Current Biotechnology Send Orders for Reprints to reprints@benthamscience.net Current Biotechnology, 2019, 8, 127-137 127 RESEARCH ARTICLE In Silico Target Identification and Molecular Docking Studies of Natural Cytotoxic Compound Borivilianoside H S. Dutta Gupta 1,* and P. Kohli 1 1 Department of Agricultural and Food Engineering, Indian Institute of Technology Kharagpur, Kharagpur 721302, India Abstract: Background: Borivilianoside H is a naturally occurring anti-cancer compound with known cytotoxicity against human colorectal cancer cell line (HCT-116) and human adenocarcinoma cell line (HT-29). The present study describes the pharmacophore modelling, molecular docking, and molecular dynamics simulation approaches to predict the target proteins of borivilianoside H along with its bind- ing affinity to the selected proteins. Methods: A 3-dimensional structure of borivilianoside H was constructed using Avogadro from its 2-D coordinates retrieved from the Pubchem Compound database. Target proteins associated with cancers were identified based on the 95% normalized fit score of PharmMapper. The crystal structures of the targets were retrieved from Protein Data Bank and molecular docking was performed with Autodock Vina 1.1.2. MD simulations were carried out via Google Cloud Platform. ADMET characteristics for borivilianoside H were determined using admetSAR web server. Results: Among the selected 7 top-ranked target proteins, fibroblast activation protein (FAP) exhibited the highest binding affinity followed by serum albumin (ALB), bone morphogenetic protein 2 (BMP2) and kinesin-like protein 11 (KIF11). However, the best fit was found with KIF11, where both the ste- roidal and oligosaccharide moieties of borivilianoside H were involved in interacting with the protein cavity. KIF11 was thus found to be the most suitable target for the anti-cancer effect of borivilianoside. ADMET analysis revealed its suitability as an intravenous drug. Conclusion: The targets predicted using this approach will serve as leads for the possible use of borivilianoside H, one of the active ingredients of Chlorophytum borivilianum as an anti-cancer drug. A R T I C L E H I S T O R Y Received: July 22, 2019 Revised: August 28, 2019 Accepted: October 21, 2019 DOI: 10.2174/2211550108666191112115330 Keywords: Borivilianoside H, anti-cancer drug, pharmacophore modelling, molecular dynamics, KIF-11, in silico. 1. INTRODUCTION Cancer cells are known to develop drug resistance very rapidly [1]. To avoid this phenomenon, the drugs are admin- istered in combination. The pharmaceutical market needs to be updated with new drugs every year to develop effective treatment courses against this deadly disease. A variety of natural products have been screened for various pharmaceu- tical applications and drug developments [2, 3]. About three- quarters of the clinically approved anti-cancer drugs are nat- ural, naturally-derived, natural mimic, or semi-synthetic products [3]. Natural products hold the highest probability of making it through clinical trials. Phytochemicals have a large pool of anti-cancer compounds. *Address correspondence to this author at the Department of Agricultural and Food Engineering, Indian Institute of Technology Kharagpur, Kharag- pur 721302, India; Tel/Fax: +91-3222-283114, +91-3222-282244; E-mail: sdg@agfe.iitkgp.ac.in Hence, the drug potential of traditional medicinal plant products needs to be explored. Chlorophytum borivilianum a medicinal herb belongs to the family Liliaceae is valued for its tuberous roots with aph- rodisiac potential [4]. Tuberous roots contain steroidal sapo- nins and are widely used in Ayurvedic medicine for the treatment of male impotence, and as diuretic, hemostatic and curative agents in various diseases [5]. The anti-tumour po- tential of this plant has also been demonstrated [6]. Among the 8 unique steroidal saponins identified, which are named as borivilianosides (A-H), only borivilianoside H is known to possess cytotoxic activity against HCT-116 (IC50 = 0.38 µM) and HT-29 (IC50 = 2.6 µM) colorectal cancer cell lines [7]. However, the therapeutic potential of this saponin as an ideal candidate for developing chemo-drug for various types of cancer has not yet been explored. One of the approaches to proceed further is to find its target protein that may have a role in oncogenesis. 2211-551X/19 $58.00+.00 © 2019 Bentham Science Publishers