Synthesis and biological evaluation of arylphosphonium-benzoxaborole conjugates as novel anticancer agents

Sravan K. Jonnalagadda; Kevin Wielenberg; Conor T. Ronayne; Shirisha Jonnalagadda; Paul Kiprof; Subash C. Jonnalagadda; Venkatram R. Mereddy

doi:10.1016/j.bmcl.2020.127259

Synthesis and biological evaluation of arylphosphonium-benzoxaborole conjugates as novel anticancer agents

Sravan K. Jonnalagadda, Kevin Wielenberg, Conor T. Ronayne, Shirisha Jonnalagadda, Paul Kiprof, Subash C. Jonnalagadda, Venkatram R. Mereddy

Chemistry & Biochemistry

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Abstract

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.

Original language	English (US)
Article number	127259
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	30
Issue number	14
DOIs	https://doi.org/10.1016/j.bmcl.2020.127259
State	Published - Jul 15 2020

Bibliographical note

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

Keywords

Benzoxaborole
Cell viability
Glycolysis stress test
Mitochondrial fragmentation
Mitochondrial stress test
Phosphonium salts

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

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abstract = "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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AU - Kiprof, Paul

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AU - Mereddy, Venkatram R.

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Synthesis and biological evaluation of arylphosphonium-benzoxaborole conjugates as novel anticancer agents

Abstract

Bibliographical note

Keywords

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UN SDGs

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