Kkurj,+journal+manager,+19 6 22plus
Kkurj,+journal+manager,+19 6 22plus
Kkurj,+journal+manager,+19 6 22plus
Abstract
Interested in chemical and biological properties of polymethoxyflavones, a series of methylated quercetin
derivatives were synthesized and characterized. Quercetin was methylated with CH3I in the presence of K2CO3/DMF,
and the products were purified by column chromatography. Three quercetin derivatives with different methyl group
numbers were isolated and the chemical structures were confirmed by IR and NMR. Along with physical character-
izations, rat prostate steroid 5α-reductase inhibition of the quercetin derivatives was measured. It was found that
methylation of quercetin lowered the inhibitory effect of the derivatives against 5α-reductase.
The chemical structures of the compounds were inhibitory effect at only 100 μM. Overall, quercetin
confirmed by IR and 1H NMR spectroscopy. 1H NMR exhibited better inhibitory activity than the methylated
spectrum of compound 2 showed two hydroxyl group peaks derivatives. Besides, increased methylation seemed to
at 5.64 (3’ position) and 12.56 (5 position) ppm. However, lower the inhibitory effect.
only one 5-hydroxyl group was found at 12.56 ppm in In this study, three quercetin derivatives were
compound 3. In the 1H NMR spectrum of compound 4, no synthesized and the inhibition effects of steroid 5α-reductase
hydroxyl group was observed and five methyl peaks were were examined.
found at the region of 3.9 ppm. In the IR spectra of com- From the comparison of structures and inhibitory
pound 2 and 3, hydroxyl groups were observed at 3490 effects of the PMFs, the flavone with more hydroxyl groups
and 3447 cm-1, respectively. The carbonyl groups of com- appears to increase the inhibitory activity. However, some
pound 2, 3 and 4 were observed at 1610, 1602 and 1624 inhibition percentages were measured over 100% at 1000
cm-1, respectively. μM concentration, and the ranges of a few data were
3.2 Steroid 5α-reductase inhibitions high. It could be poor solubility of methylated flavones or
Quercetin and three synthesized methylated more likely lower activity of the prepared steroid 5α-
quercetin derivatives were evaluated for their inhibitory reductase. Therefore, 5α-reductase inhibition test needs
activity against steroid 5α-reductase. Riboflavin was to be carried out again. Regardelss, a general tendency of
included as a positive control. As shown at Table 1, the methylation on the inhibition of 5α-reductase could be
inhibitory effects of the compounds 2 and 3 were consistent found with the limited number of data.
with large data variations. Therefore, we discuss the
Table 1. Inhibitory effect of quercetin and the methylated derivatives on rat prostate testosterone 5α-reductase
Inhibition (%)
Compound IC50 (μM)
100 μM 1000 μM
Quercetin (1) 95.6 ± 2.8 153.6 ± 44.4 16
5,3’-Dihydroxy-3,7,4’-trimethoxyflavone (2) 66.7 ± 7.6 95.4 ± 42.5 26
5-Hydroxy-3,7,3’,4’-tetramethoxyflavone (3) 36.6 ± 22.9 12.8 ± 41.3 > 1000
3,5,7,3’,4’-Pentamethoxyflavone (4) 48.2 ± 47.3 124.9 ± 3.3 110
Riboflavin 76.2 ± 6.8 96.2 ± 13.2 4.9
KKU Res. J. 2014; 19(Supplement Issue)
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