Populene D Analogues: Design, Concise Synthesis and Antiproliferative Activity
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis of Populene D Analogues
Entry | Homoallylic alcohols 1a–d | Products 2a–e (yield) |
---|---|---|
1 | ||
2 | ||
3 | ||
4 |
Entry | Substrates 2a–d | Products 3a–e (yield) |
---|---|---|
1 | 2a | |
2 | 2b | |
3 | 2c | |
4 | 2d | |
5 | 2d |
2.2. Antiproliferative Activity of Populene D Analogues
Cell lines a | Doxorubicine b | 2a | 2b | 2c | 2d | 3a | 3b | 3c | 3d | 3e |
---|---|---|---|---|---|---|---|---|---|---|
U251 | 0.062 | 25.0 | 24.6 | 25.0 | >250 | >250 | 46.3 | 27.8 | 23.1 | 19.6 |
MCF-7 | 0.21 | 25.0 | 23.2 | 25.0 | 38.8 | >250 | 107.8 | 24.7 | 24.6 | 5.5 |
NCI-ADR/RES | 1.3 | 25.0 | 26.8 | 25.0 | 100.7 | >250 | >250 | 25.0 | 5.2 | 5.7 |
786-0 | 0.04 | 25.0 | 25.5 | 25.0 | 45.8 | 37.3 | 36.8 | 24.6 | 24.1 | 5.6 |
NCI-H460 | <0.025 | N.T. | N.T. | N.T. | N.T. | >250 | 41.4 | 24.2 | 45.1 | 17.4 |
PC-3 | 0.27 | 25.0 | 27.0 | 25.0 | 71.4 | >250 | >250 | 24.5 | N.T. | N.T. |
OVCAR-3 | 0.26 | 25.0 | 24.5 | 25.0 | 193.4 | >250 | >250 | 1.8 | 24.3 | 3.9 |
HT-29 | 0.22 | 25.0 | 6.6 | 25.0 | 23.1 | >250 | 78.4 | 22.9 | 6.0 | 19.5 |
K-562 | 0.4 | 3.1 | 9.6 | 25.0 | 84.6 | >250 | 41.2 | 8.7 | N.T. | N.T. |
HaCat | 0.23 | 25.0 | 26.1 | 25.0 | >250 | >250 | >250 | 3.6 | 4.2 | 4.2 |
Mean logGI50c, d | −0.78 P | 1.17 W | 1.18 W | 1.21 W | >1.70 I | >2.31 I | >1.95 I | 1.22 W | 1.24 W | 0.95 M |
Cell lines a | Doxorubicine b | 2a | 2b | 2c | 2d | 3a | 3b | 3c | 3d | 3e |
---|---|---|---|---|---|---|---|---|---|---|
U251 | 1.1 | 52.0 | 53.5 | 40.0 | >250 | >250 | >250 | 67.9 | 45.9 | 28.4 |
MCF-7 | 8.8 | 51.3 | 46.9 | 45.3 | >250 | >250 | >250 | 45.0 | 58.2 | 41.6 |
NCI-ADR/RES | 25.0 | 83.5 | 104.4 | 66.3 | >250 | >250 | >250 | 199.5 | 37.6 | >250 |
786-0 | 0.62 | 50.6 | 44.0 | 36.1 | >250 | >250 | >250 | 43.0 | 47.8 | 19.4 |
NCI-H460 | 0.025 | N.T. | N.T. | N.T. | N.T. | >250 | >250 | 45.9 | >250 | >250 |
PC-3 | 4.4 | 64.6 | 41.4 | 69.2 | >250 | >250 | >250 | 51.8 | N.T. | N.T. |
OVCAR-3 | 3.9 | 52.3 | 56.2 | 67.0 | >250 | >250 | >250 | 31.5 | 69.9 | 34.4 |
HT-29 | 25.0 | 39.1 | 33.0 | 41.8 | >250 | >250 | >250 | 53.3 | 32.3 | 39.0 |
K-562 | 25.0 | >250 | >250 | 128.1 | >250 | >250 | >250 | 39.2 | N.T. | N.T. |
HaCat | 0.67 | 66.9 | 54.4 | 32.0 | >250 | >250 | >250 | >250 | 160.7 | >250 |
3. Experimental
3.1. General
3.2. General Procedure for Prins Cyclizations
3.3. General Procedure for the Deprotections of 3a–d
3.4. Antiproliferative Assays
4. Conclusions
Supplementary Materials
Acknowledgments
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Reddy, K.R.K.K.; Longato, G.B.; Carvalho, J.E.d.; Ruiz, A.L.T.G.; Silva, L.F., Jr. Populene D Analogues: Design, Concise Synthesis and Antiproliferative Activity. Molecules 2012, 17, 9621-9630. https://doi.org/10.3390/molecules17089621
Reddy KRKK, Longato GB, Carvalho JEd, Ruiz ALTG, Silva LF Jr. Populene D Analogues: Design, Concise Synthesis and Antiproliferative Activity. Molecules. 2012; 17(8):9621-9630. https://doi.org/10.3390/molecules17089621
Chicago/Turabian StyleReddy, Kachi R. Kishore Kumar, Giovanna B. Longato, João E. de Carvalho, Ana L. T. G. Ruiz, and Luiz F. Silva, Jr. 2012. "Populene D Analogues: Design, Concise Synthesis and Antiproliferative Activity" Molecules 17, no. 8: 9621-9630. https://doi.org/10.3390/molecules17089621