Screening of plant-derived natural compounds as potent chemotherapeutic agents against breast cancer: An in silico approach
Muhammad Kalim, Asad Ullah Khan, Mohammad Haris Siddiqui, Salman Akhtar, Khurshid Ahmad, Khwaja Osama · Journal of chemical and pharmaceutical research · 2015
In present study, we aimed to investigate the chemo therapeutic potential of 27 dietary phytochemicals with the motive of developing in silico protocol against tra nscription factor- NF-κB; growth factor-EGF; antiapoptotic proteins-Bcl-2 and survivin; protein kinase-HER-2; cell cycle protein-cyclin D1 and metastasis protein s-5-LOX, COX2 and VEGF. 2-D structures of all phytochemicals were retrieved from PubChem Compound database and their subsequent conversion into 3-D structures was performed by using online software system CORINA. The X-ray crystallographic structure of proposed target prote ins was extracted from RCSB Protein Data Bank. Mole cular docking simulation study was carried out by using A utoDock Tools 4.0. The docking results revealed that quercetin (BE: -7.75 Kcal/mol; Ki: 385.26 nM) exhibited bette r binding interaction to NF-κB than its known inhibitors. Resveratrol (-7.11 Kcal/mole; 6.12 µM) was found to bind to EGF with tighter interaction than several reported EGF inhibitors. Quercetin (-7.86 Kcal/mole; 1.72 µM ) and guggulsterone (-7.90 Kcal/mole; 1.62 µM) were best bound to Bcl-2 and Survivin respectively. Emodin (- 7.60 Kcal/mole; 2.69 µM) was best docked with HER-2 . Guggulsterone (-9.84 Kcal/mole; 60.76 nM) was furth er best bound to Cyclin D1. Moreover, dibenzoylmeth ane (8.05 Kcal/mole; 1.25 µM), guggulsterone (-11.15 Kca l/mole; 0.0067 µM) and Quercetin (-8.75 Kcal/mole; 0.3852 µM) showed very good binding interaction with 5-LOX , COX2 and NF-κB respectively. Our in silico findings have explored the chemopreventive potential of phytoche micals and further, being natural, they have minima l or null side effects on human body as compared to the synth esized anti-breast cancer agents and thus could be their promising alternatives.