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Isolation, structural modification of macrophin from endophytic fungus Phoma macrostoma and their cytotoxic potential

  • Yedukondalu Nalli
  • Palak Arora
  • Sameer Khan
  • Fayaz Malik
  • Syed Riyaz-Ul-Hassan
  • Vivek Gupta
  • Asif AliEmail author
Original Research
  • 36 Downloads

Abstract

Four known metabolites, macrophin (1), rosellisin (2), 2-(2-hydroxy-5-6-methoxy-3-methylene-1,4-benzodioxin-2(3H)-one (3), and methoxyphenoxyacrylic acid (4) were isolated, for the first time, from an endophytic fungus, Phoma macrostoma inhabiting the inner tissue of medicinal plant Glycyrrhiza glabra Linn. Their structures were characterized by comparison of their NMR data with literature data, and X-ray diffraction data of macrophin (1) as described herein for the first time. The compounds (14) were evaluated for their growth-inhibitory activities against a panel of cancer cell lines. Of these substances, macrophin (1) showed prominent cytotoxic activity against the MDA-MB-231, T47D, MCF-7, and MIAPaCa-2 cancer-cell lines with IC50 values of 14.8, 8.12, 13.0, and 0.9 μM, respectively. This biological significance has prompted us to generate a series of five acylated analogs (1a–1e) of 1 to conduct structure–activity relationship (SAR) study. The result illustrates all the analogues (1a–1e) were more potent than 1 against MDMB-231 and MIAPaCa-2 cancer cell lines. The compound 1d, an n-butanoyl substituent, has been proven to be three-fold more potent than 1 with IC50 values of 0.3 and 3.7 µM against MIAPaCa-2 and MDMB-231 cell lines, respectively.

Keywords

Phoma macrostoma Isolation Macrophine Semi-synthesis Cytotoxic activities 

Notes

Acknowledgements

PA is supported by the Department of Science and Technology, New Delhi, India through INSPIRE Senior Research Fellowship. PA and SK acknowledge AcSIR for their enrollment in the Ph.D. program. The authors would like to acknowledge the Ministry of AYUSH (New Delhi) for providing financial support for the work of YN (Z.28015/229/2015-HCP EMR). The article bears the institutional manuscript no. IIIM/2271/2018.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2018_2281_MOESM1_ESM.docx (6.9 mb)
Supporting information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Yedukondalu Nalli
    • 1
  • Palak Arora
    • 2
    • 3
  • Sameer Khan
    • 3
    • 4
  • Fayaz Malik
    • 3
    • 4
  • Syed Riyaz-Ul-Hassan
    • 2
    • 3
  • Vivek Gupta
    • 5
  • Asif Ali
    • 1
    • 2
    Email author
  1. 1.Natural Product Chemistry DivisionCSIR-Indian Institute of Integrative MedicineJammuIndia
  2. 2.Microbial Biotechnology DivisionCSIR-Indian Institute of Integrative MedicineJammuIndia
  3. 3.Academy of Scientific and Innovative ResearchCSIR-Indian Institute of Integrative MedicineJammuIndia
  4. 4.Pharmacology DivisionCSIR-Indian Institute of Integrative MedicineJammuIndia
  5. 5.Post-Graduate Department of Physics & ElectronicsUniversity of JammuJammuIndia

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