Design and synthesis of Pictet-Spengler condensation products that exhibit oncogenic-RAS synthetic lethality and induce non-apoptotic cell death.

Citation:

Skouta R, Hayano M, Shimada K, Stockwell BR. Design and synthesis of Pictet-Spengler condensation products that exhibit oncogenic-RAS synthetic lethality and induce non-apoptotic cell death. Bioorg Med Chem Lett. 2012;22 (17) :5707-13.

Date Published:

2012 Sep 1

Abstract:

A series of Pictet-Spengler condensation derivatives (tetrahydro-β-carbolines) was designed, synthesized and evaluated for lethality against a panel of seven cancer cell lines. Seven compounds (2a, 13, 20, 21, 27, 29 and 34) showed lethality in at least five cell lines. Among these, compound 27 showed a unique selectivity towards oncogenic-RAS expressing BJ-TERT/LT/ST/RAS(V12) tumor cells, compared to non-transformed BJ-TERT cells. Further investigation revealed that 27 induces cell death without activation of caspases. This represents a useful new probe of non-apoptotic cell death and oncogenic-RAS synthetic lethality.

Kenichi Shimada

Research Associate

Design and synthesis of Pictet-Spengler condensation products that exhibit oncogenic-RAS synthetic lethality and induce non-apoptotic cell death.

Citation:

Date Published:

Abstract:

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