Synthesis and biological evaluation of novel 2-alkoxycarbonylallylester phosphonium derivatives as potential anticancer agents. (1st August 2021)

• Record Type: Journal Article
• Authors: Gardner, Zachary S.; Schumacher, Tanner J.; Ronayne, Conor T.; Kumpati, Greeshma P.; Williams, Michael J.; Yoshimura, Akira; Palle, Hithardha; Mani, Chinnadurai; Rumbley, Jon; Mereddy, Venkatram R.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 45(2021)
• Publication Date: 2021-08-01
• Subjects: Phosphonium derivatives -- Baylis-Hillman reaction -- Anticancer agent -- MTT and SRB assay -- MitoStress test; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2021.128136
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Several phosphonium derivatives have been synthesized from Baylis-Hillman (BH) reaction derived allyl bromides and aryl phosphines as mitochondria targeting anticancer agents. In vitro cell proliferation inhibition studies on various solid tumor cell lines indicate that most of the compounds exhibit IC50 values in µM concentrations. Further studies reveal that β-substituted BH bromide derived phosphonium derivatives enhance the biological activity to low µM IC50 values. In vitro metabolic studies show that the lead candidate compound 16 inhibits the production of mitochondrial ATP, increases the proton leak within the mitochondrial membrane and abolishes the spare respiratory capacity in a concentration dependent manner.