J. Hao et al. / Bioorg. Med. Chem. Lett. 23 (2013) 2074–2077
2077
free carboxylic acid group of succinyl group was amidated with
taurine or at its -position was added an -hydroxy group, inhibi-
Supplementary data
a
L
tory activity recovered in the cell lines except for BGC-823 (11 vs 7,
17 vs 7). As a result, taurine amide 11 and malic acid ester 17 were
seven and 17 times more potent than their parent compound OA
(1) in PC3 cell line, respectively, implying that the importance of
H-bond donor group near C-3 position of OA. It seems that addition
of H-donor group to this area could enhance the cytotoxicity in
PC3, A549 and MCF-7 cell lines, which is identical with the obser-
vation in Hep G2 by Ma et al.20 Generally, N-heterocycle-contain-
ing compounds 27–32 were less potent than 1, 7, 11 or 17. For
example, the potency of compound 31 sharply descended in all
the four cancer cell lines. Lack of H-bond donor in A-ring area of
these heterocycles might be one of the possible factors for this phe-
nomenon. More general effects of N-heterocycle substitutes on
activity are hard to conclude as they differed in particular cancer
line. As for modification at C-17 position of oleanolic acid, replace-
ment of the carboxy group by the carboxymethoxycarbonyl group
leaded an overall downward trend of inhibition potency in all the
four cancer cell lines (e.g., 10 vs 19, 6 vs 16, and 4 vs 14). It has
yet to determine whether anti-cancer activity prefers small size
groups in this area.
In conclusion, 12 hydrophilic derivatives of oleanolic acid have
been synthesized and biologically evaluated for cancer cell growth
inhibition in PC3, MCF-7, A549, and BGC-823 cell lines. Several
compounds have been found to have better or comparatable
anti-cancer potency in comparison with adriamicin or oleanolic
acid. Preliminary SAR analysis shows that introduction of H-bond
donor substitution to the area near C-3 position of oleanolic acid
may benefit the potency. Highly cytotoxic compounds 11 and 17
are more interesting than OA when drug-like properties are con-
Supplementary data (details of experimental procedures and
characterisation data of synthesized compounds) associated with
this article can be found, in the online version, at http://
files and InChiKeys of the most important compounds described
in this article.
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This project was supported by the National Natural Science
Foundation (Grant No. 30672523, 90713037 and 21002125), the
‘111 Project’ from the Minisry of Education of China and the State
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