Inhibition of mitochondrial metabolism by (−)-jerantinine A: synthesis and biological studies in triple-negative breast cancer cells†
Timothy L.
Gialelis, 
‡a
Zifei
Wang,
‡b
Joshua A.
Homer,
‡b
Wen-Hsuan
Yang,
‡b
Taemoon
Chung,
‡b
Qingting
Hu,
bc
Christopher J.
Smedley,
a
Nitin J.
Pawar,
b
Nitinkumar S.
Upadhyay,
b
David A.
Tuveson,
b
Scott K.
Lyons,
b
Michael J.
Lukey
*b
and
John E.
Moses
*b
‡a
Zifei
Wang,
‡b
Joshua A.
Homer,
‡b
Wen-Hsuan
Yang,
‡b
Taemoon
Chung,
‡b
Qingting
Hu,
bc
Christopher J.
Smedley,
a
Nitin J.
Pawar,
b
Nitinkumar S.
Upadhyay,
b
David A.
Tuveson,
b
Scott K.
Lyons,
b
Michael J.
Lukey
*b
and
John E.
Moses
*b
Abstract
A concise semi-synthesis of the Aspidosperma alkaloids, (−)-jerantinine A and (−)-melodinine P, and derivatives thereof, is reported. The novel compounds were shown to have potent activity against MDA-MB-231 triple-negative breast cancer cells. Furthermore, unbiased metabolomics and live cell reporter assays reveal (−)-jerantinine A alters cellular redox metabolism and induces oxidative stress that coincides with cell cycle arrest.
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