Faghih Akhlaghi, M., Daeihamed, M., Ayatollahi, S., Kobarfard, F., Ata, A. (2018). Design, Synthesis and Evaluation of Substituted Aryl-2-Nitrovinyl Derivatives as Small Molecules Proteasome Inhibitors. Iranian Journal of Pharmaceutical Research, 17(3), 906-916. doi: 10.22037/ijpr.2018.2270
Masoud Faghih Akhlaghi; Marjan Daeihamed; Seyed Abdolmajid Ayatollahi; Farzad Kobarfard; Athar Ata. "Design, Synthesis and Evaluation of Substituted Aryl-2-Nitrovinyl Derivatives as Small Molecules Proteasome Inhibitors". Iranian Journal of Pharmaceutical Research, 17, 3, 2018, 906-916. doi: 10.22037/ijpr.2018.2270
Faghih Akhlaghi, M., Daeihamed, M., Ayatollahi, S., Kobarfard, F., Ata, A. (2018). 'Design, Synthesis and Evaluation of Substituted Aryl-2-Nitrovinyl Derivatives as Small Molecules Proteasome Inhibitors', Iranian Journal of Pharmaceutical Research, 17(3), pp. 906-916. doi: 10.22037/ijpr.2018.2270
Faghih Akhlaghi, M., Daeihamed, M., Ayatollahi, S., Kobarfard, F., Ata, A. Design, Synthesis and Evaluation of Substituted Aryl-2-Nitrovinyl Derivatives as Small Molecules Proteasome Inhibitors. Iranian Journal of Pharmaceutical Research, 2018; 17(3): 906-916. doi: 10.22037/ijpr.2018.2270
Design, Synthesis and Evaluation of Substituted Aryl-2-Nitrovinyl Derivatives as Small Molecules Proteasome Inhibitors
1Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Iran.
2Department of Pharmaceutics, School of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran.
3Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4Department of Chemistry, Richardson College of the Environmental Science Complex, The University of Winnipeg, Winnipeg, Canada.
Abstract
Based on the existing structure activity relationship for proteasome inhibitors, a number of substituted aryl-2-nitrovinyl derivatives have been synthesized as Michael acceptor and their cytotoxicity and proteasome inhibitory effects were evaluated on two cancer cell lines. Compound 2d exhibited IC50 values of 0.71 and 17.79 μM comparable to bortezomib against MCF-7 and PC-3, respectively. The results show that the electronic properties and steric hindrance can affect the interaction of these small molecules with their receptor at the active site of the enzyme while the presence of CH2OH group on α-carbon of Michael acceptor is favorable, and para substitution of OMe on phenyl ring of β-carbon can increase the inhibitory potencies. Molecular docking studies confirm our experimental findings about mode of binding of our compounds with 20S proteasome.
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