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Role of radical quenching activity of dihydrocanaric acid in the treatment of cancer-experimental and theoretical

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Abstract

In the present study, we have experimentally and theoretically studied the free-radical quenching property of dihydrocanaric acid (DCA) isolated from seedpods of Holarrhena antidysenterica. A modified method was used to estimate the nitric oxide scavenging effect of the DCA (significant activity of 75.22%) along with methanolic extract of seed pods of Holarrhena antidysenterica (72.80%) compared to the ascorbic acid as standard (40.60%). Studies have also been conducted for superoxide scavenging activity of the DCA (78.82%) and methanolic extract of seed pods (84.28%) compared to quercetin as standard (82.08%). Theoretically, it has been determined by density-functional theory(DFT) calculations using M06-2X hybrid functional and the double-ζ- split-valence 6-31G (d, p) basis set that the nitric oxide scavenging activity of the compound is by the addition of NO radical at double bond position. Predicted biological activity profile of DCA suggests that it has less activity probability (Pa) for toxicity (Pa = 0.730), cytotoxicity (Pa = 0.208), compared to those chemical entities that are already known as anticancer agents indicating that DCA is less toxic and more tolerable for normal cells. Furthermore, molecular docking studies of the DCA with different studied cancer-related receptors [Estrogen receptor (− 60.12 kcal/mol), epidermal growth factor receptor (EGFR) (− 30.33 kcal/mol), estrogen receptor alpha (− 4.82 kcal/mol), uPAR (− 32.55 kcal/mol) and an enzyme having lipid kinase activity phosphoinositide 3-kinase (− 55.94 kcal/mol)] were found to have better binding affinities compared to betulinic acid and doxorubicin. Thus, our findings suggest that the DCA could be a safer and effective alternative in fighting cancer with minimal side effects.

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Acknowledgements

Sincere thanks to the Department of Science and Technology-WOS (A) for financial assistance (Project No. SR/WOS(A)/CS-157/2016). Dr.Kuheli Chakrabarty, Department of Chemistry, Visva Bharati for her support. Professor Julie Banerji Ex-professor of Calcutta University, India, Professor Avijit Banerji, Department of Chemistry, National Research Institute for Ayurvedic Drug Development, Kolkata, India, and Dr.Manoj Kar, Nil Ratan Sircar Medical College and Hospital, Kolkata, India for their initial help. Sincere thanks to the Director, Chittaranjan National Cancer Institute, Kolkata, India.

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Authors and Affiliations

  1. Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P.Mukherjee Road, Kolkata, 700 026, India

    Anindita Ghosh & Chinmay Kumar Panda

  2. CSIR-National Botanical Research Institute, Rana Pratap Marg, PO Box No. 436, Lucknow, 226001, India

    Gopal Ji Tiwari

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  1. Anindita Ghosh
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  2. Gopal Ji Tiwari
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  3. Chinmay Kumar Panda
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AG: Experimental work and manuscript writing. GJT: Bioinformatics analysis and manuscript writing. CKP: Helped in analysis and manuscript writing.

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Correspondence to Anindita Ghosh.

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Ghosh, A., Tiwari, G.J. & Panda, C.K. Role of radical quenching activity of dihydrocanaric acid in the treatment of cancer-experimental and theoretical. 3 Biotech 10, 251 (2020). https://doi.org/10.1007/s13205-020-02221-5

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