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http://dx.doi.org/10.5012/jkcs.2011.55.5.765

Design, Synthesis and Biological Evaluation of Novel Analogs of Bortezomib  

Rao, R. Janaki Rama (Natco Research Centre, Natco Pharma Ltd.)
Rao, A.K.S. Bhujanga (Natco Research Centre, Natco Pharma Ltd.)
Swapna, K. (Natco Research Centre, Natco Pharma Ltd.)
Rani, B. Baby (Natco Research Centre, Natco Pharma Ltd.)
Kumar, S. Prasanna (Natco Research Centre, Natco Pharma Ltd.)
Awantika, S. (Natco Research Centre, Natco Pharma Ltd.)
Murthy, Y.L.N. (Department of Organic Chemistry, Andhra University)
Publication Information
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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