192
N. N. Win and H. Morita
2.16 Diospyros burmanica Kurz.
Diospyros burmanica is a tree that belongs to the family Ebenaceae. It is widely
distributed in the Bago and Mandalay Regions of Myanmar and is locally known as
Hpun-mang, Mai-mak-ho-ling, Mai-mate-si or Te (Fig. 60) [334]. It is well known
as the plant of wild persimmon fruits, and there is no information on its traditional medicinal use. The chemical composition of D. burmanica were first reported
in 2012 [335]. The methanol extract of the wood of D. burmanica in Myanmar
exhibited potent activity against Leishmania major (MLC 6.25 μg/cm
3 ; MIC 1.25
μg/cm
3 ) in a previous screening [257]. Furthermore, three unprecedented bisnaphthoquinone analogs, burmanins A–C (292–294), five naphthols, 4,8-dimethoxy-3methyl-1-naphthol (295) [337], 2,8-dimethoxy-3-methyl-1-naphthol (296) [338],
8-methoxy-3-methyl-1-naphthol (297) [338], 5,8-dimethoxy-3-methyl-1-naphthol
(298) [339], and 4-hydroxy-5-methoxy-2-naphthalenecarboxaldehyde (299) [340],
and four naphthoquinones, 3-hydroxy-5-methoxy-2-methyl-1,4-naphthalenedione
(300) [336, 341], 5,8-dimethoxy-2-methyl-1,4-naphthalenedione (301) [342], 7hydroxy-8-methoxy-2-methyl-1,4-naphthalenedione (302) [343], and 5-methoxy-2methyl-1,4-naphthalenedione (303) [336, 344] were isolated from the CHCl 3 -soluble
fraction of the active methanol extract by a combination of various chromatographic
methods [335] (Fig. 61).
A leishmanicidal assay of 292–303 against the promastigote form of L. major
suggested that burmanin A (292) was the most active compound (IC 50 0.053 ± 2.7
× 10
−3
μM), followed by the dimeric analogs 293 (IC 50 0.18 ± 5.4 × 10
−3
μM) and
297 (IC 50 0.15 ± 11 × 10
−3
μM) and the monomeric naphthoquinone 303 (IC 50 3.3 ±
0.19 μM). In contrast, much weaker activity (> 38 μM) was observed from the other
monomeric naphthoquinone (302) and the naphthols (295–299). A cytotoxic assay of
292–303 against the murine macrophage-like cell line RAW264.7 also indicated that
burmanins A–C (292–294) showed weak toxicity (IC 50 values 24 ± 1.7, 31 ± 0.45,
and 22 ± 0.64 μM, respectively), which is required for potential antileishmanial
drug candidates in addition to high leishmanicidal activity, since the Leishmania
protozoan parasite dwells and multiplies within mammalian macrophages [336]. The
selectivity indexes of burmanins A–C (292–294) of 453, 172, and 147, respectively,
were relatively higher than those of reported natural monomeric naphthoquinones
determined from amastigotes of GFP-transfected L. major versus BMM (SI =
1.2–7.0) [345]. These results have suggested that burmanins A–C (292–294) could
be potential lead compounds for drugs in the treatment of parasitic diseases caused
by L. major.
2.17 Cinnamomum inunctum Kurz.
Cinnamomum inunctum belongs to the family Lauraceae. It is referred to as Kara-way
(Fig. 62) and distributed in the states of Kachin, Mon, and Shan of Myanmar [346],
N. N. Win and H. Morita
2.16 Diospyros burmanica Kurz.
Diospyros burmanica is a tree that belongs to the family Ebenaceae. It is widely
distributed in the Bago and Mandalay Regions of Myanmar and is locally known as
Hpun-mang, Mai-mak-ho-ling, Mai-mate-si or Te (Fig. 60) [334]. It is well known
as the plant of wild persimmon fruits, and there is no information on its traditional medicinal use. The chemical composition of D. burmanica were first reported
in 2012 [335]. The methanol extract of the wood of D. burmanica in Myanmar
exhibited potent activity against Leishmania major (MLC 6.25 μg/cm
3 ; MIC 1.25
μg/cm
3 ) in a previous screening [257]. Furthermore, three unprecedented bisnaphthoquinone analogs, burmanins A–C (292–294), five naphthols, 4,8-dimethoxy-3methyl-1-naphthol (295) [337], 2,8-dimethoxy-3-methyl-1-naphthol (296) [338],
8-methoxy-3-methyl-1-naphthol (297) [338], 5,8-dimethoxy-3-methyl-1-naphthol
(298) [339], and 4-hydroxy-5-methoxy-2-naphthalenecarboxaldehyde (299) [340],
and four naphthoquinones, 3-hydroxy-5-methoxy-2-methyl-1,4-naphthalenedione
(300) [336, 341], 5,8-dimethoxy-2-methyl-1,4-naphthalenedione (301) [342], 7hydroxy-8-methoxy-2-methyl-1,4-naphthalenedione (302) [343], and 5-methoxy-2methyl-1,4-naphthalenedione (303) [336, 344] were isolated from the CHCl 3 -soluble
fraction of the active methanol extract by a combination of various chromatographic
methods [335] (Fig. 61).
A leishmanicidal assay of 292–303 against the promastigote form of L. major
suggested that burmanin A (292) was the most active compound (IC 50 0.053 ± 2.7
× 10
−3
μM), followed by the dimeric analogs 293 (IC 50 0.18 ± 5.4 × 10
−3
μM) and
297 (IC 50 0.15 ± 11 × 10
−3
μM) and the monomeric naphthoquinone 303 (IC 50 3.3 ±
0.19 μM). In contrast, much weaker activity (> 38 μM) was observed from the other
monomeric naphthoquinone (302) and the naphthols (295–299). A cytotoxic assay of
292–303 against the murine macrophage-like cell line RAW264.7 also indicated that
burmanins A–C (292–294) showed weak toxicity (IC 50 values 24 ± 1.7, 31 ± 0.45,
and 22 ± 0.64 μM, respectively), which is required for potential antileishmanial
drug candidates in addition to high leishmanicidal activity, since the Leishmania
protozoan parasite dwells and multiplies within mammalian macrophages [336]. The
selectivity indexes of burmanins A–C (292–294) of 453, 172, and 147, respectively,
were relatively higher than those of reported natural monomeric naphthoquinones
determined from amastigotes of GFP-transfected L. major versus BMM (SI =
1.2–7.0) [345]. These results have suggested that burmanins A–C (292–294) could
be potential lead compounds for drugs in the treatment of parasitic diseases caused
by L. major.
2.17 Cinnamomum inunctum Kurz.
Cinnamomum inunctum belongs to the family Lauraceae. It is referred to as Kara-way
(Fig. 62) and distributed in the states of Kachin, Mon, and Shan of Myanmar [346],