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Design, Synthesis and Biological Evaluation of Novel Analogs of Bortezomib

  • Rao, R. Janaki Rama ;
  • Rao, A.K.S. Bhujanga ;
  • Swapna, K. ;
  • Rani, B. Baby ;
  • Kumar, S. Prasanna ;
  • Awantika, S. ;
  • Murthy, Y.L.N.
  • Received : 2011.03.25
  • Accepted : 2011.07.08
  • Published : 2011.10.20

Abstract

Novel analogs of bortezomib were designed, synthesized and in vitro biological evaluation was carried out using human tumor cell lines A549 and PC3. Docking studies of these analogs of bortezomib was discussed. According to biological investigations, the inhibitors 4, 6, and 8 were found to be more potent than reference drug candidate bortezomib. A549 cell line showed significant sensitivity towards 4, 6, and 8 with $IC_{50}$ values 14.03, 18.5, and 12.4 nM, respectively, and PC3 cell line showed IC50 values 26.1, 37.0, and 21.2 nM, respectively. The $IC_{50}$ values of bortezomib in these cell lines are 27.3 nM and 42.0 nM.

Keywords

Bortezomib;human tumor cell lines;A549;PC3;$IC_{50}$ values

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