Identification of novel ROS inducers: Quinone derivatives tethered to long hydrocarbon chains

Yeonsun Hong, Sandip Sengupta, Wooyoung Hur, Taebo Sim

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

We performed the first synthesis of the 17-carbon chain-tethered quinone moiety 22 (SAN5201) of irisferin A, a natural product exhibiting anticancer activity, and its derivatives. We found that 22 is a potent ROS inducer and cytotoxic agent. Compound 25 (SAN7401), the hydroquinone form of 22, induced a significant release of intracellular ROS and apoptosis (EC<inf>50</inf> = 1.3-2.6 μM) in cancer cell lines, including A549 and HCT-116. Compared with the activity of a well-known ROS inducer, piperlongumine, 22 and 25 showed stronger cytotoxicity and higher selectivity over noncancerous cells. Another hydroquinone tethering 12-carbon chain, 26 (SAN4601), generated reduced levels of ROS but showed more potent cytotoxicity (EC<inf>50</inf> = 0.8-1.6 μM) in cancer cells, although it lacked selectivity over noncancerous cells, implying that the naturally occurring 17-carbon chain is also crucial for ROS production and a selective anticancer effect. Both 25 and 26 displayed strong, equipotent activities against vemurafenib-resistant SK-Mel2 melanoma cells and p53-deficient H1299 lung cancer cells as well, demonstrating their broad therapeutic potential as anticancer agents.

Original languageEnglish
Pages (from-to)3739-3750
Number of pages12
JournalJournal of Medicinal Chemistry
Volume58
Issue number9
DOIs
Publication statusPublished - 2015 May 14

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Hydrocarbons
Carbon
Cytotoxins
Biological Products
Antineoplastic Agents
Melanoma
Lung Neoplasms
Neoplasms
benzoquinone
Apoptosis
hydroquinone
Therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Identification of novel ROS inducers : Quinone derivatives tethered to long hydrocarbon chains. / Hong, Yeonsun; Sengupta, Sandip; Hur, Wooyoung; Sim, Taebo.

In: Journal of Medicinal Chemistry, Vol. 58, No. 9, 14.05.2015, p. 3739-3750.

Research output: Contribution to journalArticle

Hong, Yeonsun ; Sengupta, Sandip ; Hur, Wooyoung ; Sim, Taebo. / Identification of novel ROS inducers : Quinone derivatives tethered to long hydrocarbon chains. In: Journal of Medicinal Chemistry. 2015 ; Vol. 58, No. 9. pp. 3739-3750.
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