Chemistry Reference
In-Depth Information
O
O
O
O
O
O
R
O
O
O
R
G4
Neo-tanshinlactone, R = CH
3
G5
R = CH
2
CH
3
G1
Tanshinone I
G2
Tanshinone II-A, R
=
H
G3
Sodium tanshinone II-A
sulfonate, R
=
SO
3
Na
Figure 14.7
Structures of tanshinlactones and neo-tanshinlactone.
exhibits hypotensive effects, causes coronary artery vasodilation, and inhibits
platelet aggregation. Accordingly, it should not be used in combination with
warfarin. Tanshen also has been applied for hemorrhage, dysmenorrhea, miscar-
riage, swelling, inflammation, chronic hepatitis, and insomnia (74, 75). Clinically
available preparations of a
S. miltiorrhiza
/
Dalbergia odorifera
mixture may have
potential as an anti-anginal drug (76).
Tanshinone diterpenoids, including tanshinone I (
G1
) and tanshinone IIA (
G2
),
are bioactive compounds from
S. miltiorrhiza
(77). Sodium tanshinone sulfate
(
G3
) is a water-soluble derivative of
G2
, is used clinically to treat angina pectoris
and myocardial infarction, and exhibits strong membrane-stabilizing effects on
red blood corpuscles. In addition, novel
seco
-abietane rearranged diterpenoids
were isolated recently from this species (78).
Other studies have shown that
S. miltiorrhiza
exerts clear cytotoxic effects
and strongly inhibits the proliferation of liver cancer cells (79). Various tanshi-
nones were tested in SAR studies against several human tumor cells, namely
nasopharyngeal (KB), cervical (Hela), colon (Colon 205), and laryngeal (Hep-2)
cell systems (74, 75).
Neo-tanshinlactone (
G4
), also originally isolated from Tanshen, has a unique
and different structure compared with other compounds from
S. miltiorrhiza
Bunge. Preliminary studies of this compound showed unique specific activity
against the MCF-7 breast cancer cell line but insignificant activity against other
cell lines in the tested panel. Extended bioassay studies showed that
G4
is quite
active against estrogen receptor positive (ER+) human breast cancer cell lines
(MCF-7 and ZR-75-1) but inactive against ER negative (ER-) human breast can-
cer lines (MDA MB-231 and HS 587-T) (80). This finding is significant because
more than 60% of breast cancer cases in postmenopausal women are ER+. Com-
pared with the breast cancer drug tamoxifen citrate,
G4
was 10-fold more potent
and 20-fold more selective against two ER+ cell lines (80). It also was potent
against an ER- cell line that overexpresses the protein HER2+, which plays a key
role in regulating cell growth and affects 25-30% of breast cancer patients (80).
These results indicate that
G4
is an excellent candidate for additional development
toward anti-breast cancer clinical trials.
