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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Med+Chem
2015 ; 58
(11
): 4713-26
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Structure-Activity Relationship and Pharmacokinetic Studies of
1,5-Diheteroarylpenta-1,4-dien-3-ones: A Class of Promising Curcumin-Based
Anticancer Agents
#MMPMID25961334
Wang R
; Chen C
; Zhang X
; Zhang C
; Zhong Q
; Chen G
; Zhang Q
; Zheng S
; Wang G
; Chen QH
J Med Chem
2015[Jun]; 58
(11
): 4713-26
PMID25961334
show ga
Forty-three 1,5-diheteroaryl-1,4-pentadien-3-ones were designed as potential
curcumin mimics, structurally featuring a central five-carbon dienone linker and
two identical nitrogen-containing aromatic rings. They were synthesized using a
Horner-Wadsworth-Emmons reaction as the critical step and evaluated for their
cytotoxicity and antiproliferative activities toward both androgen-insensitive
and androgen-sensitive prostate cancer cell lines and an aggressive cervical
cancer cell line. Most of the synthesized compounds showed distinctly better in
vitro potency than curcumin in the four cancer cell lines. The structure-activity
data acquired from the study validated
(1E,4E)-1,5-dihereroaryl-1,4-pentadien-3-ones as an excellent scaffold for
in-depth development for clinical treatment of prostate and cervical cancers.
1-Alkyl-1H-imidazol-2-yl, ortho pyridyl, 1-alkyl-1H-benzo[d]imidazole-2-yl,
4-bromo-1-methyl-1H-pyrazol-3-yl, thiazol-2-yl, and
2-methyl-4-(trifluoromethyl)thiazol-5-yl were identified as optimal
heteroaromatic rings for the promising in vitro potency.
(1E,4E)-1,5-Bis(2-methyl-4-(trifluoromethyl)thiazol-5-yl)penta-1,4-dien-3-one,
featuring thiazole rings and trifluoromethyl groups, was established as the
optimal lead compound because of its good in vitro potency and attractive in vivo
pharmacokinetic profiles.