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Structural Interactions of Curcumin Biotransformed Molecules with the N-Terminal Residues of Cytotoxic-Associated Gene A Protein Provide Insights into Suppression of Oncogenic Activities

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Abstract

Curcumin as a natural product has drawn considerable attention in recent years for its multiple pharmacological activities against various diseases, but more studies are required to understand the curcumin pharmacological action considering its low bioavailability. Though numerous reasons contribute to the low bioavailability of curcumin, one of the important reasons is associated with biotransformation of curcumin through either conjugation or reduction depending on curcumin administration route. The orally administered curcumin (CUR) is metabolised into curcumin glucuronidase (CUR-GLR) and curcumin sulphate by conjugation, whereas dihydroxycurcumin, tetrahydrocurcumin, and hexahydrocurcumin (HHC) are formed by reduction after intraperitoneal administration of curcumin. The main aim of the current study was to investigate the pharmacological properties of curcumin and its biotransformed molecules and its inhibitory potential against CagA (cytotoxic-associated gene A) oncoprotein of Helicobacter pylori. All lead molecules followed the Lipinski’s five rules for biological activities, except CUR-GLR, whereas druglikeness scores were obtained for all molecules. Subsequently, molecular docking was employed to analyse the binding affinity of molecules with CagA. The docking studies revealed that CUR-GLR has highest binding affinity with CagA, whereas less interactive affinity was observed in HHC. From the virtual screening and docking studies, the current study suggests that the biotransformation of curcumin through conjugation has more potential for inhibition of oncogenic activities of CagA+ H. pylori than reduction.

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Acknowledgments

We are thankful to the University Grant Commission project for Junior and Senior Research Fellowship (A/C-S01). We also thank School of Biotechnology, Banaras Hindu University, India, for guidance in bioinformatics studies.

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  1. Department of Botany, Banaras Hindu University, Varanasi, 221005, India

    Akhileshwar Kumar Srivastava, Divya Singh & Bijoy Krishna Roy

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Srivastava, A.K., Singh, D. & Roy, B.K. Structural Interactions of Curcumin Biotransformed Molecules with the N-Terminal Residues of Cytotoxic-Associated Gene A Protein Provide Insights into Suppression of Oncogenic Activities. Interdiscip Sci Comput Life Sci 9, 116–129 (2017). https://doi.org/10.1007/s12539-016-0142-2

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