TY - JOUR
T1 - Comparison of the biological properties of several marine sponge-derived sesquiterpenoid quinones
AU - Motti, Cherie A.
AU - Bourguet-Kondracki, Marie Lise
AU - Longeon, Arlette
AU - Doyle, Jason R.
AU - Llewellyn, Lyndon E.
AU - Tapiolas, Dianne M.
AU - Yin, Ping
PY - 2007/7
Y1 - 2007/7
N2 - Eight naturally occurring marine-sponge derived sesquiterpenoid quinones were evaluated as potential inhibitors of pyruvate phosphate dikinase (PPDK), a C4 plant regulatory enzyme. Of these, the hydroxyquinones ilimaquinone, ethylsmenoquinone and smenoquinone inhibited PPDK activity with IC50's (reported with 95% confidence intervals) of 285.4 (256.4 - 317.7), 316.2 (279.2 - 358.1) and 556.0 (505.9 - 611.0) μM, respectively, as well as being phytotoxic to the C4 plant Digitaria ciliaris. The potential anti-inflammatory activity of these compounds, using bee venom phospholipase A2 (PLA2), was also evaluated. Ethylsmenoquinone, smenospongiarine, smenospongidine and ilimaquinone inhibited PLA2 activity (% inhibition of 73.2 ± 4.8 at 269 μM, 61.5 ± 6.1 at 242 μM, 41.0 ± 0.6 at 224 μM and 36.4 ± 8.2 at 279 μM, respectively). SAR analyses indicate that a hydroxyquinone functionality and a short, hydroxide/alkoxide side-chain at C-20 is preferred for inhibition of PPDK activity, and that a larger amine side-chain at C-20 is tolerated for PLA2 inhibitory activity.
AB - Eight naturally occurring marine-sponge derived sesquiterpenoid quinones were evaluated as potential inhibitors of pyruvate phosphate dikinase (PPDK), a C4 plant regulatory enzyme. Of these, the hydroxyquinones ilimaquinone, ethylsmenoquinone and smenoquinone inhibited PPDK activity with IC50's (reported with 95% confidence intervals) of 285.4 (256.4 - 317.7), 316.2 (279.2 - 358.1) and 556.0 (505.9 - 611.0) μM, respectively, as well as being phytotoxic to the C4 plant Digitaria ciliaris. The potential anti-inflammatory activity of these compounds, using bee venom phospholipase A2 (PLA2), was also evaluated. Ethylsmenoquinone, smenospongiarine, smenospongidine and ilimaquinone inhibited PLA2 activity (% inhibition of 73.2 ± 4.8 at 269 μM, 61.5 ± 6.1 at 242 μM, 41.0 ± 0.6 at 224 μM and 36.4 ± 8.2 at 279 μM, respectively). SAR analyses indicate that a hydroxyquinone functionality and a short, hydroxide/alkoxide side-chain at C-20 is preferred for inhibition of PPDK activity, and that a larger amine side-chain at C-20 is tolerated for PLA2 inhibitory activity.
UR - http://www.scopus.com/inward/record.url?scp=34547626053&partnerID=8YFLogxK
U2 - 10.3390/12071376
DO - 10.3390/12071376
M3 - Article
C2 - 17909493
AN - SCOPUS:34547626053
SN - 1420-3049
VL - 12
SP - 1376
EP - 1388
JO - Molecules
JF - Molecules
IS - 7
ER -