THREE-DIMENSIONAL QUANTITATIVE STRUCTUREâ€“ACTIVITY RELATIONSHIPS MODELING STUDIES OF PHYTOCHEMICALS FROM BRASSICACEAE AS POTENT INHIBITORS AGAINST TUMOR INFLAMMATION
Objective: The aim of this study was to develop a three-dimensional quantitative structureâ€“activity relationships (3D-QSARs) model for studying theinteraction of different phytochemicals with nuclear factor kappa B (NF-Ä¸B) inducing kinase, a major regulator in tumor inflammation.
Methods: Different phytochemicals (ligands) from Brassicaceae were selected and tested for Lipinski's rule of five and further analyzed using interaction studies (docking) to identify the binding site in the target protein. Ligands with best fit were made to pass through ADMET filter, and the nontoxic ligands were selected based on the pIC50 values.
Results: The 3D-QSARs of the ligands were designed using comparative molecular field analysis, and glucoraphanin was found to be stable and fit after subjecting for molecular dynamics simulation with annealing studies.
Conclusion: Thus, the model may be prospectively used in drug design to find possible inhibitors of NF-Ä¸B, which plays a key prominent role in cancer inflammation.
Keywords: Three-dimensional quantitative structureâ€“activity relationships, Brassica oleracea, Simulation, Annealing, Nuclear factor kappa B kinase.
EirÃ³ N, Vizoso FJ. Inflammation and cancer. World J Gastrointest Surg 2012;4(3):62-72. development. Mol Cancer Res 2006;4(4):221-33.
Kadioglu O, Seo EJ. Targeting angiogenesis by phytochemicals. Med Aromat Plants 2013;2(5):1-8.
Russo M, Spagnuolo C, Tedesco I, Russo GL. Phytochemicals in cancer prevention and therapy: Truth or dare? Toxins (Basel) 2010;2(4):517-51.
Wagner AE, Tershulescen M. Health promoting effects of brassica- derived phytochemical: From chemopreventive and anti-inflammatory activities to epigenetic regulation. Oxid Med Cell Longev 2013;2013:Article ID: 964539, 12.
BjÃ¶rkman M, Klingen I, Birch AN, Bones AM, Bruce TJ, Johansen TJ, et al. Phytochemicals of Brassicaceae in plant protection and human health â€“ influences of climate, environment and agronomic practice. Phytochemistry 2011;72(7):538-56.
Talalay P, Fahey JW. Phytochemicals from cruciferous plants protect against cancer by modulating carcinogen metabolism. J Nutr 2001;131 11 Suppl:3027S-33.
Beecher CW. Cancer preventive properties of varieties ofBrassica oleracea: A review. Am J Clin Nutr 1994;59(5):1166-70.
Cartea ME, Francisco M, Soengas P, Velasco P. Phenolic compounds in Brassica vegetables. Molecules 2010;16(1):251-80.
Kumar S, Andy A. Health promoting bioactive phytochemicals from Brassica. Int Food Res J 2012;19(1):141-52.
Gadhe CG, Madhavan T, Kothandan G, Cho SJ. In silico quantitative structure-activity relationship studies on P-gp modulators of tetrahydroisoquinoline-ethyl-phenylamine series. BMC Struct Biol 2011;11:5.
Yadav DK, MeenaA, SrivastavaA, Chanda D, Khan F, Chattopadhyay SK. Development of QSAR model for immunomodulatory activity of natural coumarinolignoids. Drug Des Devel Ther 2010;4:173-86.
Priyadharshini SE, Ramalingam C, Ramesh B. Designing a novel Î² lactamase inhibitor by using docking and QSAR studies. Int J Pharm Pharm Sci 2014;6(4):516-23.
Zhang B, Li Y, Zhang H, Ai C. 3D QSAR and molecular docking studies on derivatives of MK-0457, GSK 1070916 and SNS 314 as inhibitors against aurora B kinase. Int J Mol Sci 2010;11:4326-47.
Sharma RB, Gogoi M, Baishya B, Johari S. 3D QSAR and docking studies of a series of Hamamelitannan derivatives as potential PBP4 inhibitors. Int J Pharm Pharm Sci 2014;6(6):558-62.
Devi JR, Thangam EB. Mechanism of anticancer activity of sulforaphane from Brassica oleracea in HEp-2 human epithelial carcinoma cell line. Asian Pac J Cancer Prev 2012;13(5):2095-100.
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