植物来源抗疟倍半萜类天然产物研究(1972~2022)

doi:10.6023/cjoc202211029

摘要/Abstract

植物是筛选活性天然产物的重要来源, 1972年至2022年来从植物中分离得到了237个具有抗疟活性的倍半萜类化合物, 其类型主要包括链型倍半萜、吉玛烷型倍半萜、桉叶烷型倍半萜、乌药烷型倍半萜和愈创木烷型倍半萜等. 综述了植物来源的抗疟倍半萜类天然产物研究进展, 以期为后续研究开发新型抗疟药物提供参考.

关键词: 植物, 倍半萜, 倍半萜二聚体, 倍半萜三聚体, 天然产物, 抗疟活性

Plants are the important source for screening active natural products. A total of 237 sesquiterpenoids with antimalarial activity have been isolated from plants from 1972 to 2022, including chain-type, germacrane-type, eudesmane-type, lindenane-type, and guaiane-type. The research progress on antimalarial natural sesquiterpenoids from plants, which provide reference for further research and development of new antimalarial drugs, is summarized.

Key words: plants, sesquiterpenoids, sesquiterpenoid dimers, sesquiterpenoid trimers, natural products, antimalarial activity

引用此文

吴秀蓉, 肖朝江, 沈怡, 汤红霞, 朱俊逸, 姜北. 植物来源抗疟倍半萜类天然产物研究(1972~2022)[J]. 有机化学, 2023, 43(8): 2764-2789.

Xiurong Wu, Chaojiang Xiao, Yi Shen, Hongxia Tang, Junyi Zhu, Bei Jiang. Research Progress on Antimalarial Natural Sesquiterpenoids from Plants from 1972 to 2022[J]. Chinese Journal of Organic Chemistry, 2023, 43(8): 2764-2789.

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Compd.	Family	Plant	IC₅₀/(μmol•L^－1)	Year
Anthecotulide (1)	Asteraceae	Anthemis auriculata	16.11 (K1)	2008^[10]
4-Hydroxyanthecotulide (2)	Asteraceae	Anthemis auriculata	7.57 (K1)	2008^[10]
4-Acetoxyanthecotulide (3)	Asteraceae	Anthemis auriculata	16.65 (K1)	2008^[10]

Compd.	Family	Plant	IC₅₀/(μmol•L^－1)	Year
Anthecotulide (1)	Asteraceae	Anthemis auriculata	16.11 (K1)	2008^[10]
4-Hydroxyanthecotulide (2)	Asteraceae	Anthemis auriculata	7.57 (K1)	2008^[10]
4-Acetoxyanthecotulide (3)	Asteraceae	Anthemis auriculata	16.65 (K1)	2008^[10]

Compd.	Family	Plant			IC₅₀ or EC₅₀/(μmol•L^－1)	Year
Trichospirolide A (4)	Asteraceae	Trichospira verticillata			1.5 (Dd2)	2017^[11]
Trichospirolide B (5)	Asteraceae	Trichospira verticillata			37.0 (Dd2)	2017^[11]
9α-Acetoxy-15-hydroxy-8β-(2-methyl- butyryloxy)-14-oxo-4,5-trans-acantho- spermolide (6)	Asteraceae	Acanthospermum hispidum			2.23±0.09 (3D7)	2012^[12]
Urospermal A-15-O-acetate (7)	Asteraceae	Dicoma tomentosa			2.87±0.16 (3D7)	2012^[13]
					2.41±0.78 (W2)
Neurolenin A (8)	Asteraceae	Neurolaena lobata			0.92 (NF54)	1996^[14]
Neurolenin B (9)	Asteraceae	Neurolaena lobata			0.62 (NF54)	1996^[14]
Lobatin A (10)	Asteraceae	Neurolaena lobata			15.62 (NF54)	1996^[14]
Trichospirolide C (11)	Asteraceae	Trichospira verticillata			12.1 (Dd2)	2017^[11]
16,17-Dihydrobrachycalyxolide (12)	Asteraceae	Vernonia brachycalyx			8.3 (K39)	1998^[15]
					27 (3D7)
					5.9 (V1/S)
					32 (Dd2)
15-Acetoxy-8β-[(2-methylbutyryloxy)]- 14-oxo-4,5-cis-acanthospermolide (13)	Asteraceae		Acanthospermum hispidum	2.9±0.5 (3D7)			2012^[12]
Ineupatorolide A (14)	Asteraceae		Carpesium rosulatum	0.02 (D10)			2007^[16]
	Asteraceae		Carpesium rosulatum	86.5%, 10 mg•kg^－1•d^－1 (P. berghei)			2008^[17]
Schkuhrin I (15)	Asteraceae		Schkuhria pinnata	2.05 (NF54)			2013^[18]
Schkuhrin II (16)	Asteraceae		Schkuhria pinnata	1.67 (NF54)			2013^[18]
Lobatin B (17)	Asteraceae		Neurolaena lobata	16.51 (NF54)			1996^[14]
Trichospirolide D (18)	Asteraceae		Trichospira verticillata	44.3 (Dd2)			2017^[11]
8α-(2-Methylacryloyloxy)-3-oxo-1-de- soxy-1,2-dehydrohirsutinolide-13-O- acetate (19)	Asteraceae		Vernonia staehelinoides	0.67 (D10)			2007^[19]
				4.47 (K1)
8α-(5'-Acetoxysenecioyloxy)-3-oxo-1- desoxy-1,2-dehydrohirsutinolide-13-O- acetate (20)	Asteraceae		Vernonia staehelinoides	0.51 (D10)			2007^[19]
				5.48 (K1)
Vernolide D (21)	Asteraceae		Vernonia cinerea	3.5 (W2)			2006^[20]
8α-(4-Hydroxymethacryloyloxy)- hirsutinolide-13-O-acetate (22)	Asteraceae		Vernonia cinerea	3.7 (W2)			2006^[20]
8α-Tigloyloxy-hirsutinolide-13-O- acetate (23)	Asteraceae		Vernonia cinerea	3.9 (W2)			2006^[20]
5-O-Methyl-5-epiisogoyazensolide (24)	Asteraceae		Piptocoma antillana	6.2±0.5 (Dd2)			2014^[21]
15-O-Methylgoyazensolide (25)	Asteraceae		Piptocoma antillana	2.2±0.5 (Dd2)			2014^[21]
1-Oxo-3,10-epoxy-8-(2-methylacryloxy)- 15-acetoxygermacra-2,4,11(13)-trien- 6(12)-olide (26)	Asteraceae		Piptocoma antillana	8.0±0.4 (Dd2)			2014^[21]
5-epi-Isogoyazensolide (27)	Asteraceae		Piptocoma antillana	9.0±0.6 (Dd2)			2014^[21]
	Asteraceae		Camchaya calcarea	4.44 (K1)			2006^[22]
Goyazensolide (28)	Asteraceae		Camchaya calcarea	3.33 (K1)			2006^[22]
Lychnophorolide A (29)	Asteraceae		Camchaya calcarea	0.80 (K1)			2006^[22]
Lychnophorolide B (30)	Asteraceae		Camchaya calcarea	7.21 (K1)			2006^[22]
Isogoyazensolide (31)	Asteraceae		Camchaya calcarea	4.44 (K1)			2006^[22]
Isocentratherin (32)	Asteraceae		Camchaya calcarea	5.61 (K1)			2006^[22]
5-epi-Isocentratherin (33)	Asteraceae		Camchaya calcarea	8.01 (K1)			2006^[22]
9α-Hydroxy-8β-isovalerianyloxycaly- culatolide (34)	Asteraceae		Neurolaena lobata	19.27 (NF54)			1996^[14]
Vernolide (35)	Asteraceae		Vernonia colorata	5.16 (D10)			2009^[23]
	Asteraceae		Vernonia amygdalina	23.18 (K1)			2009^[24]
Hydroxyvernolide (36)	Asteraceae		Vernonia amygdalina	30.13 (K1)			2009^[24]
Parthenolide (37)	Magnoliaceae		Magnolia champaca	(85.18±0.50)%, 20 mg•kg^－1•d^－1 (P. berghei)			2017^[25]
Costunolide diepoxide (38)	Magnoliaceae		Magnolia champaca	(83.65±0.33)%, 20 mg•kg^－1•d^－1 (P. berghei)			2017^[25]
Peroxyferolide (39)	Magnoliaceae		Liriodendron tulipifera	18.3±0.3 (D10)			2011^[26]
				12.7±3.5 (Dd2)
Lipiferolide (40)	Magnoliaceae		Liriodendron tulipifera	5.9±2.3 (D10)			2011^[26]
				7.5±0.3 (Dd2)
Ridentin (41)	Asteraceae		Artemisia gorgonum	20.43±4.54 (FcB1)			2008^[27]
Hanphyllin (42)	Asteraceae		Artemisia gorgonum	9.26±3.62 (FcB1)			2008^[27]
Tagitinin C (43)	Asteraceae		Tithonia diversifolia	0.95 (FCA)			2003^[28], 2002^[29]
				0.72 (FCB1)
	Asteraceae		Tithonia diversifolia	1.55 (NF54)			2021^[30]
Orizabin (44)	Asteraceae		Tithonia diversifolia	2.28 (NF54)			2021^[30]
Vernopicrin (45)	Asteraceae		Vernonia guineensis	2.33±0.57 (Dd2)			2013^[31]
				1.77±0.32 (Hb3)
Vernangulide A (46)	Asteraceae		Distephanus angulifolius	1.90±0.10 (D10)			2009^[32]
				3.24±0.27 (W2)
1β-Hydroperoxyisonobilin (47)	Asteraceae		Anthemis nobilis	2.64 (FCH5)			1991^[33]
11(13)-Dehydroivaxillin (48)	Asteraceae		Carpesium cernum	87.7%, 10 mg•kg^－1•d^－1 (P. berghei)			2009^[34]
	Asteraceae		Carpesium cernum	2.01 (D10)			2009^[35]
Ivaxillin (49)	Asteraceae		Carpesium cernum	16.31 (D10)			2009^[35]
11-epi-Ivaxillin (50)	Asteraceae		Carpesium cernum	8.91 (D10)			2009^[35]
4,5α-Epoxy-6α-acetoxy-1(10)E,11(13)- germacradien-12,8α-olide (51)	Asteraceae		Oncosiphon piluliferum	1.63 (D10)			2007^[36]
Tatridin A (52)	Asteraceae		Oncosiphon piluliferum	1.51 (D10)			2007^[36]
Tanachin (53)	Asteraceae		Oncosiphon piluliferum	1.89 (D10)			2007^[36]
Furanodienone (54)	Burseraceae		Commiphora myrrh	7.4 (NF54)			2020^[37]
(1(10)E)-2-Methoxy-8,12-epoxygermacra- 1(10),7,11-trien-6-one (55)	Burseraceae		Commiphora myrrh	24 (NF54)			2020^[37]
2R-Methoxyfuranodiene (56)	Burseraceae		Commiphora myrrh	12 (NF54)			2020^[37]
1(10)Z,4Z-Furanodien-6-one (57)	Burseraceae		Commiphora myrrh	18 (NF54)			2020^[37]
Rel-2R-methyl-5S-acetoxy-4R-furanogerma- cr-1(10)Z-en-6-one (58)	Burseraceae		Commiphora myrrh	12 (NF54)			2020^[37]
(1R,2R,4S)-1,2-Epoxyfuranogermacr-10(15)- en-6-one (59)	Burseraceae		Commiphora myrrh	24 (NF54)			2020^[37]
5E,10(14)-Germacradien-1β,4β-diol (60)	Zingiberaceae		Reneilmia cincinnata	6.84 (D6)			1999^[38]
				133.83 (W2)
1(10)E,5E-Germacradien-4α-ol (61)	Zingiberaceae		Reneilmia cincinnata	6.93 (D6)			1999^[38]
				8.54 (W2)
6-O-Angeloyl-8-O-senecioyl-6β,8α,11- trihydroxygermacra-1(10)E,4E-diene (62)	Apiaceae		Daucus carota	96.4 (P. berghei)			2021^[39]
6-O-Tigloyl-8-O-isovaleryl-6β,8α,11- trihydroxygermacra-1(10)E,4E-diene (63)	Apiaceae		Daucus carota	1189 (P. berghei)			2021^[39]
6-O-Tigloyl-8-O-2-methylbutyryl-lα,6β,8α,11- tetrahydroxygermacra-4E,10(14)-diene (64)	Apiaceae		Daucus carota	115.8 (P. berghei)			2021^[39]
Daucovirgolide G (65)	Apiaceae		Daucus carota	17.5 (P. berghei)			2021^[39]

Compd.	Family	Plant			IC₅₀ or EC₅₀/(μmol•L^－1)	Year
Trichospirolide A (4)	Asteraceae	Trichospira verticillata			1.5 (Dd2)	2017^[11]
Trichospirolide B (5)	Asteraceae	Trichospira verticillata			37.0 (Dd2)	2017^[11]
9α-Acetoxy-15-hydroxy-8β-(2-methyl- butyryloxy)-14-oxo-4,5-trans-acantho- spermolide (6)	Asteraceae	Acanthospermum hispidum			2.23±0.09 (3D7)	2012^[12]
Urospermal A-15-O-acetate (7)	Asteraceae	Dicoma tomentosa			2.87±0.16 (3D7)	2012^[13]
					2.41±0.78 (W2)
Neurolenin A (8)	Asteraceae	Neurolaena lobata			0.92 (NF54)	1996^[14]
Neurolenin B (9)	Asteraceae	Neurolaena lobata			0.62 (NF54)	1996^[14]
Lobatin A (10)	Asteraceae	Neurolaena lobata			15.62 (NF54)	1996^[14]
Trichospirolide C (11)	Asteraceae	Trichospira verticillata			12.1 (Dd2)	2017^[11]
16,17-Dihydrobrachycalyxolide (12)	Asteraceae	Vernonia brachycalyx			8.3 (K39)	1998^[15]
					27 (3D7)
					5.9 (V1/S)
					32 (Dd2)
15-Acetoxy-8β-[(2-methylbutyryloxy)]- 14-oxo-4,5-cis-acanthospermolide (13)	Asteraceae		Acanthospermum hispidum	2.9±0.5 (3D7)			2012^[12]
Ineupatorolide A (14)	Asteraceae		Carpesium rosulatum	0.02 (D10)			2007^[16]
	Asteraceae		Carpesium rosulatum	86.5%, 10 mg•kg^－1•d^－1 (P. berghei)			2008^[17]
Schkuhrin I (15)	Asteraceae		Schkuhria pinnata	2.05 (NF54)			2013^[18]
Schkuhrin II (16)	Asteraceae		Schkuhria pinnata	1.67 (NF54)			2013^[18]
Lobatin B (17)	Asteraceae		Neurolaena lobata	16.51 (NF54)			1996^[14]
Trichospirolide D (18)	Asteraceae		Trichospira verticillata	44.3 (Dd2)			2017^[11]
8α-(2-Methylacryloyloxy)-3-oxo-1-de- soxy-1,2-dehydrohirsutinolide-13-O- acetate (19)	Asteraceae		Vernonia staehelinoides	0.67 (D10)			2007^[19]
				4.47 (K1)
8α-(5'-Acetoxysenecioyloxy)-3-oxo-1- desoxy-1,2-dehydrohirsutinolide-13-O- acetate (20)	Asteraceae		Vernonia staehelinoides	0.51 (D10)			2007^[19]
				5.48 (K1)
Vernolide D (21)	Asteraceae		Vernonia cinerea	3.5 (W2)			2006^[20]
8α-(4-Hydroxymethacryloyloxy)- hirsutinolide-13-O-acetate (22)	Asteraceae		Vernonia cinerea	3.7 (W2)			2006^[20]
8α-Tigloyloxy-hirsutinolide-13-O- acetate (23)	Asteraceae		Vernonia cinerea	3.9 (W2)			2006^[20]
5-O-Methyl-5-epiisogoyazensolide (24)	Asteraceae		Piptocoma antillana	6.2±0.5 (Dd2)			2014^[21]
15-O-Methylgoyazensolide (25)	Asteraceae		Piptocoma antillana	2.2±0.5 (Dd2)			2014^[21]
1-Oxo-3,10-epoxy-8-(2-methylacryloxy)- 15-acetoxygermacra-2,4,11(13)-trien- 6(12)-olide (26)	Asteraceae		Piptocoma antillana	8.0±0.4 (Dd2)			2014^[21]
5-epi-Isogoyazensolide (27)	Asteraceae		Piptocoma antillana	9.0±0.6 (Dd2)			2014^[21]
	Asteraceae		Camchaya calcarea	4.44 (K1)			2006^[22]
Goyazensolide (28)	Asteraceae		Camchaya calcarea	3.33 (K1)			2006^[22]
Lychnophorolide A (29)	Asteraceae		Camchaya calcarea	0.80 (K1)			2006^[22]
Lychnophorolide B (30)	Asteraceae		Camchaya calcarea	7.21 (K1)			2006^[22]
Isogoyazensolide (31)	Asteraceae		Camchaya calcarea	4.44 (K1)			2006^[22]
Isocentratherin (32)	Asteraceae		Camchaya calcarea	5.61 (K1)			2006^[22]
5-epi-Isocentratherin (33)	Asteraceae		Camchaya calcarea	8.01 (K1)			2006^[22]
9α-Hydroxy-8β-isovalerianyloxycaly- culatolide (34)	Asteraceae		Neurolaena lobata	19.27 (NF54)			1996^[14]
Vernolide (35)	Asteraceae		Vernonia colorata	5.16 (D10)			2009^[23]
	Asteraceae		Vernonia amygdalina	23.18 (K1)			2009^[24]
Hydroxyvernolide (36)	Asteraceae		Vernonia amygdalina	30.13 (K1)			2009^[24]
Parthenolide (37)	Magnoliaceae		Magnolia champaca	(85.18±0.50)%, 20 mg•kg^－1•d^－1 (P. berghei)			2017^[25]
Costunolide diepoxide (38)	Magnoliaceae		Magnolia champaca	(83.65±0.33)%, 20 mg•kg^－1•d^－1 (P. berghei)			2017^[25]
Peroxyferolide (39)	Magnoliaceae		Liriodendron tulipifera	18.3±0.3 (D10)			2011^[26]
				12.7±3.5 (Dd2)
Lipiferolide (40)	Magnoliaceae		Liriodendron tulipifera	5.9±2.3 (D10)			2011^[26]
				7.5±0.3 (Dd2)
Ridentin (41)	Asteraceae		Artemisia gorgonum	20.43±4.54 (FcB1)			2008^[27]
Hanphyllin (42)	Asteraceae		Artemisia gorgonum	9.26±3.62 (FcB1)			2008^[27]
Tagitinin C (43)	Asteraceae		Tithonia diversifolia	0.95 (FCA)			2003^[28], 2002^[29]
				0.72 (FCB1)
	Asteraceae		Tithonia diversifolia	1.55 (NF54)			2021^[30]
Orizabin (44)	Asteraceae		Tithonia diversifolia	2.28 (NF54)			2021^[30]
Vernopicrin (45)	Asteraceae		Vernonia guineensis	2.33±0.57 (Dd2)			2013^[31]
				1.77±0.32 (Hb3)
Vernangulide A (46)	Asteraceae		Distephanus angulifolius	1.90±0.10 (D10)			2009^[32]
				3.24±0.27 (W2)
1β-Hydroperoxyisonobilin (47)	Asteraceae		Anthemis nobilis	2.64 (FCH5)			1991^[33]
11(13)-Dehydroivaxillin (48)	Asteraceae		Carpesium cernum	87.7%, 10 mg•kg^－1•d^－1 (P. berghei)			2009^[34]
	Asteraceae		Carpesium cernum	2.01 (D10)			2009^[35]
Ivaxillin (49)	Asteraceae		Carpesium cernum	16.31 (D10)			2009^[35]
11-epi-Ivaxillin (50)	Asteraceae		Carpesium cernum	8.91 (D10)			2009^[35]
4,5α-Epoxy-6α-acetoxy-1(10)E,11(13)- germacradien-12,8α-olide (51)	Asteraceae		Oncosiphon piluliferum	1.63 (D10)			2007^[36]
Tatridin A (52)	Asteraceae		Oncosiphon piluliferum	1.51 (D10)			2007^[36]
Tanachin (53)	Asteraceae		Oncosiphon piluliferum	1.89 (D10)			2007^[36]
Furanodienone (54)	Burseraceae		Commiphora myrrh	7.4 (NF54)			2020^[37]
(1(10)E)-2-Methoxy-8,12-epoxygermacra- 1(10),7,11-trien-6-one (55)	Burseraceae		Commiphora myrrh	24 (NF54)			2020^[37]
2R-Methoxyfuranodiene (56)	Burseraceae		Commiphora myrrh	12 (NF54)			2020^[37]
1(10)Z,4Z-Furanodien-6-one (57)	Burseraceae		Commiphora myrrh	18 (NF54)			2020^[37]
Rel-2R-methyl-5S-acetoxy-4R-furanogerma- cr-1(10)Z-en-6-one (58)	Burseraceae		Commiphora myrrh	12 (NF54)			2020^[37]
(1R,2R,4S)-1,2-Epoxyfuranogermacr-10(15)- en-6-one (59)	Burseraceae		Commiphora myrrh	24 (NF54)			2020^[37]
5E,10(14)-Germacradien-1β,4β-diol (60)	Zingiberaceae		Reneilmia cincinnata	6.84 (D6)			1999^[38]
				133.83 (W2)
1(10)E,5E-Germacradien-4α-ol (61)	Zingiberaceae		Reneilmia cincinnata	6.93 (D6)			1999^[38]
				8.54 (W2)
6-O-Angeloyl-8-O-senecioyl-6β,8α,11- trihydroxygermacra-1(10)E,4E-diene (62)	Apiaceae		Daucus carota	96.4 (P. berghei)			2021^[39]
6-O-Tigloyl-8-O-isovaleryl-6β,8α,11- trihydroxygermacra-1(10)E,4E-diene (63)	Apiaceae		Daucus carota	1189 (P. berghei)			2021^[39]
6-O-Tigloyl-8-O-2-methylbutyryl-lα,6β,8α,11- tetrahydroxygermacra-4E,10(14)-diene (64)	Apiaceae		Daucus carota	115.8 (P. berghei)			2021^[39]
Daucovirgolide G (65)	Apiaceae		Daucus carota	17.5 (P. berghei)			2021^[39]

Compd.	Family	Plant	IC₅₀ or EC₅₀/(μmol•L^－1)	Year
Zingiberene-3,6-α-endoperoxide (66)	Asteraceae	Senecio selloi/Eupatorium rufescens	42.31 (FCH5)	1996^[40]
Zingiberene-3,6-β-endoperoxide (67)	Asteraceae	Senecio selloi/Eupatorium rufescens	42.31 (FCH5)	1996^[40]
Yingzhaosu A (68)	Annonaceae	Artabotrys uncinatus	0.12 (K1)	2005^[41]
69	Asteraceae	Artemisia persica	2.8±0.4 (K1)	2013^[42]
70	Asteraceae	Artemisia persica	14.9±1.7 (K1)	2013^[42]
71	Asteraceae	Artemisia persica	20.1±0.7 (K1)	2013^[42]
72	Asteraceae	Artemisia persica	19.1±2.2 (K1)	2013^[42]
1(S^*)-Hydroxy-α-bisabololoxide A acetate (73)	Asteraceae	Artemisia abrotanum	17.17 (K1)	1990^[43]