Structure-Activity Relationships of the Antitumor C5-Curcuminoid GO-Y030
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Pharmacological Evaluation
2.3. SAR of C5-Curcuminoid GO-Y030
2.3.1. Roles of the 3,5-Bismethoxymethoxy Substituent
Compound | R | GI50 (μM) *2 | |
---|---|---|---|
GO-949 | R2 = R3 = OCH2O, R6 = R7 = OCH2O | R1 = R4 = R5 = R8 = H | >50 *1 |
GO-Y030 | R2 = R4 = R6 = R8 = OCH2OMe | R1 = R3 = R5 = R7 = H | 0.3 |
GO-Y038 | R2 = R4 = R6 = R8 = OH | R1 = R3 = R5 = R7 = H | 1.5 |
GO-Y067 | R2 = R4 = R6 = R8 = OMe | R1 = R3 = R5 = R7 = H | 2.0 |
GO-Y129 | R2 = R4 = R6 = R8 = OCH2CH2OMe | R1 = R3 = R5 = R7 = H | 0.2 |
GO-Y130 | R2 = R4 = R6 = R8 = OCH2CH2OH | R1 = R3 = R5 = R7 = H | 6.4 |
GO-Y147 | R2 = R4 = R6 = R8 = OCH2OCH2CH2OMe | R1 = R3 = R5 = R7 = H | 2.0 |
GO-Y156 | R2 = R4 = OCH2OMe, R6 = R7 = OCH2O | R1 = R3 = R5 = R8 = H | 7.9 |
GO-Y164 | R1 = R4 = R5 = R8 = OCH2OMe | R2 = R3 = R6 = R7 = H | 1.7 |
2.3.2. Roles of the Central Tether Moiety
X Compound GI50 (μM) *2 | ||||
GO-Y030 | GO-Y077 | GO-Y131 | GO-Y134 | |
0.3 | 0.9 | 6.8 | 18 | |
X Compound GI50 (μM) *2 | ||||
GO-Y095 | GO-Y075 | GO-Y132 | GO-Y133 | |
0.9 | 2.1 | >50 | >50 |
2.3.3. Effect of Two Aromatic Rings
2.3.4. Effects of Introduction of Electron Withdrawing Group and Amino Group at C-2
Type 1 Analogues | ||||||
X Compound GI50 (μM) *2 | ||||||
GO-Y166 | GO-Y167 | EF-24 | GO-Y152 | GO-Y153 | ||
1.9 | 2.8 | 2.3 | 3.9 | 18 | ||
X Compound GI50 (μM) *2 | ||||||
GO-Y160 | GO-Y161 | GO-Y162 | GO-Y163 | |||
>50 | >50 | 19 | 3.6 | |||
Type 2 Analogues | ||||||
X Compound GI50 (μM) *2 | ||||||
GO-Y165 | GO-Y170 | GO-Y168 | GO-Y169 | GO-Y172 | ||
33 | 3.6 | 1.0 | 1.8 | 1.3 |
Compound | X | Chemical Shift of Cβ-H (ppm) | GI50 (μM) *2 |
---|---|---|---|
GO-Y030 | H | 7.64 | 0.3 |
GO-Y165 | CN | 8.22 | 3.3 |
GO-Y170 | F | 6.89 | 3.6 |
GO-Y168 | Cl | 7.77 | 1.0 |
GO-Y169 | Br | 7.99 | 1.8 |
3. Experimental Section
3.1. General Information
3.2. Chemical Synthesis
3.3. Cell Growth Suppression Analysis
4. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Kohyama, A.; Yamakoshi, H.; Hongo, S.; Kanoh, N.; Shibata, H.; Iwabuchi, Y. Structure-Activity Relationships of the Antitumor C5-Curcuminoid GO-Y030. Molecules 2015, 20, 15374-15391. https://doi.org/10.3390/molecules200815374
Kohyama A, Yamakoshi H, Hongo S, Kanoh N, Shibata H, Iwabuchi Y. Structure-Activity Relationships of the Antitumor C5-Curcuminoid GO-Y030. Molecules. 2015; 20(8):15374-15391. https://doi.org/10.3390/molecules200815374
Chicago/Turabian StyleKohyama, Aki, Hiroyuki Yamakoshi, Shoko Hongo, Naoki Kanoh, Hiroyuki Shibata, and Yoshiharu Iwabuchi. 2015. "Structure-Activity Relationships of the Antitumor C5-Curcuminoid GO-Y030" Molecules 20, no. 8: 15374-15391. https://doi.org/10.3390/molecules200815374