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Anticancer potential of labdane diterpenoid lactone “andrographolide” and its derivatives: a semi-synthetic approach

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Abstract

Natural products have been a great source of pharmaceuticals since ages. Vast screening of natural products from different sources has led to the discovery of plethora of chemotherapeutic drugs and other compounds for the betterment of human life. Several bioactive entities have been generated by the structural modifications of the natural products or by using the natives as key models in synthetic chemistry. Nonetheless, a number of natural compounds with potential bioactivities remain unexploited in the medicinal field due to their stringent chemical properties. Andrographis paniculata Nees., a traditional medicinal herb from family Acanthaceae is known for its multiple pharmacological activities. It’s major bioactive constituent “andrographolide”, possesses promising anticancer potential and is one such unexploited treasure. The architecture of the molecule consists of an α-alkylidene γ-butyrolactone moiety, two olefin bond [Δ8(17) and Δ12(13)], three hydroxyls at C-3, C-19, and C-14 and highly substituted trans decalin. Of the three hydroxyl groups, one is allylic at C-14, and the others are secondary and primary at C-3 and C-19, respectively. By modification of the above structural features a number of andrographolide derivatives have been synthesized. The intricacy of the molecule has always been a constraint in developing a commercialized drug, nevertheless the efforts in this direction via synthetic chemistry are still continuous and prominent. The present review highlights the chemistry and anticancer activity of andrographolide. It discusses the limitations of the molecule as a pharmacological agent. Modifications in the key molecule along different moieties has been discussed which might lead to desirable bioactive molecules. The compiled information will be helpful in further developing specific modifications in andrographolide moiety which will have significant contribution in semi synthesis of anti-cancer agents.

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Acknowledgments

The authors would like to acknowledge Director, School of Biotechnology and Co-ordinator, Bioinformatics Centre, School of Biotechnology, University of Jammu for facilities. VS would like to thank Department of Science and Technology, Government of India for funding under WOS-A Project [SR/WOS-A/CS-111/2013 (G)]. Dr. Parthasarthi Das and Dr. Debaraj Mukherjee from Indian Institute of Integrative Medicine, C.S.I.R. Jammu, are also acknowledged for their helpful guidance.

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Authors and Affiliations

  1. School of Biotechnology, University of Jammu, Jammu, J&K, 180006, India

    Venu Sharma, Tanwi Sharma, Sanjana Kaul & Manoj K. Dhar

  2. Department of Chemistry, University of Jammu, Jammu, J&K, 180006, India

    Kamal K. Kapoor

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  1. Venu Sharma
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  2. Tanwi Sharma
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Sharma, V., Sharma, T., Kaul, S. et al. Anticancer potential of labdane diterpenoid lactone “andrographolide” and its derivatives: a semi-synthetic approach. Phytochem Rev 16, 513–526 (2017). https://doi.org/10.1007/s11101-016-9478-9

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