A natural product inspired tetrahydropyran collection yields mitosis modulators that synergistically target CSE1L and tubulin.
A Prins cyclization between a polymer-bound aldehyde and a homoallylic alcohol served as the key step in the synthesis of tetrahydropyran derivatives. A phenotypic screen led to the identification of compounds that inhibit mitosis (as seen by the accumulation of round cells with condensed DNA and membrane blebs). These compounds were termed tubulexins as they target the CSE1L protein and the vinca alkaloid binding site of tubulin.
Max-Planck-Institut für molekulare Physiologie, Abt. Chemische Biologie, Dortmund, Germany.
Tobias
T
Voigt
Claas
C
Gerding-Reimers
Tuyen Thi
TT
Ngoc Tran
Sabrina
S
Bergmann
Hugo
H
Lachance
Beate
B
Schölermann
Andreas
A
Brockmeyer
Petra
P
Janning
Slava
S
Ziegler
Herbert
H
Waldmann
D000818:Animals; D001665:Binding Sites; D029563:Cellular Apoptosis Susceptibility Protein / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D008938:Mitosis / Q000187:drug effects; D050258:Mitosis Modulators; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D029563:Cellular Apoptosis Susceptibility Protein; D050258:Mitosis Modulators; D011714:Pyrans; D014404:Tubulin; D050257:Tubulin Modulators