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Applied Biochemistry and Biotechnology

, Volume 176, Issue 7, pp 1996–2017 | Cite as

A Novel Approach for Overcoming Drug Resistance in Breast Cancer Chemotherapy by Targeting new Synthetic Curcumin Analogues Against Aldehyde Dehydrogenase 1 (ALDH1A1) and Glycogen Synthase Kinase-3 β (GSK-3β)

  • Rajesh Kumar KesharwaniEmail author
  • Vandana Srivastava
  • Prabhakar Singh
  • Syed Ibrahim Rizvi
  • Kuruba Adeppa
  • Krishna Misra
Article

Abstract

Breast cancer stem cells are well known to resist the traditional methods like chemo and radio therapy. Aldehyde dehydrogenase 1 (ALDHIA1) and glycogen synthase kinase-3 β (GSK-3β) are the two selected proteins for study, due to their overexpression and upregulation in breast cancer cells. Curcumin, the yellow pigment of the spice turmeric, is widely reported as an antioxidant and acts as a synergist along with traditional drugs. Under hypoxic conditions, it gets converted to free radical which causes apoptosis. Three naturally occurring curcuminoids, i.e. curcumin, demethoxycurcumin, and bisdemethoxycurcumin along with five derivatives/analogues of curcumin, viz. 4,4′-di-O-(carboxy-methyl)-curcumin, 4-O-(2-hydroxyethyl)curcumin, 4,4′-di-O-allyl-curcumin, 4,4′-di-O-(acetyl)-curcumin, and 3,3′-bisdemethylcurcumin were synthesized and evaluated for their anti-breast cancer potential by docking simulation and assessment of their antioxidant character, studied via 2, 2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS·+) radical cation scavenging assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH·) radical, and ferric reducing ability potential (FRAP) assay. A co-relation between structure and activity of curcuminoids/its analogues and derivatives has been worked out.

Keywords

Aldehyde dehydrogenase 1 Analogues Antioxidant Breast cancer Curcumin Docking Glycogen synthase kinase-3β Glide synthesis 

Notes

Acknowledgments

Rajesh Kr. Kesharwani acknowledges the Indian Council of Medical Research (ICMR), New Delhi, India, for providing senior research fellowship and wishes to thank the Director, IIIT-A, for providing computational facilities to carry out research work smoothly. Prabhakar Singh acknowledges the Council of Scientific and Industrial Research (CSIR), New Delhi, India, for providing senior research fellowship.

Conflict of Interest

The authors declare that they have no competing interests.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Rajesh Kumar Kesharwani
    • 1
    Email author
  • Vandana Srivastava
    • 2
  • Prabhakar Singh
    • 3
  • Syed Ibrahim Rizvi
    • 3
  • Kuruba Adeppa
    • 4
  • Krishna Misra
    • 1
    • 2
  1. 1.Indian Institute of Information TechnologyAllahabadIndia
  2. 2.Center of Biomedical Research, SGPGIMS CampusLucknowIndia
  3. 3.Department of BiochemistryUniversity of AllahabadAllahabadIndia
  4. 4.R & D Centre, India Pesticides LimitedLucknowIndia

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