1384274-56-9Relevant academic research and scientific papers
NOVEL CURCUMINOID-INSPIRED SYNTHETIC COMPOUNDS AS ANTI-TUMOR AGENTS
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Paragraph 0218; 0234, (2019/01/04)
Novel CUR- and CUR-BF2 compounds exhibiting anti-tumor properties are presented. CUR compounds bearing fluorinated moieties with selective fluorine introduction into the α-carbonyl moiety as well as CUR-BF2 adducts and CURs with dive
Fluoro-curcuminoids and curcuminoid-BF2adducts: Synthesis, X-ray structures, bioassay, and computational/docking study
Laali, Kenneth K.,Rathman, Benjamin M.,Bunge, Scott D.,Qi, Xin,Borosky, Gabriela L.
, p. 29 - 41 (2016/09/28)
A series of α-carbonyl fluorinated curcuminoids were synthesized by direct mono- and difluorination with Selectfluor (F-TEDA-BF4) at r.t. without using a base or additive. Ring fluorinated/trifluoromethylated curcuminoid-BF2adducts were synthesized by reaction of the corresponding benzaldehydes with acetylacetone-BF2. Decomplexation of CUR-BF2adducts under microwave irradiation gave the corresponding curcuminoids. Multinuclear NMR and X-ray analysis confirm that curcuminoids bearing fluorines or trifluoromethyl groups in the aryl rings as well as those that are monofluorinated at the active methylene position all exist as enol tautomers. The α,α-difluorination brings about significant conformational change as these curcuminoids become fixed in the 1,3-diketone configuration. The X-ray structures of CUR-BF2complexes are consistent with the formation of symmetrical adducts with equal B[sbnd]O bond distances. The anti-proliferative activity of these compounds were tested by in-vitro bioassay against several different cancer cell lines. The corresponding CUR-BF2adducts exhibited exceptionally high activities at micromolar and in some cases nanomolar concentrations that greatly surpass the activity of parent curcumin. Computational docking calculations were performed to gauge binding energies of these compounds in HER2 protein, and in 20S proteasome, for comparison with the bioassay-derived activity data.
Antitumor agents 290. Design, synthesis, and biological evaluation of new LNCaP and PC-3 cytotoxic curcumin analogs conjugated with anti-androgens
Shi, Qian,Wada, Koji,Ohkoshi, Emika,Lin, Li,Huang, Rong,Morris-Natschke, Susan L.,Goto, Masuo,Lee, Kuo-Hsiung
experimental part, p. 4020 - 4031 (2012/09/08)
In our continuing study of curcumin analogs as potential anti-prostate cancer drug candidates, 15 new curcumin analogs were designed, synthesized and evaluated for cytotoxicity against two human prostate cancer cell lines, androgen-dependent LNCaP and androgen-independent PC-3. Twelve analogs (5-12, 15, 16, 19, and 20) are conjugates of curcumin (1) or methyl curcumin (2) with a flutamide- or bicalutamide-like moiety. Two compounds (22 and 23) are C4-mono- and difluoro-substituted analogs of dimethyl curcumin (DMC, 21). Among the newly synthesized conjugates compound 15, a conjugate of 2 with a partial bicalutamide moiety, was more potent than bicalutamide alone and essentially equipotent with 1 and 2 against both prostate tumor cell lines with IC 50 values of 41.8 μM (for LNCaP) and 39.1 μM (for PC-3). A cell morphology study revealed that the cytotoxicity of curcumin analogs or curcumin-anti-androgen conjugates detected from both prostate cancer cell lines might be due to the suppression of pseudopodia formation. A molecular intrinsic fluorescence experiment showed that 1 accumulated mainly in the nuclei, while conjugate 6 was distributed in the cytosol. At the tested conditions, anti-androgens suppressed pseudopodia formation in PC-3 cells, but not in LNCaP cells. The evidence suggests that distinguishable target proteins are involved, resulting in the different outcomes toward pseudopodia suppression.
