Author/Authors :
Faghih Akhlaghi, Masoud Department of Medicinal Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences, Iran , Daeihamed, Marjan Department of Pharmaceutics - School of Pharmacy - Guilan University of Medical Sciences, Rasht, Iran , Ayatollahi, Abdolmajid Phytochemistry Research Center - Shahid Beheshti University of Medical Sciences, Tehran, Iran , Kobarfard, Farzad Department of Medicinal Chemistry - School of Pharmacy - Shahid Beheshti University of Medical Sciences, Iran , Ata, Athar Department 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.
Keywords :
Aryl-2-nitrovinyl , Michael acceptor , α,β-unsaturated nitro , Small molecule , Proteasome inhibitor
