Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1562-1576 |
| Number of pages | 15 |
| Journal | European Journal of Organic Chemistry |
| Volume | 2016 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Mar 1 2016 |
| Externally published | Yes |
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Keywords
- Allocolchicine
- Anticancer
- Domino reactions
- Drug design
- Fluorine
- Synthetic methods
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Organic Chemistry
Cite this
Diversity Oriented Synthesis of Allocolchicinoids with Fluoro and/or Oxygen Substituent(s) on the C-Ring from a Single Common Intermediate. / Takubo, Keita; Furutsu, Kazunori; Ide, Takafumi; Nemoto, Hiroyuki; Ueda, Yuko; Tsujikawa, Kazutake; Ikawa, Takashi; Yoshimitsu, Takehiko; Akai, Shuji.
In: European Journal of Organic Chemistry, Vol. 2016, No. 8, 01.03.2016, p. 1562-1576.Research output: Contribution to journal › Article
}
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
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
UR - http://www.scopus.com/inward/record.url?scp=84975701846&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84975701846&partnerID=8YFLogxK
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 -