009) Cytotoxic triterpenoids from the stems of Microtropis japonica. J Nat Prod 72:6–11Google Scholar