Pharmaceutical Research

, Volume 27, Issue 6, pp 1146–1158

Structure-Activity Studies on Therapeutic Potential of Thymoquinone Analogs in Pancreatic Cancer

Authors

  • Sanjeev Banerjee
    • Department of Pathology Barbara Ann Karmanos Cancer InstituteWayne State University School of Medicine
  • Asfar S. Azmi
    • Department of Pathology Barbara Ann Karmanos Cancer InstituteWayne State University School of Medicine
  • Subhash Padhye
    • D.Y.Patil University
  • Marjit W. Singh
    • Department of ChemistryIndian Institute of Technology
  • Jubaraj B. Baruah
    • Department of ChemistryIndian Institute of Technology
  • Philip A. Philip
    • Division of Hematology and Oncology, Barbara Ann Karmanos Cancer InstituteWayne State University School of Medicine
  • Fazlul H. Sarkar
    • Department of Pathology Barbara Ann Karmanos Cancer InstituteWayne State University School of Medicine
    • Division of Hematology and Oncology, Barbara Ann Karmanos Cancer InstituteWayne State University School of Medicine
Research Paper

DOI: 10.1007/s11095-010-0145-3

Cite this article as:
Banerjee, S., Azmi, A.S., Padhye, S. et al. Pharm Res (2010) 27: 1146. doi:10.1007/s11095-010-0145-3

ABSTRACT

Purpose

Pancreatic cancer (PC) is one of the deadliest of all tumors. Previously, we were the first to show that Thymoquinone (TQ) derived from black seed (Nigella sativa) oil has anti-tumor activity against PC. However, the concentration of TQ required was considered to be high to show this efficacy. Therefore, novel analogs of TQ with lower IC50 are highly desirable.

Methods

We have synthesized a series of 27 new analogs of TQ by modifications at the carbonyl sites or the benzenoid sites using single pot synthesis and tested their biological activity in PC cells.

Results

Among these compounds, TQ-2G, TQ-4A1 and TQ-5A1 (patent pending) were found to be more potent than TQ in terms of inhibition of cell growth, induction of apoptosis and modulation of transcription factor-NF-κB. We also found that our novel analogs were able to sensitize gemcitabine and oxaliplatin-induced apoptosis in MiaPaCa-2 (gemcitabine resistant) PC cells, which was associated with down-regulation of Bcl-2, Bcl-xL, survivin, XIAP, COX-2 and the associated Prostaglandin E2.

Conclusion

From our results, we conclude that three of our novel TQ analogs warrant further investigation against PC, especially in combination with conventional chemotherapeutic agents.

KEY WORDS

apoptosis pancreatic cancer thymoquinone thymoquinone analogs

Copyright information

© Springer Science+Business Media, LLC 2010