Nahid Askari
1 
, Morteza Hadizadeh
2 , Mohammad Sina
3 , Sepideh Parvizpour
4* , Seyedeh Zahra Mousavi
5* , Mohd Shahir Shamsir
61 Department of Biotechnology, Institute of Sciences and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran
2 Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
3 A. Nocivelli Institute for Molecular Medicine, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
4 Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
5 Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
6 Bioinformatics Research Group (BIRG), Department of Biosciences, Faculty of Science, Universiti Teknologi Malaysia, Skudai, Johor, Malaysia
Abstract
Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a poor prognosis. Kinase proteins are essential regulators of cellular processes and potential targets for drug development.
Methods: Integration of multiple microarray datasets was screened to find differentially expressed kinases (DE-Kinases) across adjacent normal and tumor tissue samples in PDAC. The most effective kinase for drug design and docking in this study was selected by investigating biological mechanisms and survival analyses. Forty phytochemicals were extracted from the yellow sweet clover, Melilotus officinalis (Linn.) Pall, and were then subjected to in silico screening and molecular docking studies against a specific potent kinase.
Results: MET, PAK3, and PDK4 were identified as the DE-Kinases. After examining the pathways and biological processes, up-regulated MET had the most significant survival analysis and became our primary kinase for drug design and docking in this study. Four of the extracted phytocompounds of Melilotus officinalis (Linn.) Pall that exhibited high binding affinities with MET and were selected for toxicity analysis. Finally, the stability and mobility of the two nontoxic compounds that passed the toxicity test (dicumarol PubChem CID: 54676038 and melilotigenin PubChem CID: 14059499) were studied by molecular dynamics simulation.
Conclusion: This study's results identified two phytochemicals in yellow sweet clover that could be used to develop an anticancer drug, but experimental evaluation is necessary to confirm their efficacy.