Exploring inhibitory potential of Curcumin against various cancer targets by in silico virtual screening.
Various types of cancer accounts for 10% of total death worldwide which necessitates better therapeutic strategies. Curcumin, a curcuminoid present in Curcuma longa, shown to exhibit antioxidant, anti-inflammatory and anticarcinogenic properties. Present study, we aimed to analyze inhibitory properties of curcumin towards virulent proteins for various cancers by computer aided virtual screening. Based on literature studies, twenty two receptors were selected which have critical virulent functions in various cancer. The binding efficiencies of curcumin towards selected targets were studied by molecular docking. Out of all, curcumin showed best results towards epidermal growth factor (EGF), virulent protein of gastric cancer; glutathione-S-transferase Pi gene (GST-PI), virulent protein for prostate cancer; platelet-derived growth factor alpha (PDGFA), virulent protein for mesothelioma and glioma compared with their natural ligands. The calculated binding energies of their docked conformations with curcumin found to be -7.59 kcal/mol, -7.98 kcal/mol and -7.93 kcal/mol respectively. Further, a comparative study was performed to screen binding efficiency of curcumin with two conventional antitumor agents, litreol and triterpene. Docking studies revealed that calculated binding energies of docked complex of litreol and EGF, GST-PI and PDGFA were found to be -5.08 kcal/mol, -3.69 kcal/mol and -1.86 kcal/mol respectively. The calculated binding energies of triterpene with EGF and PDGFA were found to be -4.02 kcal/mol and -3.11 kcal/mol respectively, whereas GST-PI showed +6.07 kcal/mol, indicate poor binding. The predicted pharmacological features of curcumin found to be better than litreol and triterpene. Our study concluded that curcumin has better interacting properties towards these cancer targets than their normal ligands and conventional antitumor agents. Our data pave insight for designing of curcumin as novel inhibitors against various types of cancer.
R & D Center, Department of Biotechnology, Dayananda Sagar College of Engineering, Bangalore, 560078, Karnataka, India.
Arpitha Badarinath
AB
Mahajanakatti
Geetha
G
Murthy
Narasimha
N
Sharma
Sinosh
S
Skariyachan
D000284:Administration, Oral; D000465:Algorithms; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D000975:Antioxidants / Q000737:chemistry; D018938:Caco-2 Cells; D002396:Catechols / Q000737:chemistry; D003474:Curcumin / Q000737:chemistry*; D004285:Dogs; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D004815:Epidermal Growth Factor / Q000378:metabolism; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D006801:Humans; D008024:Ligands; D061985:Madin Darby Canine Kidney Cells; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011485:Protein Binding; D014315:Triterpenes / Q000737:chemistry
D000970:Antineoplastic Agents; D000975:Antioxidants; D002396:Catechols; D008024:Ligands; D010982:Platelet-Derived Growth Factor; D014315:Triterpenes; C075278:platelet-derived growth factor A; D004815:Epidermal Growth Factor; C048342:3-(pentadec-10-enyl)catechol; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D003474:Curcumin