Vol.:(0123456789) 1 3 Molecular Biology Reports https://doi.org/10.1007/s11033-019-04689-8 ORIGINAL ARTICLE Phytosterols and triterpenes from Morinda lucida Benth. exhibit binding tendency against class I HDAC and HDAC7 isoforms Ahmed Adebayo Ishola 1  · Kayode Ezekiel Adewole 2 Received: 11 December 2018 / Accepted: 7 February 2019 © Springer Nature B.V. 2019 Abstract 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 signifcant undesirable side efects. 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 evalu- ated 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 fulfll oral drugability of Lipinski rule of fve. Morinda lucida-derived phytosterols and triterpenes show high binding tendency towards the selected HDACs and exhibited good drugability char- acteristics and are therefore good candidates for further studies in the search for therapies against abnormalities linked with over-activity of HDACs. Keywords HDACs · Morinda lucida · Anticancer · Phytosterols · Triterpenes Introduction Histone deacetylases (HDACs) are target enzymes in the epigenetic modulation of genomic activity and may be exploited in the treatment of many diseases, including cancer [1]. Cancer is currently one of the serious health challenges facing the world, killing about 9 million people in 2015 [2]. It is the cause of 1 in every 6 deaths reported globally; out of which low and middle-income nations account for about 70% [2]. Cancer is caused by altered cell chemistry upsetting the delicate control of cell cycle, angiogenesis, apoptosis and other vital cellular processes [3, 4]. It has now been confrmed that apart from genetic changes, progression of cancer could also be caused by altered epigenetic processes without modifcation in DNA sequence [5]. These epige- netic processes include methylation of DNA, modifcation of histone protein and non-coding RNA deregulation [5]. The important role of epigenetic mechanisms in the development of cancer has been demonstrated by various studies, and his- tone acetylation is one of such key epigenetic processes [6]. Histone acetylation is maintained in active balance by his- tone acetyl transferases and histone deacetylases [7]. HDACs catalyze the removal of acetyl group from N-terminal lysine side chain of histone and non-histone proteins. This revers- ible process is one of the most common events in post-trans- lational modifcations. Aberrant protein acetylation has been linked to cancer while abnormal expression of HDACs has been established in various cancer types [8]. The role of HDACs in this important epigenetic process has therefore made them promising targets of anticancer drug discovery * Kayode Ezekiel Adewole kayowolemi@gmail.com 1 Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin, Nigeria 2 Biochemistry Unit, Department of Chemical Sciences, Faculty of Natural Sciences, Ajayi Crowther University Oyo, Oyo, Oyo State, Nigeria