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Apoptosis

, Volume 22, Issue 6, pp 786–799 | Cite as

Novel Triazole linked 2-phenyl benzoxazole derivatives induce apoptosis by inhibiting miR-2, miR-13 and miR-14 function in Drosophila melanogaster

  • Tanmoy Mondal
  • A. V. S. Lavanya
  • Akash Mallick
  • Tulshiram L. Dadmala
  • Ravindra M. Kumbhare
  • Utpal Bhadra
  • Manika Pal Bhadra
Article

Abstract

Apoptosis is an important phenomenon in multi cellular organisms for maintaining tissue homeostasis and embryonic development. Defect in apoptosis leads to a number of disorders like- autoimmune disorder, immunodeficiency and cancer. 21–22 nucleotides containing micro RNAs (miRNAs/miRs) function as a crucial regulator of apoptosis alike other cellular pathways. Recently, small molecules have been identified as a potent inducer of apoptosis. In this study, we have identified novel Triazole linked 2-phenyl benzoxazole derivatives (13j and 13h) as a negative regulator of apoptosis inhibiting micro RNAs (miR-2, miR-13 and miR-14) in a well established in vivo model Drosophila melanogaster where the process of apoptosis is very similar to human apoptosis. These compounds inhibit miR-2, miR-13 and miR-14 activity at their target sites, which induce an increased caspase activity, and in turn influence the caspase dependent apoptotic pathway. These two compounds also increase the mitochondrial reactive oxygen species (ROS) level to trigger apoptotic cell death.

Keywords

Apoptosis Cancer Small molecule Micro RNA inhibitor 

Notes

Acknowledgements

We thank Stephen M. Cohen for micro RNA sensor fly stock. The work was supported by CSIR-XIIth 5 year plan project CSC-0111. TM thanks CSIR for his fellowship. All the authors thank P. Devender and Narasimha for maintaining the Drosophila facility, Y. Suresh for FACS.

Compliance with ethical standards

Conflict of interest

Authors declare no conflict of interest.

Supplementary material

10495_2017_1367_MOESM1_ESM.docx (752 kb)
Supplementary material 1 (DOCX 751 KB)

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Tanmoy Mondal
    • 1
    • 4
  • A. V. S. Lavanya
    • 1
  • Akash Mallick
    • 1
  • Tulshiram L. Dadmala
    • 2
  • Ravindra M. Kumbhare
    • 2
  • Utpal Bhadra
    • 3
  • Manika Pal Bhadra
    • 1
    • 4
  1. 1.Centre for Chemical BiologyCSIR-Indian Institute of Chemical TechnologyHyderabadIndia
  2. 2.Fluoroorganic DivisionCSIR-Indian Institute of Chemical TechnologyHyderabadIndia
  3. 3.Functional Genomics and Gene silencing GroupCSIR-Centre for Cellular and Molecular BiologyHyderabadIndia
  4. 4.Academy of Scientific and Innovative Research (AcSIR)HyderabadIndia

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