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Design, synthesis, and biological evaluation of new 12-substituted-14-deoxy-andrographolide derivatives as apoptosis inducers

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Abstract

Andrographolide (1), the major labdane diterpenoidal constituent of Andrographis paniculata Wall, has been found to be majorly responsible for the medicinal uses of the plant particularly anti-cancer properties. In our previous work, we have found 3,19-diacetyl-12-phenylthio-14-deoxy-andrographolide (3g), a semi-synthetic derivative of Andrographolide to be one of the most potent compounds exhibiting cytotoxic activity against a number of human cancer cell lines particularly HCT-116 cell line. In this work, we report the effect of 3g on cell cycle arrest and its apoptosis inducing potential on HCT-116 cell line. In addition, we also report the synthesis of some new 3,19-diacetyl-C-12-substituted-14-deoxy-andrographolide derivatives 3a–f, their cytotoxic effects on colon cancer cells (HCT-116), and the mechanistic studies of the active analogue 3c. Encouragingly, we have also found that the compounds 3c and 3g were observed to be non-toxic (IC50 > 250 μM) to baby hamster kidney (BHK-21) normal cells.

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Acknowledgements

Authors S.G.S.K., S.N., and N.R.G. would like to express their deep sense of gratitude to the Founder Chancellor, Bhagawan Sri Sathya Sai Baba for His constant inspiration and guidance throughout the work. Authors S.N. and N.R.G. thank Council of Scientific and Industrial Research (CSIR) for the financial assistance (No.02(0304)/17/EMR-II dated 5-5-2017). A.B. and S.K. thank Regional Centre for Biotechnology for intramural funding.

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Correspondence to Nageswara Rao Golakoti.

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Kandanur, S.G.S., Kundu, S., Cadena, C. et al. Design, synthesis, and biological evaluation of new 12-substituted-14-deoxy-andrographolide derivatives as apoptosis inducers. Chem. Pap. 73, 1669–1675 (2019). https://doi.org/10.1007/s11696-019-00718-9

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