Title: Molecular docking and in vitro study of Syzygium cumini-derived natural compounds on receptor tyrosine kinases pathway components

Authors: Pushpendra Singh; Felix Bast; Satej Bhushan; Richa Mehra; Pooja Kamboj

Addresses: Centre for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab 151001, India ' Centre for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab 151001, India ' Centre for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab 151001, India ' Centre for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab 151001, India ' Centre for Biosciences, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, Punjab 151001, India

Abstract: Syzygium cumini (S. cumini) is used for a variety of biological activities such as anti-inflammatory, anti-diabetic and anti-oxidant; currently, it has been reported for DNA protecting activity against radiation damage. Receptor tyrosine kinases (RTKs) are identified as critical regulators of various cellular processes including cell proliferation, metabolism and apoptosis. These receptors have recently gained attention as an attractive target for cancer treatment. The present research was aimed to screen S. cumini-derived natural compounds against RTKs pathway components using molecular docking. Furthermore, in vitro anti-proliferative 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and anti-oxidative (nitro blue tetrazolium and H2CDFD) activities of leaf extract of S. cumini are also reported. Selected natural compounds were docked with X-ray crystal structure of RTKs signalling proteins using grid-based ligand docking with energetics Maestro 9.6. In the present investigation, our result highlighted that myricetin, kaempferol, delphinidin chloride, ellagic acid, rutin, petunidin, gossypol and mirtillin generated a good dock score with all selected proteins. Protein-ligand interactions accentuated that several bonds such as lipophilic, hydrogen bonding, π-π stacking and cation-π interactions represent a ruling contribution at the active site. Moreover, reduction in cell viability with leaf extract of S. cumini treatment at concentrations of 5-80 µg/ml after 48 h in MCF-7 cells was observed. Leaf extract of S. cumini significantly reduced the Reactive oxygen species (ROS) generation in MCF-7 cells after 48 h. These results indicate the anti-cancer potential of S. cumini. Thus, isolation and purification of anti-cancerous compounds are suggested to explore more possibilities in the field.

Keywords: cancer; Maestro 9.6; natural product compounds; phosphoinositide-3 kinase; receptor tyrosine kinases.

DOI: 10.1504/IJBRA.2019.099576

International Journal of Bioinformatics Research and Applications, 2019 Vol.15 No.2, pp.144 - 158

Available online: 06 May 2019 *

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