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Synthesis and anti-inflammatory activity of some novel pyrimidine hybrids of myrrhanone A, a bicyclic triterpene of Commiphora mukul gum resin

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Abstract

Myrrhanone A (5S,8R,9R,10R)-3-oxo-8,30-dihydroxypolypoda-13E,17E,21E-triene), a bicyclic triterpene isolated from guggul (Commiphora mukul Hook) gum resin, was found to be a very useful bioactive natural scaffold. The aim of this work is to carry out chemical transformations on myrrhanone A to synthesize some novel pyrimidine hybrids and investigate their anti-inflammatory activity. In vitro PMA/LPS activated human monocyte U937 cells were used to screen the anti-inflammatory activity of the compounds. Interestingly, most of the synthesized hybrids have shown higher anti-inflammatory activity than the parent molecule. Especially, methyl-, nitro-, bromo-, and difluoro-substituted analogues have shown promising inhibitory activity on TNF-α and IL-1β expression at 10 µM concentrations. Most significantly, the difluoro-substituted analogue (IC50: 3.22 ± 0.44 μM for TNF-α, 9.04 ± 1.92 μM for IL-1β) exhibited potent anti-inflammatory activity when compared to the parent myrrhanone A (IC50: 20.87 ± 3.01 μM for TNF-α, 14.10 ± 1.69 μM for IL-1β).

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Acknowledgements

We are thankful to Director, CSIR-IICT for support and encouragement. We are also thankful to CSIR, India, for providing fellowship to MC.

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Authors and Affiliations

  1. Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India

    Chandrashekhar Madasu & Venkata Mallavadhani Uppuluri

  2. Department of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India

    Sagarika Gudem & Ramakrishna Sistla

  3. Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India

    Chandrashekhar Madasu & Venkata Mallavadhani Uppuluri

Authors
  1. Chandrashekhar Madasu
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  2. Sagarika Gudem
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  3. Ramakrishna Sistla
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  4. Venkata Mallavadhani Uppuluri
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Corresponding author

Correspondence to Venkata Mallavadhani Uppuluri.

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Madasu, C., Gudem, S., Sistla, R. et al. Synthesis and anti-inflammatory activity of some novel pyrimidine hybrids of myrrhanone A, a bicyclic triterpene of Commiphora mukul gum resin. Monatsh Chem 148, 2183–2193 (2017). https://doi.org/10.1007/s00706-017-2024-7

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  • DOI: https://doi.org/10.1007/s00706-017-2024-7

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