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Synthesis and evaluation of bile acid amides of \(\alpha \)-cyanostilbenes as anticancer agents

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Abstract

A series of amino-substituted \(\alpha \)-cyanostilbene derivatives and their bile acid (cholic and deoxycholic acid) amides were designed and synthesized. A comparative study on the anticancer and antibacterial activity evaluation on the synthesized analogs was carried against the human osteosarcoma (HOS) cancer cell line, and two gram −ve (E. coli and S. typhi) and two gram \(+\)ve (B. subtilis and S. aureus) bacterial strains. All the cholic acid \(\alpha \)-cyanostilbene amides showed an \(\hbox {IC}_{50}\) in the range 2–13 \(\upmu \hbox {M}\) against human osteosarcoma cells (HOS) with the most active analog (6g) possessing an \(\hbox {IC}_{50}\) of \(2\,\upmu \hbox {M}\). One of the amino-substituted \(\alpha \)-cyanostilbene, 4e, was found to possess an \(\hbox {IC}_{50}\) of \(3\,\upmu \hbox {M}\). An increase in the number of cells at the sub-\(\hbox {G}_{1}\) phase of the cell was observed in the in vitro cell cycle analysis of two most active compounds in the series (4e, 6g) suggesting a clear indication toward induction of apoptotic cascade. With respect to antibacterial screening, amino-substituted \(\alpha \)-cyanostilbenes were found to be more active than their corresponding bile acid amides. The synthesized compounds were also subjected to in silico study to predict their physiochemical properties and drug-likeness score.

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Acknowledgements

The author RS would like to acknowledge Birla Institute of Technology and Science (BITS), Pilani, for providing additional research grant. The author DA is thankful to DST, New Delhi, for providing Senior Research Fellowship. We also like to thank central NMR facility BITS Pilani. The authors also sincerely acknowledge financial support from DST under FIST program [Project: SR/FST/CSI-270/2015] for HRMS facility.

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  1. Department of Chemistry, Birla Institute of Technology and Science, Pilani, Rajasthan, 333 031, India

    Devesh S. Agarwal & Rajeev Sakhuja

  2. Department of Biological Sciences, Birla Institute of Technology and Sciences, Pilani, Rajasthan, 333031, India

    Rajnish Prakash Singh, K. Lohitesh, Prabhat N. Jha & Rajdeep Chowdhury

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  1. Devesh S. Agarwal
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Agarwal, D.S., Singh, R.P., Lohitesh, K. et al. Synthesis and evaluation of bile acid amides of \(\alpha \)-cyanostilbenes as anticancer agents. Mol Divers 22, 305–321 (2018). https://doi.org/10.1007/s11030-017-9797-9

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