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 language | English |
|---|---|
| Pages (from-to) | 3739-3750 |
| Number of pages | 12 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 58 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2015 May 14 |
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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 journal › Article
}
TY - JOUR
T1 - Identification of novel ROS inducers
T2 - Quinone derivatives tethered to long hydrocarbon chains
AU - Hong, Yeonsun
AU - Sengupta, Sandip
AU - Hur, Wooyoung
AU - Sim, Taebo
PY - 2015/5/14
Y1 - 2015/5/14
N2 - 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 (EC50 = 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 (EC50 = 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.
AB - 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 (EC50 = 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 (EC50 = 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.
UR - http://www.scopus.com/inward/record.url?scp=84929485472&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84929485472&partnerID=8YFLogxK
U2 - 10.1021/jm501846y
DO - 10.1021/jm501846y
M3 - Article
C2 - 25826398
AN - SCOPUS:84929485472
VL - 58
SP - 3739
EP - 3750
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 9
ER -