178
N. N. Win and H. Morita
(223) [245, 246], mammea A/AC cyclo D (224) [245, 246], a mixture of theraphins B and C (205 and 206) [233], mammea B/AC cyclo F (225) [241, 243], and
deacetylmammea E/BA cyclo D (226) [247] (Fig. 45). Furthermore, the anti-austerity
assay used revealed that these isolated coumarins exhibited various potencies in a
concentration-dependent manner. The most potent activities at levels comparable
to that of the positive control, arctigenin (PC 100 of 1 μM) [225], were shown for
kayeassamins A (211), B (212), D (214), E (215), and G (217), each with a PC 100
value of 1 μM, which were followed by 216, 222 (2 μM) > 213 (4 μM) > 221 (8
μM) > 223 (16 μM) > 220, 226 (32 μM) > 218, 219, 205, 206, 225 (64 μM) > 224
(>256 μM). Total preferential cell death was observed within 12 h of treatment with
211, 212, and 214 and within 24 h of treatment with 215 and 217 at 1μM. These
results suggested that the presence of a geranyl moiety either at C-6 or C-8 in this
type of coumarin is important for enhancing the resultant anti-austerity activity of
this type of compound, which was in accordance with the observed preferential cytotoxicities in a concentration- as well as time-dependent manner for 211, 212, 214,
215 and 217. A further investigation has also revealed that kayeassamins A (211), B
(212), D (214), E (215), and G (217) trigger apoptosis-like morphological changes
in PANC-1 cells within 24 h at 4 μM, thereby causing the death of these cells. In
addition, a wound closure assay [248], which may be utilized to evaluate the effects
of compounds on the migratory ability of cancer cells, has also indicated not only the
preferential cytotoxicities of 211 and 212 in NDM but also the inhibitory activities
of 211 and 212 on PANC-1 cancer cell migration in a nutrient-rich medium. These
additional observations suggested that geranylated coumarins are potent preferential
cytotoxic agents as well as effective inhibitors against the migration of PANC-1 cells,
and so they might be useful to inhibit the metastatic process evident in pancreatic
cancer.
2.12 Cordia fragrantissima Kurz.
Cordia fragrantissima is a timber tree that belongs to the family Boraginaceae.
It occurs widely in Myanmar and is known locally as Sandawa or Taung-kalamet
(Fig. 46) [249]. A lotion manufactured by grinding the wood with water has been
applied to the hands and legs to relieve muscle pain. The bark is used to treat fever,
diarrhea, and skin diseases and as an anthelmintic. In turn, the fruits are employed as
a diuretic, expectorant, and anthelmintic and to treat lung and spleen diseases [250].
Although a number of phytochemicals such as quinones, flavonoids, and terpenoids
have been reported since 1990 from other Cordia species [251–256], the chemical
composition of C. fragrantissima was not reported until 2007.
In a screening procedure for antileishmanial activity against Leishmania major
by the heartwood constituents of C. fragrantissima, a methanol extract of the
wood collected in Myanmar exhibited in vitro antileishmanial activity (MLC
(minimum lethal concentration): 25 μg/cm
3 ; MIC (minimum inhibitory concentration): 12.5 μg/cm
3 ) [257]. Bioassay-guided fractionation of this active extract led to
the isolation of three new compounds, cordiaquinols I–K (227–229) [258], and five
N. N. Win and H. Morita
(223) [245, 246], mammea A/AC cyclo D (224) [245, 246], a mixture of theraphins B and C (205 and 206) [233], mammea B/AC cyclo F (225) [241, 243], and
deacetylmammea E/BA cyclo D (226) [247] (Fig. 45). Furthermore, the anti-austerity
assay used revealed that these isolated coumarins exhibited various potencies in a
concentration-dependent manner. The most potent activities at levels comparable
to that of the positive control, arctigenin (PC 100 of 1 μM) [225], were shown for
kayeassamins A (211), B (212), D (214), E (215), and G (217), each with a PC 100
value of 1 μM, which were followed by 216, 222 (2 μM) > 213 (4 μM) > 221 (8
μM) > 223 (16 μM) > 220, 226 (32 μM) > 218, 219, 205, 206, 225 (64 μM) > 224
(>256 μM). Total preferential cell death was observed within 12 h of treatment with
211, 212, and 214 and within 24 h of treatment with 215 and 217 at 1μM. These
results suggested that the presence of a geranyl moiety either at C-6 or C-8 in this
type of coumarin is important for enhancing the resultant anti-austerity activity of
this type of compound, which was in accordance with the observed preferential cytotoxicities in a concentration- as well as time-dependent manner for 211, 212, 214,
215 and 217. A further investigation has also revealed that kayeassamins A (211), B
(212), D (214), E (215), and G (217) trigger apoptosis-like morphological changes
in PANC-1 cells within 24 h at 4 μM, thereby causing the death of these cells. In
addition, a wound closure assay [248], which may be utilized to evaluate the effects
of compounds on the migratory ability of cancer cells, has also indicated not only the
preferential cytotoxicities of 211 and 212 in NDM but also the inhibitory activities
of 211 and 212 on PANC-1 cancer cell migration in a nutrient-rich medium. These
additional observations suggested that geranylated coumarins are potent preferential
cytotoxic agents as well as effective inhibitors against the migration of PANC-1 cells,
and so they might be useful to inhibit the metastatic process evident in pancreatic
cancer.
2.12 Cordia fragrantissima Kurz.
Cordia fragrantissima is a timber tree that belongs to the family Boraginaceae.
It occurs widely in Myanmar and is known locally as Sandawa or Taung-kalamet
(Fig. 46) [249]. A lotion manufactured by grinding the wood with water has been
applied to the hands and legs to relieve muscle pain. The bark is used to treat fever,
diarrhea, and skin diseases and as an anthelmintic. In turn, the fruits are employed as
a diuretic, expectorant, and anthelmintic and to treat lung and spleen diseases [250].
Although a number of phytochemicals such as quinones, flavonoids, and terpenoids
have been reported since 1990 from other Cordia species [251–256], the chemical
composition of C. fragrantissima was not reported until 2007.
In a screening procedure for antileishmanial activity against Leishmania major
by the heartwood constituents of C. fragrantissima, a methanol extract of the
wood collected in Myanmar exhibited in vitro antileishmanial activity (MLC
(minimum lethal concentration): 25 μg/cm
3 ; MIC (minimum inhibitory concentration): 12.5 μg/cm
3 ) [257]. Bioassay-guided fractionation of this active extract led to
the isolation of three new compounds, cordiaquinols I–K (227–229) [258], and five