A Computational Approach to Drug Discovery: Search for Chalcone Analogues as the Potential Candidates for Anti Colorectal Cancer (HT29)
Keywords:2D QSAR, 3D QSAR, docking, molecular dynamic, pharmacophore, HT29
A series of 46 chalcone derivative compounds with their inhibitory activity against colorectal cancer were used as data set for developing the quantitative structure activity relationship (QSAR). 2D QSAR and 3D QSAR models have been developed with high predictive ability with r2 and r2(CV) of 0.81 and 0.78, respectively. Results from the 2D and 3D quantitative structure activity relationship models indicate that electrostatic parameter enhanced bioactivity of the chalcone derivatives. Further, docking and molecular dynamic simulation was performed using 2wft PDB ID as the molecular target of colon cancer. Based on the docking, molecular dynamic, and biological assay, it is confirmed that compound 2, cpd 4, cpd 21, cpd 23, cpd 27, cpd 32, cpd 38, and cpd 39 show better activity (active) against colorectal cancer cells.
HK Sieh, LT Tsao, JP Wang and CN Lin. Synthesis and anti-inflammatory effect of chalcones. J. Pharm. Pharmacol. 2000; 52, 163-71.
D Dragana, BM Marina, I Branka and C Ivana. Antibacterial activity of three newly-synthesized chalcones & synergism with antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus. Indian J. Med. Res. 2014; 140, 130-7.
G Deepa and DK Jain. Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity. J. Adv. Pharm. Tech. Res. 2015; 6, 114-7.
DK Mahapatra, SK Bharti and V Asati. Anti-cancer chalcones: Structural and molecular target perspectives. Eur. J. Med. Chem. 2015; 15, 69-114.
AM Zeinab, ME Mastoura, AM Rasha, FMG Sobhi, SA Seham and NM Yahia. Synthesis, antitumor evaluation and molecular docking of new morpholine based heterocycles. Molecules 2017; 22, 1211-25
C Yu-Chien. Beware of docking. Trend Pharm. Sci. 2014; 36, 617.
CW Mai, M Yaeghoobi, NA Rahman, YB Kang and MR Pichika. Chalcones with electron-withdrawing and electron-donating substituents: Anticancer activity against TRAIL resistant cancer cells, structure-activity relationship analysis and regulation of apoptotic proteins. Eur. J. Med. Chem. 2014; 77, 378-87.
J Jasril, I Ihsan, Z Adel, YT Hilwan and F Neni. New fluorinated chalcone and pyrazoline analogs: synthesis, docking and molecular dynamic studies as anticancer agents. Thai J. Pharmaceut. Sci. 2017; 41, 93-8.
R Amit, R Vinit, KS Ashok, KK Amit, K Umesh, K Dinesh and S Sudipta. Design and synthesis of 1,4-benzothiazine derivatives with promising effects against coloerectal cells. Cogent Chem. 2017; 3, 1-24.
Z Adel, F Neni and YT Hilwan. Docking and molecular dynamic simulations: Study of 1, 3, 4-oxadiazolechalcone hybrid derivatives to search new active anticancer agents. Thai J. Pharmaceut. Sci. 2016; 40, 179-84.
H Adam, RG Josep, O Modesto and LG Josep. Molecular dynamic simulations: Advances and application. Adv. Appl. Bioinform. Chem. 2015; 8, 37-47.
How to Cite
Copyright (c) 2018 Walailak Journal of Science and Technology (WJST)
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.