Computational simulation of inhibitory effects of curcumin, retinoic acid and their conjugates on GSK-3 beta
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Turmeric, since in ancient Indian traditional medicinal system, has been implicated for its therapeutic and chemopreventive properties against a broad spectrum of diseases. Curcumin, the active polyphenol from turmeric, helps to obstruct the growth of many types of cancers at various stages which include prostrate, melanoma, breast, brain tumor, pancreatic, leukemia, etc. The initiation and recurrence of cancer have been attributed to few mutated cells in bulk of tumor called as cancer stem cells which have the capacity of self-renewal and differentiation. Glycogen synthase kinase-3 beta (GSK-3B) is a multifunctional serine/threonine protein kinase, originally found in mammals, an important component of diverse signaling pathways, dysregulation of which leads to affect the cancer stem cell properties. The nutritional- and phytochemical-based dietary interventions may complement current chemotherapy to prevent recurrence and relapse of cancer. The objective of present study is to investigate the effect of retinoic acid and curcumin–retinoic acid conjugates against GSK-3B protein. The in silico results indicate that molecule 3 (curcumin–retinoic acid conjugates) might be a potent inhibitor of GSK-3B and a novel future drug candidate for the treatment of cancer.
KeywordsGSK-3B Curcumin Docking Cancer Computational Polyphenols
One of the authors, Rajesh K. Kesharwani, is thankful to Prof. Krishna Misra, Honorary Professor, Indian Institute of Information Technology, Allahabad, for her kind suggestion for completion of the work.
Compliance with ethical standards
Conflict of interest
The authors report no conflict of interest.
- Bharti AC, Donato N, Singh S, Aggarwal BB (2003) Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and Ikappa B alpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood 101(3):1053–1062CrossRefGoogle Scholar
- CLC drug discovery work bench/Molegro Virtual Docker: CLC Inc A, Denmark. http://www.clcbio.com/products/clc-drug-discovery-workbench. Accessed 25 Jan 2016
- Keservani RK, Kesharwani RK, Vyas N, Chadokar A (2010a) Nutritional supplements: an overview. Int J Curr Pharm Res 1(1):59–75Google Scholar
- Keservani RK, Kesharwani RK, Vyas N, Jain S, Raghuvanshi R, Sharma AK (2010b) Nutraceutical and functional food as future food: a review. Der Pharm Lett 2(1):106–116Google Scholar
- Kesharwani RK, Misra K (2011) Prediction of binding site for curcuminoids at human topoisomerase II α protein; an in silico approach. Curr Sci 101(8):1060–1064Google Scholar
- Kesharwani RK, Srivastava V, Singh P, Rizvi SI, Adeppa K, Misra K (2015) A novel approach for overcoming drug resistance in breast cancer chemotherapy by targeting new synthetic curcumin analogues against aldehyde dehydrogenase 1 (ALDH1A1) and glycogen synthase kinase-3 β (GSK-3β). Appl Biochem Biotechnol. https://doi.org/10.1007/s12010-015-1696-x CrossRefGoogle Scholar
- Upadhyaya J, Kesharwani RK, Misra K (2009) Metabolism, pharmacokinetics and bioavailability of ascorbic acid; synergistic effect with tocopherols and curcumin. J Comput Intell Bioinform 2(1):77–84Google Scholar