Abstract
Peptide cyclization has been recognized as capable of overcoming the shortcomings of linear peptides such as poor stability, short half-life, low selectivity and low affinity to receptors, and the modification of cyclic peptides to achieve specific activity requirements is receiving increasing attention. Hikiamide B is a cyclic pentadepsipeptide that can induce the expression of peroxisome-proliferator-activated receptor-γ (PPAR-γ). Considering that PPAR-γ can effectively regulate the expression of genes related to tumorigenesis, and is a potential tumor target, in this paper, we have prepared several Hikiamide B analogs by intramolecular photo-induced single-electron-transfer (SET) reaction to find novel antitumor drugs The stereochemistry and the in vitro antitumor activity against HepG-2 and HeLa cells were investigated. We found that the compound with stronger intramolecular hydrogen bonds (compound 2) than other compounds showed more promising antitumor activity, and the cyclic compounds present stronger bioactivity than that of their linear precursors. In vitro studies of apoptosis mechanisms and mitochondrial membrane potential following cyclopeptide 2 treat have shown that the cyclopeptide may induce apoptosis in tumor cells. Finally, in silico ADME analysis has shown the potential of compound 2 for practical application.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
