TY - JOUR
T1 - Diversity Oriented Synthesis of Allocolchicinoids with Fluoro and/or Oxygen Substituent(s) on the C-Ring from a Single Common Intermediate
AU - Takubo, Keita
AU - Furutsu, Kazunori
AU - Ide, Takafumi
AU - Nemoto, Hiroyuki
AU - Ueda, Yuko
AU - Tsujikawa, Kazutake
AU - Ikawa, Takashi
AU - Yoshimitsu, Takehiko
AU - Akai, Shuji
N1 - Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - Allocolchicinoids, with a distinct polyoxygenated dibenzocycloheptane skeleton, attract much attention as potential candidate anticancer drugs. In this study, eight C-ring fluorinated analogues of allocolchicinoids, seven C-ring oxygen-substituted analogues, and known compounds N-acetylcolchinol and NSC 51046 were synthesized as racemates from a single common intermediate by using either the deoxyfluorination/migration domino reaction or acid-promoted migration as the key step. Among the products obtained, some of the fluorinated derivatives strongly inhibited the growth of prostate DU145 and pancreas Panc 1 cancer cell lines with efficacy comparable to or better than those of N-acetylcolchinol and NSC 51046. They were also less toxic against a non-cancerous cell line than the known compounds were. Eight C-ring fluorinated analogues of allocolchicinoids, seven C-ring oxygen-substituted analogues, and known compounds N-acetylcolchinol and NSC 51046 were synthesized from a single common intermediate by using either the deoxyfluorination/migration domino reaction or acid-promoted migration as the key step. Some fluorinated compounds showed high cytotoxicity against prostate cancer cells.
AB - Allocolchicinoids, with a distinct polyoxygenated dibenzocycloheptane skeleton, attract much attention as potential candidate anticancer drugs. In this study, eight C-ring fluorinated analogues of allocolchicinoids, seven C-ring oxygen-substituted analogues, and known compounds N-acetylcolchinol and NSC 51046 were synthesized as racemates from a single common intermediate by using either the deoxyfluorination/migration domino reaction or acid-promoted migration as the key step. Among the products obtained, some of the fluorinated derivatives strongly inhibited the growth of prostate DU145 and pancreas Panc 1 cancer cell lines with efficacy comparable to or better than those of N-acetylcolchinol and NSC 51046. They were also less toxic against a non-cancerous cell line than the known compounds were. Eight C-ring fluorinated analogues of allocolchicinoids, seven C-ring oxygen-substituted analogues, and known compounds N-acetylcolchinol and NSC 51046 were synthesized from a single common intermediate by using either the deoxyfluorination/migration domino reaction or acid-promoted migration as the key step. Some fluorinated compounds showed high cytotoxicity against prostate cancer cells.
KW - Allocolchicine
KW - Anticancer
KW - Domino reactions
KW - Drug design
KW - Fluorine
KW - Synthetic methods
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U2 - 10.1002/ejoc.201501624
DO - 10.1002/ejoc.201501624
M3 - Article
AN - SCOPUS:84975701846
VL - 2016
SP - 1562
EP - 1576
JO - Annalen der Pharmacie
JF - Annalen der Pharmacie
SN - 0075-4617
IS - 8
ER -