Design, Synthesis and Biological Evaluation of Novel Analogs of Bortezomib
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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 IC50 values 14.03, 18.5, and 12.4 nM, respectively, and PC3 cell line showed IC_(50) 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.
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 IC50 values 14.03, 18.5, and 12.4 nM, respectively, and PC3 cell line showed IC_(50) 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.
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