Evaluation of cancer-preventive activity and structure–activity relationships of 3-demethylubiquinone Q2, isolated from the ascidian Aplidium glabrum, and its synthetic analogs
Fedorov, S.N.; Shubina, L.K.; Balaneva, N.N.; Bode, A.M.; Stonik, V.A.; Dong, Z. (2006). Evaluation of cancer-preventive activity and structure–activity relationships of 3-demethylubiquinone Q2, isolated from the ascidian Aplidium glabrum, and its synthetic analogs. Pharmaceutical Research 23(1): 70-81. https://dx.doi.org/10.1007/s11095-005-8813-4
In: Pharmaceutical Research. SPRINGER/PLENUM PUBLISHERS: New York. ISSN 0724-8741; e-ISSN 1573-904X, meer
|   |
| Trefwoord |
|
| Author keywords |
marine prenylated quinones; cancer prevention; apoptosis; nuclear factor; structure-activity relationship |
| Auteurs | | Top |
- Fedorov, S.N.
- Shubina, L.K.
- Balaneva, N.N.
|
- Bode, A.M.
- Stonik, V.A.
- Dong, Z.
|
|
| Abstract |
PURPOSE:3-Demethylubiquinone Q2 was isolated from the ascidian Aplidium glabrum. The cancer-preventive properties and the structure-activity relationship for 3-demethylubiquinone Q2 and 12 of its synthetic analogs are reported.METHODS:Compounds, having one or several di- or triprenyl substitutions and quinone moieties with methoxyls in different positions, were synthesized. The cancer-preventive properties of compounds and were tested in JB6 Cl41 mouse skin cells, using a variety of assessments, including the methanethiosulfonate (MTS) assay, flow cytometry, and soft agar assay. Statistical nonparametric methods were used to confirm statistical significance.RESULTS:All quinones tested were shown to inhibit JB6 Cl41 cell transformation, to induce apoptosis, AP-1, and NF-kappaB activity, and to inhibit p53 activity. The most promising effects were indicated for compounds containing two isoprene units in a side chain and a methoxyl group at the para-position to a polyprenyl substitution.CONCLUSIONS:Quinones and demonstrated cancer-preventive activity in JB6 Cl41 cells, which may be attributed to the induction of p53-independent apoptosis. These activities depended on the length of side chains and on the positions of the methoxyl groups in the quinone part of the molecule. |
|
