Inhibition mechanism of cathepsin B by curcumin molecule: a DFT study


Cathepsin B is one of the attractive targets for cancer treatments due to its prominent role in tumor cell invasion and metastasis. Because of the increasing toxicity of available cancer drugs, it is essential to develop new drugs with less or no side effects. One of the natural compounds named curcumin has a well-documented history of medicine in India, which is currently in clinical trials for the treatment of various cancers. However, the inhibition mechanism of the curcumin molecule is not yet clear. In this present study, the inhibition of cathepsin B by the curcumin has been studied by quantum chemical methods using DFT method at M062X/6-31 + g(d,p)//B3LYP/6-31g(d) level of theory to obtain a complete picture of possible reaction paths. Based on the obtained results, the Cys29 can undergo nucleophilic attack at any one of the four reactive sites of the curcumin. The low activation energy 1.43 kcal/mol along with low negative reaction energy − 6.82 kcal/mol suggests that attack of Cys29 at C63 atom is the most feasible reaction path. These results suggest that curcumin can be used to develop less toxic cathepsin B inhibitors for the treatment of cancer disease.

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Transition state




Quantum theory of atoms in molecules


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The authors (C. Pitchumani Violet Mary and S.Vijayakumar) thank the Department of Science and Technology-Science and Engineering Research Board (DST-SERB), India, for awarding this research project under the OYS Scheme (Grant No. SR/FTP/PS-115/2011 dated September 19, 2013).

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Correspondence to S. Vijayakumar.

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Pitchumani Violet Mary, C., Vijayakumar, S. & Shankar, R. Inhibition mechanism of cathepsin B by curcumin molecule: a DFT study. Theor Chem Acc 138, 21 (2019).

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  • Cancer
  • DFT
  • Enzyme inhibition
  • Phytochemical compound
  • Quantum chemical calculation