TY - JOUR
T1 - Synthesis and biological evaluation of arylphosphonium-benzoxaborole conjugates as novel anticancer agents
AU - Jonnalagadda, Sravan K.
AU - Wielenberg, Kevin
AU - Ronayne, Conor T.
AU - Jonnalagadda, Shirisha
AU - Kiprof, Paul
AU - Jonnalagadda, Subash C.
AU - Mereddy, Venkatram R.
N1 - Funding Information:
This work was supported by Whiteside Clinical Research Institute, Randy Shaver Cancer Research Community, Department of Chemistry & Biochemistry and College of Pharmacy, University of Minnesota Duluth.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/7/15
Y1 - 2020/7/15
N2 - Arylphosphonium-benzoxaborole conjugates have been synthesized as potential mitochondria targeting anticancer agents. The synthesized compounds have been tested for their effects on cell viability in various solid tumor cell lines including breast cancer 4T1 and MCF-7, pancreatic cancer MIAPaCa-2 and colorectal adenocarcinoma WiDr. Compound 6c is designated as a lead compound for further studies due to its enhanced effects on cell viability in the above-mentioned cell lines. Seahorse Xfe96 based metabolic assays reveal that the lead candidate 6c inhibits mitochondrial respiration in 4T1 and WiDr cell lines as evidenced by the reduction of mitochondrial ATP production and increase in proton leak. Epiflourescent microscopy experiments also illustrate that 6c causes significant mitochondrial fragmentation in 4T1 and WiDr cells, morphologically consistent with programmed cell death. Our current studies illustrate that arylphosphonium-benzoxaborole conjugates have potential to be further developed as anticancer agents.
AB - Arylphosphonium-benzoxaborole conjugates have been synthesized as potential mitochondria targeting anticancer agents. The synthesized compounds have been tested for their effects on cell viability in various solid tumor cell lines including breast cancer 4T1 and MCF-7, pancreatic cancer MIAPaCa-2 and colorectal adenocarcinoma WiDr. Compound 6c is designated as a lead compound for further studies due to its enhanced effects on cell viability in the above-mentioned cell lines. Seahorse Xfe96 based metabolic assays reveal that the lead candidate 6c inhibits mitochondrial respiration in 4T1 and WiDr cell lines as evidenced by the reduction of mitochondrial ATP production and increase in proton leak. Epiflourescent microscopy experiments also illustrate that 6c causes significant mitochondrial fragmentation in 4T1 and WiDr cells, morphologically consistent with programmed cell death. Our current studies illustrate that arylphosphonium-benzoxaborole conjugates have potential to be further developed as anticancer agents.
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U2 - 10.1016/j.bmcl.2020.127259
DO - 10.1016/j.bmcl.2020.127259
M3 - Article
C2 - 32527557
AN - SCOPUS:85085372341
VL - 30
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 14
M1 - 127259
ER -