Design, synthesis, and biological assessment of prodrugs for nitroreductase-based HSP90 inhibitor BIIB021: exploring their potential as anticancer agents

doi:10.5246/jcps.2024.01.002

Abstract

Abstract:

A series of prodrugs based on BIIB021, designed for nitroreductase (NTR), were synthesized and tested in vitro for their cytotoxic effects as potential anticancer agents. The results revealed that compounds 1c and 2c exhibited promising antitumor activity, with IC₅₀ values of 0.72 and 1.12 μM, respectively. Notably, both compounds demonstrated lower toxicity to normal WI-38 cells compared to the positive control BIIB021 (IC₅₀= 495.51 and 570.27 μM vs. 261 μM). Cell cycle analysis indicated that both compounds induced cell cycle arrest in the G2/M phase, accompanied by a concomitant decrease in the population of the G0/G1 phase in HeLa cells, ultimately leading to apoptosis. These preliminary findings suggested that compounds 1c and 2c held the potential to serve as promising lead compounds for further structural optimization and in vivo validation studies.

Key words: Heat shock protein 90, BIIB021, NTR, Nitro benzamides

Supporting:

Zhengrong Wu, Qinjian Xie, Peng Jing, Tianfeng Zhang, Jiaxi Han, Dian He. Design, synthesis, and biological assessment of prodrugs for nitroreductase-based HSP90 inhibitor BIIB021: exploring their potential as anticancer agents[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(1): 15-25.

Figures/Tables 5

References 33

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