Synthesis and herbicidal activity evaluation of novel β-carboline derivatives

Article abstract of DOI:10.3390/molecules17043969

Based on the original structure of harmine, several novel 1,2,3,4-tetrahydro-β- carboline, β-carboline and 1-substituted-β- carboline derivatives bearing a substituted carbohydrazide group at C-3 were designed and synthesized to investigate the structureactivity relationship of their analogues. All of the compounds were characterized by infrared (IR), proton and carbon nuclear magnetic resonance (¹H-NMR, ¹³C-NMR), and mass spectroscopy (MS). The bioassay tests showed that N'-benzylidene-1-phenyl-β- carboline-3-carbohydrazide (C₂₅H ₁₈N₄O, m.w. 390.4) (c2) and N'-(4- trifluoromethylbenzylidene)- 1-phenyl-β-carboline-3-carbohydrazide (C26H17N4OF3, m.w. 458) (d2) exhibited good inhibitory activity against dicotyledonous and monocotyledonous weeds, with EC50 values of 4.83 μM and 14.25 μM, respectively.

Full text of DOI:10.3390/molecules17043969

Molecules 2012, 17, 3969-3980; doi:10.3390/molecules17043969
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Synthesis and Herbicidal Activity Evaluation of Novel
β-Carboline Derivatives
Qunfang Weng 1,2, Jingfei Huang 1,2, Yong Zeng 1,2, Yueye Deng 1,2 and Meiying Hu 1,2,
*
1
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education,Guangzhou 510642,
China; E-Mails: huabao@scau.edu.cn (Q.W.); huangjingfei1983@yahoo.com.cn (J.H.);
yongz800@163.com (Y.Z.); dengyueye@163.com (Y.D.)
2
Laboratory of Insect Toxicology, South China Agricultural University, Guangzhou 510642, China
* Author to whom correspondence should be addressed; E-Mail: humy@scau.edu.cn;
Tel.: +86-20-8528-0308; Fax: +86-20-8528-0292.
Received: 15 February 2012; in revised form: 15 March 2012 / Accepted: 22 March 2012 /
Published: 2 April 2012
Abstract: Based on the original structure of harmine, several novel 1,2,3,4-tetrahydro-β-
carboline, β-carboline and 1-substituted-β-carboline derivatives bearing a substituted
carbohydrazide group at C-3 were designed and synthesized to investigate the structure-
activity relationship of their analogues. All of the compounds were characterized by
infrared (IR), proton and carbon nuclear magnetic resonance (1H-NMR, 13C-NMR), and
mass spectroscopy (MS). The bioassay tests showed that N'-benzylidene-1-phenyl-β-
carboline-3-carbohydrazide (C25H18N4O, m.w. 390.4) (c2) and N'-(4-trifluoromethyl-
benzylidene)-1-phenyl-β-carboline-3-carbohydrazide (C26H17N4OF3, m.w. 458) (d2) exhibited
good inhibitory activity against dicotyledonous and monocotyledonous weeds, with EC50
values of 4.83 µM and 14.25 µM, respectively.
Keywords: N'-substituted-1,2,3,4-β-tetrahydro-β-carboline-3-carbohydrazide; β-carboline;
N'-substituted-β-carboline-3-carbohydrazides; 1-substituted-β-carboline-3-carbohydrazides;
herbicidal activity

Molecules 2012, 17
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1. Introduction
Harmine compounds and their structurally related compounds, belonging to the β-carboline
alkaloids class, are present in medicinal plants such as Peganum harmala and Eurycoma longifolia.
These compounds have recently drawn increasing interest due to their diverse biological activities,
including pharmacological, neurophysiologic and biochemical activities [1–6]. Some plants which
contain these compounds are used in traditional medicine in China, Brazil and other areas of the World
for their emmenagogue, abortifacient, anticancer, antispasmodic and sedative effects [7,8].
As for pest management, the extracts of Peganum L. plant species containing a mixture of harmine,
harmaline and norharman, as well as their derivatives, have long been proven to have insecticidal,
fungicidal and plant growth regulatory properties [9–14]. Some research has revealed that P. harmala
residues could cause great negative effects on seedling length, seedling dry weight, leaf area and
chlorophyll content of Avena fatua L. (Poaceae) and Convolvulus arvensis L. (Convolvulaceae),
showing their potential herbicidal activity [15,16], but there has been little systematic research on the
effect of substituents on the pesticidal activities, therefore, the present study was designed to
synthesize a series of novel β-carboline derivatives bearing a substituted carbohydrazide group at C-3,
followed by their in vivo herbicidal activity evaluation.
2. Results and Discussion
2.1. Chemistry
Previous structure-activity relationship studies had demonstrated the influence of substituents in
positions-1, -3, and -9 of the β-carboline skeleton for a variety of synthetic β-carboline derivatives [17–20].
In order to study the effect of main structure and the substituent groups at position-1 and -3 on their
herbicidal activity, we synthesized a series of 23 novel 1,2,3,4-tetrahydro-β-carboline and β-carboline
derivatives bearing a substituted carbohydrazide group at C-3 and substituted groups at C-1 according
to Love [17] (Scheme 1). According to their structural characteristics, these compounds could be
divided into four series, including four N'-substituted-1,2,3,4-tetrahydro-β-carboline-3-carbohydrazides,
12 N'-substituted-β-carboline-3-carbohydrazides, four N'-benzylidene-1-substituted-β-carboline-3-
carbohydrazides and three N'-substituted-benzylidene-1-substituted-β-carboline-3-carbohydrazides. All
1
13
these compounds were characterized by their melting point, mass, infrared, H-NMR and C-NMR
spectra that confirmed the proposed structures of the new compounds. It was also found that the
Pictet-Spengler reactions of L-tryptophan with different aldehydes were different, as the reaction rates
were not only related with the size of aldehydes, but also with the electronic properties of their substituents.
Thus, 1,2,3,4-tetrahydro-β-carboline could be produced by the reaction of paraformaldehyde with
L-tryptophan under anhydrous conditions. Benzaldehydes with an electron-withdrawing substituent
reacted more easily with L-tryptophan than those bearing an electron-donating substituent. In this
study, under the conditions of elevated temperature and increased pressure, condensation of
tetrahydro-β-carboline and β-carboline with aromatic aldehydes in the presence of dehydrating agents
under reflux in ethanol yielded the corresponding carbohydrazides. Because of the instability of
tetrahydro-β-carbolines, they were hard to react with aromatic aldehydes, especially those aldehydes
with electron-withdrawing substituents or high steric hindrance.

Molecules 2012, 17
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Scheme 1. The synthetic protocols for the target compounds.
COOCH3
COOH
R-CHO
COOH
CH OH
/ acid
reflux
SOCl2
3
/
NH
NH2
NH
N
H
N
H
N
H
cool
R
R
1a-1e
2a-2e
COOCH3
NH2NH2
CONHNH2
CONHN CH
R -CHO / acid
1
R1
NH
NH
NH
N
N
N
H
reflux
reflux
H
R
H
3a
a1-a4
2a-2e
KMnO4 /DMF
cool
CONHN
CH
COOCH3
CONHNH2
NH2NH2
R1
N
N
R1-CHO
N
/ acid
N
H
N
H
N
H
reflux
reflux
R
R
R
b1-b12, c1-c4, d1-d3
4b-4e
5b-5e
R = H, methyl, phenyl, 4-chlorobenzyl, 4-methoxyphenyl, 3,4,5-trimethoxyphenyl, 4-(trifluoro-
methyl)phenyl; R1 phenyl, 4-chlorobenzyl, 4-methoxyphenyl, 3,4,5-trimethoxyphenyl,
=
4-(trifluoromethyl)phenyl, 4-nitrophenyl, 2,4,6-trimethoxyphenyl, 2-hydroxybenzyl, 4-hydroxy-3-
methoxybenzyl, (5-chloro-3-methyl-1H-pyrazol-4-yl)methyl, diphenylmethyl, furan-2-ylmethyl.
2.2. Herbicidal Activity
The target compounds were screened for herbicidal activities against rape and barnyard grass. The
results (Table 1) indicated that these compounds showed some degree of herbicidal activities against
rape, but weak activity against barnyard grass.
Table 1. Herbicidal activity of compounds (% I; concentration, μg/mL).
B. campestris
E. crusgalli
Compound
100
10
100
10
a1
a2
a3
a4
b1
b2
b3
b4
b5
b6
b7
25.31
37.12
33.54
16.45
55.63
71.59
58.40
42.66
47.32
85.41
50.13
3.75
8.69
5.28
0.00
18.13
24.72
16.27
13.85
18.02
30.95
19.36
15.04
8.62
23.80
0.00
35.94
29.55
37.12
12.63
0.00
0.00
0.00
2.51
0.00
11.83
17.48
15.07
0.00
0.00
24.65
18.05
43.19
47.61

Molecules 2012, 17
3972
Table 1. Cont.
B. campestris
E. crusgalli
Compound
100
10
100
10
b8
b9
b10
b11
b12
c1
c2
c3
c4
d1
63.25
17.85
90.83
23.68
10.46
87.05
100
82.35
91.73
76.49
100
27.44
2.59
32.17
7.52
32.95
0.00
28.05
0.00
13.26
0.00
6.34
0.00
0.00
21.85
30.38
19.35
16.74
9.76
27.94
24.15
10.82
100
0.00
0.00
37.22
62.09
27.12
66.97
35.38
57.85
66.90
20.16
—
51.47
73.93
31.16
43.72
35.68
60.32
57.87
32.49
100
d2
d3
harmine
2,4-D
93.71
53.71
100
Their herbicidal activities were determined by the core structure and the substituents at positions
1 and 3. The fully aromatic β-carbolines showed better herbicidal activities than those with
tetrahydro-β-carboline moieties and the appropriate substituents at position 1 which could reinforce
their activities. In this research, it was found substituted phenyls with an electron-withdrawing
substituent and little steric hindrance had better activities. The substituents of position 3 could also
affect the activity. An electron-withdrawing substituent or substructure with a high herbicidal activity
could enhance their bioactivities. Furthermore, it was found that some seeds would not germinate after
treatment with compounds at the concentration of 100 μg/mL. On the other hand, the roots of the
control treated with 2,4-D (a common herbicide, Figure 1) were inhibited after germinating. According
to the primary screening results, two compounds—c2 and d2—with higher activity were selected for
further investigations of EC50 and probit (mortality%)-log (concentration) lines. The results are shown
in Table 2.
Figure 1. The structural formula of harmine and 2,4-D [(2,4-dichlorophenoxy)acetic acid].
Table 2. EC50 values of compounds c2 and d2.
Compound
y = a + bx
EC50
4.83
c2
d2
y = 4.4025 + 0.8710x
y = 2.5709 + 2.1052x
14.25

Molecules 2012, 17
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3. Experimental
3.1. General
All reagents were purchased from commercial suppliers and dried and purified when necessary.
Melting points were determined on an XT-4 binocular microscope (Beijing Tech Instrument Co.,
1
Beijing, China) and were uncorrected. H-NMR spectra were recorded in DMSO-d6 solutions with a
Bruker AC-P500 (500 MHz) instrument, using tetramethylsilane as an internal standard. Infrared
spectra were measured on an ACATAR 360 Fourier Transform Infrared Spectrometer using potassium
bromide (KBr) disks, scanning from 400 to 4,000 cm−1. MS were obtained on an Agilent 6890N-5975
instrument (Agilent Technologies, Inc., Palo Alto, CA, USA). Elemental analyses (C, H and N) were
carried out on an Elementar Vario EL CHNS Elemental Analyzer (Elementar, Hanau, Germany).
FAB-MS spectra were obtained from VG ZAB-HS spectrometer (VG Instrument Inc., Manchester,
UK). Silica gel F254 was used in analytical thin-layer chromatography (TLC) and silica gel was used
in column chromatography. Yields were not optimized.
3.1.1. General Synthesis
The synthetic route for the preparation of 1,2,3,4-tetrahydro-β-carboline-3-carbohydrazide 3a
and β-carboline-3-carbohydrazides 5a–e is presented in Scheme 1. Methyl tetrahydro-β-carboline-3-
carboxylates 2a–e were prepared through Pictet-Spengler condensation of L-tryptophan (1) with
polyoxymethylene (a), acetaldehyde (b), 3,4,5-trimethoxybenzaldehyde (c), 4-(trifluoromethyl)
benzaldehyde (d), and benzaldehyde (e), in acid media, and subsequent esterification of the
corresponding carboxylic acids with methanol and thionyl chloride. Oxidation of methyl
1,2,3,4-tetrahydro-β-carboline-3-carboxylates 2a–e with KMnO4 under cooled DMF, furnished methyl
β-carboline-3-carboxylates 4b–e. Conversion of 2a and 4b–e to 1,2,3,4-tetrahydro-β-carboline-3-
carbohydrazides 3a and β-carboline-3-carbohydrazides 5a–e was carried out by reaction with
hydrazine hydrate in ethanol under reflux according to the procedures described in literature for similar
compounds [21]. Condensation of 3a and 5b–e with the aromatic aldehydes 4-methoxybenzaldehyde,
4-nitrobenzaldehyde, 3,4,5-trimethoxybenzaldehyde, 2,4,6-trimethoxybenzaldehyde, 2-hydroxybenzaldehyde,
4-hydroxy-3-methoxybenzaldehyde, benzaldehyde, and 4-chlorobenzaldehyde under reflux in ethanol
yielded the carbohydrazides a1–4, b1–12, c1–4 and d1–3.
General Synthesis Procedure for N'-Substituted-1,2,3,4-tetrahydro-β-carboline-3-carbohydrazides
a1–4, N-Substituted-β-carboline-3-carbohydrazides b1–12, 1-Substituted-N-phenyl-β-carboline-3-
carbohydrazides c1–4 and 1-Substituted-N-substituted-β-carboline-3-carbohydrazides d1–3
A solution of 3a derivatives 5b–e (1 mmol) in ethanol (15 mL) was stirred and refluxed for 10 min
until complete dissolution. Then, a solution of aldehyde (1 mmol) in ethanol (3 mL) was added. Five
drops of acetic acid were added as a catalyst. The mixture was refluxed for 0.5 h–4 h. Precipitates were
filtered and dried, furnishing the title compounds a1–4 (b1–12, c1–4 and d1–3) in 62–90% yields.

Molecules 2012, 17
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3.1.2. Spectral Data
N'-Benzylidene-1,2,3,4-tetrahydro-β-carboline-3-carbohydrazide (C19H18N4O, m.w. 318.4) (a1). Yield:
1
83.5%; m.p.: 247–249 °C; FAB-MS m/z (M+1) 319; IR (cm−1): 3409, 2923, 1675, 1625; H-NMR:
2.81 (1H, q, J = 12.5 Hz, C(4)H, c), 3.12 (1H, dd, J = 18 Hz, C(4)H, c), 3.62 (1H, d, J = 13.5 Hz,
C(1)H, c), 3.68 (1H, dd, J = 14.5 Hz, N(2)H, c), 3.83 (1H, d, J = 14 Hz, C(1)H, c), 5.55 (1H, dd, J = 2 Hz,
13
C(3)H, c), 6.97 (9H, m, Ph), 8.98 (1H, s, NH), 10.77 (1H, s, N(9)H, c); C-NMR: 25.6, 32.1, 75.2,
103.5, 109.7, 117.3, 118.8, 120.5, 126.4, 127.9, 128.7, 130.2, 132.7, 133.7, 138.4, 147.2, 160.3; Anal.
Calcd for C19H18N4O: C, 71.68; H, 5.70; N, 17.60; Found: C, 71.35; H, 5.92; N, 17.53.
N'-(4-Methoxybenzylidene)-1,2,3,4-tetrahydro-β-carboline-3-carbohydrazide (C20H20N4O2, m.w. 348.4) (a2).
Yield: 93%; m.p.: 258–259 °C; FAB-MS m/z (M+1) 349; IR (cm−1): 3425, 2923, 2851, 1720, 1607,
1508, 1250, 1164, 1028; 1H-NMR: 2.77 (1H, q, J = 25 Hz, C(4)H, c), 3.10 (1H, dd, J = 18 Hz, C(4)H, c),
3.61 (2H, d, J = 14 Hz, C(1)H, c), 3.80 (1H, bs, N(2)H, c), 3.83 (3H, s, Ph-OCH3), 5.45 (1H, dd, J = 2 Hz,
C(3)H, c), 6.95–7.82(8H, m, Ph), 8.63(1 H, s, N=CH), 8.88 (1H, s, NH), 10.76 (1H, s, N(9)H, c);
13C-NMR: 25.8, 33.4, 55.6, 75.2, 103.5, 109.7, 115.2, 117.3, 118.8, 120.5, 126.4, 128.7, 130.2, 131.5,
133.7, 138.4, 160.1, 161.9; Anal. Calcd for C20H20N4O2: C, 68.95; H, 5.79; N, 16.08; Found: C, 68.71;
H, 5.84; N, 15.96.
N'-(3,4,5-Trimethoxybenzylidene)-1,2,3,4-tetrahydro-β-carboline-3-carbohydrazide (C22H24N4O4, m.w.
408.5) (a3). Yield: 87%; m.p.: 207–209 °C; FAB-MS m/z (M+1) 409; IR (cm−1): 3375, 2964, 2919,
1
1697, 1584, 1458, 1327, 1128; H-NMR: 2.80 (1H, q, J = 25 Hz, C(4)H, c), 3.12(1H, dd, J = 17.5 Hz,
C(4)H, c), 3.76 (9H, s, Ph-OCH3), 3.84 (1H, bs, N(2)H, c), 3.86 (2H, s, C(1)H, c), 5.45 (1H, dd, J = 1.5 Hz,
C(3)H, c), 6.89 (6H, m, Ph), 8.66 (1H, s, N=CH), 8.93 (1H, bs, NH), 10.78 (1H, s, N(9)H, c); 13C-NMR:
26.3, 32.9, 56.4, 62.5, 74.2, 106.7, 107.5, 112.8, 120.4, 120.9, 122.1, 127.3, 128.5, 135.6, 137.2, 141.9,
148.1, 160.5, 161.8; Anal. Calcd for C22H24N4O4: C, 64.69; H, 5.92; N, 13.72; Found: C, 64.57; H,
6.01; N, 13.65.
N'-(1,2,3,4-Tetrahydro-β-carboline-3-carbonyl)-N-(4-(trifluoromethyl)phenyl)formohydrazonamide
(C20H18F3N5O, 401.4) (a4). Yield: 62%; m.p.: 245–247 °C; FAB-MS m/z (M+1) 402; IR (KBr, cm−1):
1
3317, 2878, 1643, 1607, 1444, 1327, 1223, 1146; H-NMR: 2.66–2.68 (1H, q, J = 9.5 Hz, C(4)H, c),
2.78 (1H, dd, J = 18.5 Hz, C(4)H, c), 3.40 (1H, dd, J = 14 Hz, C(3)H, c), 3.86–3.90 (1H, d, J = 16 Hz,
C(1)H, c), 3.94 (1H, d, J = 16.5 Hz, C(1)H, c), 4.26 (2H, bs, N(2)H, NH), 6.91–7.35 (8H, m, Ph), 9.05
(1H, s, NH), 10.68 (H, s, N(9)H, c); 13C-NMR: 25.7, 32.1, 73.9, 104.2, 112.1, 116.4, 118.2, 120.3,
121.8, 124.5, 126.1, 126.9, 128.6, 130.5, 136.2, 146.3, 148.7, 158.2; Anal. Calcd for C20H18F3N5O: C,
59.85; H, 4.52; N, 17.45; Found: C, 59.74; H, 4.68; N, 17.31.
N'-Benzylidene-β-carboline-3-carbohydrazide (C19H14N4O, m.w. 314.3) (b1). Yield: 89%; m.p.:
1
289–291 °C; FAB-MS m/z (M+1) 315; IR (cm−1): 3293, 1658, 1620, 1524; H-NMR: 7.31 (1H, t,
J = 15 Hz, C(6)H, c), 7.45 (3H, m, J = 25.5 Hz, Ph(3,4,5)), 7.60 (1H, t, J = 15 Hz, C(7)H, c), 7.68 (1H,
d, J = 8 Hz, C(8)H, c), 7.74 (2H, d, J = 8 Hz, PH(2,6)), 8.45 (1H, d, J = 8 Hz, C(5)H, c), 8.67 (1H, s,
N=CH), 8.96 (1H, s, C(4)H, c), 8.98 (1H, s, C(1)H, c), 11.73–11.75 (1H, bs, –N(9)H, c), 12.07 (1H, s,
–NH–N); 13C-NMR: 108.3, 114.6, 118.2, 120.8, 121.8, 121.9, 127.5, 128.4, 130.3, 130.5, 133.1, 135.3,

Molecules 2012, 17
3975
138.2, 141.4, 148.5, 161.9; Anal. Calcd for C19H14N4O: C, 72.60; H, 4.49; N, 17.82; Found: C, 72.48;
H, 4.62; N, 17.69.
N'-(4-Methoxybenzylidene)-β-carboline-3-carbohydrazide (C20H16N4O2, m.w. 344.4) (b2). Yield: 84%;
m.p.: 273–275 °C; FAB-MS m/z (M+1) 345; IR (cm−1): 3447, 3409, 2925, 1658, 1604, 1251; 1H-NMR:
3.82 (3H, s, Ph(4)-OCH3), 7.03 (2H, d, J = 10.5 Hz, Ph(3,5)), 7.31–7.34 (1H, t, J = 14.5 Hz, C(6)H, c),
7.60 (1H, t, J = 16 Hz, C(7)H, c), 7.68 (3H, d, J = 8.5 Hz, C(8)H, c; Ph(2,6)), 8.44 (1H, d, J = 7.5 Hz,
C(5)H, c), 8.60 (1H, s, N=CH), 8.95 (1H, s, C(4)H, c), 8.96 (1H, s, C(1)H, c), 11.93 (1H, bs, –N(9)H, c),
13
12.01(1H, s, –NH–N); C-NMR: 55.8, 108.1, 113.5, 114.9, 118.4, 120.2, 121.7, 122.3, 127.6, 131.4,
133.8, 135.3, 138.1, 141.6, 149.2, 160.3, 160.9; Anal. Calcd for C20H16N4O2: C, 69.76; H, 4.68; N,
16.27; Found: C, 69.61; H, 4.86; N, 16.12.
N'-(3,4,5-Trimethoxybenzylidene)-β-carboline-3-carbohydrazide (C22H20N4O4, m.w. 404.4) (b3).
Yield: 83%; m.p.: 304–306 °C; FAB-MS m/z (M+1) 405; IR (cm−1): 3430, 3239, 2922, 1661, 1619,
1
1532; H-NMR: 3.72 (3H, s, Ph(4)-OCH3), 3.86 (6H, d, J = 4.5 Hz, Ph(3,5)-OCH3), 7.03 (2H, d,
J = 10.5 Hz, Ph(2,6)), 7.31 (1H, t, J = 15 Hz, C(6)H, c), 7.60 (1H, t, J = 15.5 Hz, C(7)H, c), 7.68 (1H,
d, J = 8 Hz, C(5)H, c), 8.45 (1H, d, J = 7.5 Hz, C(8)H, c), 8.55 (1H, s, C(4)H, c), 8.58 (1H, s, C(1)H,
c), 8.96 (1H, s, N=CH), 11.76 (1H, bs, –N(9)H, c), 12.03(1H, s, –NH–N); 13C-NMR: 56.5, 62.3, 107.2,
109.6, 114.4, 118.7, 120.4, 121.2, 121.9, 128.6, 130.1, 133.5, 134.8, 139.2, 141.6, 145.3, 148.9, 158.3,
161.7; Anal. Calcd for C22H20N4O4: C, 65.34; H, 4.98; N, 13.85; Found: C, 65.19; H, 5.24; N, 13.57.
N'-(2,4,6-Trimethoxybenzylidene)-β-carboline-3-carbohydrazide (C22H20N4O4, m.w. 404.4) (b4).
Yield: 54%; m.p.: 213–215 °C; FAB-MS m/z (M+1) 405; IR (cm−1): 3268, 2920, 2854, 1669, 1605,
1
1227; H-NMR: 3.82 (6H, s, Ph(2,6)-OCH3), 3.84 (3H, s, Ph(4)-OCH3), 6.30 (2H, s, Ph(3,5)), 7.30
(1H, t, J = 15 Hz, C(6)H, c), 7.59 (1H, t, J = 15.5 Hz, C(7)H, c), 7.67 (1H, d, J = 8 Hz, C(5)H, c), 8.43
(1H, d, J = 8 Hz, C(8)H, c), 8.63 (1H, s, C(4)H, c), 8.90 (1H, s, C(1)H, c), 8.93 (1H, s, N=CH), 11.69
13
(1H, bs, –N(9)H, c), 11.98(1H, s, –NH–N); C-NMR: 55.7, 55.9, 95.2, 105.4, 108.6, 112.5, 118.3,
120.7, 121.6, 123.1, 127.9, 134.5, 134.8, 139.5, 141.2, 145.3, 148.9, 160.1, 161.5; Anal. Calcd for
C22H20N4O4: C, 65.34; H, 4.98; N, 13.85; Found: C, 65.21; H, 5.19; N, 13.61.
N'-(4-Chlorobenzylidene)-β-carboline-3-carbohydrazide (C19H13ClN4O, m.w. 348.8) (b5). Yield: 93%;
m.p.: 269–271 °C; FAB-MS m/z (M+1) 349; IR (cm−1): 3272, 1679, 1626, 1494; 1H-NMR: 7.31 (1H, t,
J = 15 Hz, C(6)H, c), 7.53 (2H, d, J = 8.5 Hz, Ph(3,5)), 7.60 (1H, t, J = 16 Hz, C(7)H, c), 7.68 (1H, d,
J = 8 Hz, C(5)H, c), 7.75 (2H, d, J = 8.5 Hz, Ph(2,6)), 8.45 (1H, d, J = 8 Hz, C(8)H, c), 8.67 (1H, s,
C(4)H, c), 8.96 (1H, s, C(1)H, c), 8.98 (1H, s, N=CH), 11.762 (1H, bs, –N(9)H, c), 12.03(1H, s, –NH–N);
13C-NMR: 109.2, 113.8, 118.6, 121.1, 121.9, 123.1, 127.9, 130.4, 131.7, 134.1, 134.6, 137.8, 138.3,
139.5, 145.3, 148.9, 160.1; Anal. Calcd for C19H13ClN4O: C, 65.43; H, 3.76; N, 16.06; Found: C,
65.28; H, 3.95; N, 15.87.
N'-(4-Nitrobenzylidene)-β-carboline-3-carbohydrazide (C19H13N5O3, m.w. 359.3) (b6). Yield: 92%;
1
m.p.: >300 °C; FAB-MS m/z (M+1) 360; IR (cm−1): 3446, 3230, 1684, 1627, 1518; H-NMR: 7.32
(1H, t, J = 15.5 Hz, C(6)H, c), 7.61 (1H, t, J = 15 Hz, C(7)H, c), 7.68 (1H, d, J = 8.5 Hz, C(5)H, c),
7.99 (2H, d, J = 8.5 Hz, Ph(2,6)), 8.32 (2H, d, J = 9 Hz, Ph(3,5)), 8.46 (1H, d, J = 8 Hz, C(8)H, c),

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8.79 (1H, s, C(4)H, c), 8.97 (1H, s, C(1)H, c), 9.00 (1H, s, N=CH), 12.04 (1H, bs, –N(9)H, c), 12.40
(1H, s, –NH–N); 13C-NMR: 108.7, 114.1, 119.2, 120.6, 121.3, 123.7, 128.2, 134.2, 134.7, 134.6,
137.8, 139.5, 141.7, 145.4, 147.6, 158.3, 161.2; Anal. Calcd for C19H13N5O3: C, 63.51; H, 3.65; N,
19.49; Found: C, 63.36; H, 3.83; N, 19.21.
N'-(2-Hydroxybenzylidene)-β-carboline-3-carbohydrazide (C19H14N4O2, m.w. 330.3) (b7). Yield: 83%;
m.p.: 283–285 °C; FAB-MS m/z (M+1) 331; IR (cm−1): 3457, 3254, 1663, 1620, 1493, 1351; 1H-NMR:
6.93 (2H, q, J = 10.5 Hz, Ph(3,5)), 7.30 (2H, m, J = 23.5 Hz, C(6)H, c; Ph(4)), 7.46 (1H, d, J = 7.5 Hz,
C(5)H, c), 7.59 (1H, m, J = 32 Hz, Ph(6)), 7.69 (1H, t, J = 8.5 Hz, C(7)H, c), 8.44 (1H, d, J = 7.5 Hz,
C(8)H, c), 8.85 (1H, s, C(4)H, c), 8.97 (1H, s, C(1)H, c), 8.98 (1H, s, N=CH), 11.62 (1H, bs, –N(9)H, c),
12.05(1H, s, –NH–N), 12.45 (1H, s, Ph-OH); 13C-NMR: 108.6, 114.3, 118.9, 120.1, 120.4, 120.9,
121.5, 123.8, 125.3, 127.6, 134.2, 135.1, 135.7, 138.3, 139.6, 145.2, 147.8, 160.3, 160.7; Anal. Calcd
for C19H14N4O2: C, 69.08; H, 4.27; N, 16.96; Found: C, 68.94; H, 4.58; N, 16.72.
N'-(4-Hydroxy-3-methoxybenzylidene)-β-carboline-3-carbohydrazide (C20H16N4O3, m.w. 360.4) (b8).
Yield: 83%; m.p.: 163–165 °C; FAB-MS m/z (M+1) 361; IR (cm−1): 3430, 2924, 1663, 1600, 1505,
1380, 1278; 1H-NMR: 3.85 (3H, s, Ph(4)-OCH3), 6.85 (1H, d, J = 8 Hz, Ph(5)), 7.08 (1H, t, J = 16.5 Hz,
C(6)H, c), 7.31 (2H, m, J = 18 Hz, Ph(2,6)), 7.60 (1H, d, J = 23.5 Hz, C(5)H, c), 7.67 (1H, t, J = 8 Hz,
C(7)H, c), 8.44 (1H, d, J = 7.5 Hz, C(8)H, c), 8.54 (1H, s, C(4)H, c), 8.94 (1H, s, C(1)H, c), 8.95 (1H,
13
s, N=CH), 9.54 (1H, bs, Ph-OH), 11.74 (1H, bs, –N(9)H, c), 12.01 (1H, s, –NH–N); C-NMR: 56.4,
109.2, 114.1, 114.8, 119.2, 119.9, 120.6, 122.1, 123.5, 126.7, 128.3, 131.9, 135.4, 138.3, 139.6, 145.2,
147.6, 148.1, 150.8, 160.3; Anal. Calcd for C20H16N4O3: C, 66.66; H, 4.48; N, 15.55; Found: C, 66.38;
H, 4.65; N, 15.29.
N'-(Furan-2-ylmethylene)-β-carboline-3-carbohydrazide (C17H12N4O2, m.w. 304.3) (b9). Yield: 61%;
m.p.: >300 °C; FAB-MS m/z (M+1) 305; IR (cm−1): 3284, 1658, 1622; 1H-NMR: 6.64 (1H, t, J = 3 Hz,
furan(4)), 6.90 (1H, d, J = 3.5 Hz, furan(3)), 7.30 (1H, t, J = 15 Hz, C(6)H, c), 7.61 (1H, d, J = 8 Hz,
furan(5)), 7.67 (1H, t, J = 8 Hz, C(7)H, c), 7.86 (1H, s, C(4)H, c), 8.44 (1H, d, J = 8 Hz, C(8)H, c),
8.58 (1H, s, C(1)H, c), 8.95 (1H, d, J = 5 Hz, C(5)H, c), 8.97 (1H, s, N=CH), 11.74 (1H, d, J = 15 Hz,
13
–N(9)H, c), 12.02 (1H, s, -NH–N); C-NMR: 108.7, 114.5, 115.8, 118.4, 119.3, 120.6, 122.1, 123.5,
128.3, 135.4, 137.6, 138.6, 139.6, 145.5, 148.3, 150.8, 160.4; Anal. Calcd for C17H12N4O2: C, 67.10;
H, 3.97; N, 18.41; Found: C, 66.85; H, 4.18; N, 18.27.
N'-((5-Chloro-3-methyl-1H-pyrazol-4-yl)methylene)-β-carboline-3-carbohydrazide (C17H13ClN6O, m.w.
352.8) (b10). Yield: 74%; m.p.: 259–261 °C; FAB-MS m/z (M+1) 353; IR (cm−1): 3430, 3239, 2922,
1661, 1619, 1532; 1H-NMR: 2.50 (3H, s, pyrazole-CH3), 7.31 (1H, q, J = 15 Hz, C(6)H, c), 7.60 (1H,
dd, J = 19.5 Hz, C(7)H, c), 7.67 (1H, d, J = 8 Hz, C(5)H, c), 8.43 (1H, d, J = 7.5 Hz, C(8)H, c), 8.57
(1H, s, N=CH), 8.91 (1H, s, C(4)H, c), 8.94 (1H, s, C(1)H, c), 11.69–11.71 (1H, bs, –N(9)H, c), 11.96
(1H, s, –NH–N), 13.18 (1H, bs, NH, pyrazole); 13C-NMR: 15.7, 107.2, 112.1, 112.8, 117.5, 119.6,
120.1, 124.7, 128.3, 134.6, 138.3, 138.6, 144.2, 145.6, 148.3, 149.8, 161.2; Anal. Calcd for
C17H13ClN6O: C, 57.88; H, 3.71; N, 23.82; Found: C, 57.63; H, 3.96; N, 23.68.

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N'-(β-Carboline-3-carbonyl)-N-(4-(trifluoromethyl)phenyl)formohydrazonamide (C20H13F3N4O, m.w.
382.3) (b11). Yield: 85%; m.p.: 248–250 °C; FAB-MS m/z (M+1) 398; IR (cm−1): 3248, 3222, 1647,
1
1617, 1337; H-NMR: 4.58 (1H, bs, N=C–NH), 6.92–7.02 (2H, m, Ph(2,6)), 7.20 (1H, q, J = 10 Hz,
C(6)H, c), 7.30 (1H, d, J = 8 Hz, C(5)H, c), 7.39 (1H, dd, J = 10 Hz, C(7)H, c), 7.56 (3H, m, N=CH;
Ph(3,5)), 8.38 (1H, d, J = 15 Hz, C(8)H, c), 8.81 (1H, s, C(4)H, c), 8.88 (1H, s, C(1)H, c), 11.64 (1H,
bs, –N(9)H, c), 11.97 (1H, s, -NH–N); 13C-NMR: 109.6, 112.8, 117.5, 118.3, 119.6, 121.5, 124.5,
128.4, 128.9, 130.2, 131.8, 134.4, 134.8, 144.2, 147.6, 148.2, 150.3, 160.7; Anal. Calcd for
C20H13F3N4O: C, 60.45; H, 3.55; N, 17.62; Found: C, 60.27; H, 3.74; N, 17.39.
N'-(Diphenylmethylene)-β-carboline-3-carbohydrazide (C25H18N4O, m.w. 390.4) (b12). Yield: 70%;
1
m.p.: >300 °C; FAB-MS m/z (M+1) 391; IR (cm−1): 3257, 3175, 1667, 1624, 1495, 1254; H-NMR:
7.31 (1H, t, J = 10 Hz, C(6)H, c), 7.43 (5H, m, Ph1(2,3,4,5,6)), 7.60 (5H, m, Ph2(2,3,4,5,6)), 7.64 (1H,
d, J = 8.5 Hz, C(5)H, c), 7.71 (1H, t, J = 10.5 Hz, C(7)H, c), 8.43 (1H, d, J = 7.5 Hz, C(8)H, c), 8.64
(1H, s, C(4)H, c), 8.96 (1H, s, C(1)H, c), 11.03 (1H, bs, –N(9)H, c), 12.04(1H, s, –NH–N); 13C-NMR:
108.4, 115.7, 118.1, 120.6, 121.4, 124.7, 128.3, 128.8, 131.2, 133.7, 134.1, 134.9, 138.3, 145.6, 148.6,
160.2, 160.8; Anal. Calcd for C25H18N4O: C, 76.91; H, 4.65; N, 14.35; Found: C, 76.68; H, 4.82;
N, 14.16.
N'-Benzylidene-1-methyl-β-carboline-3-carbohydrazide (C20H16N4O, m.w. 328.4) (c1). Yield: 63%;
m.p.: >300 °C; FAB-MS m/z (M+1) 329; IR (cm−1): 3275, 2921, 1667, 1623, 1523; 1H-NMR: 2.91 (3H, s,
–CH3), 7.30 (1H, m, J = 16.2 Hz, C(6)H, c), 7.45 (1H, m, J = 8.4 Hz, C(7)H, c), 7.48 (2H, m, J = 14.4 Hz,
C(3,5)H, Ph), 7.59 (1H, m, J = 16.2 Hz, C(4)H, Ph), 7.66 (1H, m, J = 8.4 Hz, C(8)H, c), 7.76 (2H, d,
J = 8.4 Hz, C(2,6)H, Ph), 8.40 (1H, d, J = 7.8 Hz, C(5)H, c), 8.68 (1H, s, C(4)H, c), 8.80 (1H, s, –N=CH),
11.83 (1H, s, –NH, c), 12.03 (1H, s, –NH–N); 13C-NMR: 14.8, 111.5, 114.7, 119.6, 120.1, 124.7, 125.3,
128.8, 129.7, 134.2, 138.5, 139.6, 144.2, 145.6, 147.3, 148.7, 150.3, 159.8; Anal. Calcd for
C20H16N4O: C, 73.15; H, 4.91; N, 17.06; Found: C, 72.98; H, 5.06; N, 16.85.
N'-Benzylidene-1-phenyl-β-carboline-3-carbohydrazide (C25H18N4O, m.w. 390.4) (c2). Yield: 87%;
1
m.p.: 271–273 °C; FAB-MS m/z (M+1) 391; IR (cm−1): 3281, 3200, 1667, 1624, 1518; H-NMR: 7.37
(1H, m, J = 15.6 Hz, C(6)H, c), 7.46 (1H, m, J = 15.6 Hz, C(4)H, Ph1), 7.48 (2H, m, J = 15.6 Hz,
C(3,5)H, Ph1), 7.60 (1H, m, J = 10.2 Hz, C(7)H, c), 7.62 (1H, m, J = 10.2 Hz, C(8)H, c), 7.70 (3H, m,
J = 28.2 Hz, C(3,4,5)H, Ph2), 7.78 (2H, t, J = 8.4 Hz, C(2,6)H, Ph1), 8.22 (2H, m, J = 8.4 Hz, C(2,6)H,
Ph2), 8.48 (1H, d, J = 7.8 Hz, C(4)H, c), 8.68 (1H, s, C(5)H, c), 8.97 (1H, s, –N = CH), 11.81 (1H, s,
–NH, c), 11.93 (1H, s, –NH–N); 13C-NMR: 111.3, 116.1, 119.7, 121.4, 123.9, 126.5, 128.7, 128.9,
129.2, 129.5, 130.2, 130.8, 131.6, 132.1, 134.8, 136.5, 139.2, 142.7, 143.2, 149.3, 161.8; Anal. Calcd
for C25H18N4O: C, 76.91; H, 4.65; N, 14.35; Found: C, 76.72; H, 4.84; N, 14.19.
N'-Benzylidene-1-(4-(trifluoromethyl)phenyl)-β-carboline-3-carbohydrazide (C26H17F3N4O, m.w. 458.4)
(c3). Yield: 80.5%; m.p.: 235–237 °C; FAB-MS m/z (M+1) 459; IR (cm−1): 3436, 1730, 1622, 1325;
1H-NMR: 7.35–8.43 (13H, Ph1, Ph2, c), 8.67 (1H, s, C(4)H, c), 9.02 (1H, s, –N=CH), 11.87 (1H, s,
–NH, c), 12.07 (1H, s, –NH–N); 13C-NMR: 112.5, 115.7, 120.1, 121.3, 122.9, 124.3, 127.3, 128.8,
129.1, 130.5, 131.2, 131.8, 134.7, 135.6, 138.5, 139.6, 141.6, 144.2, 147.3, 148.7, 160.8; Anal. Calcd
for C26H17F3N4O: C, 68.12; H, 3.74; N, 12.22; Found: C, 67.94; H, 3.97; N, 12.08.

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N'-Benzylidene-1-(4-chlorophenyl)-β-carboline-3-carbohydrazide (C25H17ClN4O, m.w. 424.9) (c4).
Yield: 86%; m.p.: 220–221 °C; FAB-MS m/z (M+1) 425; IR (cm−1): 3419, 1683, 1624, 1511, 1351;
1H-NMR: 7.34 (1H, q, J = 15.6 Hz, C(6)H, c), 7.46 (3H, m, J = 30.6 Hz, C(3,4,5)H, Ph2), 7.62 (1H, m,
J = 16.2 Hz, C(7)H, c), 7.70 (1H, d, J = 8.4 Hz, C(8)H, c), 7.73 (2H, d, J = 15.6 Hz, C(3,5)H, Ph1),
7.77 (2H, m, J = 8.4 Hz, C(2,6)H，Ph2), 8.26 (2H, d, J = 9 Hz, C(2,6)H, Ph1), 8.48 (1H, d, J = 8.4 Hz,
C(5)H, c), 8.68 (1H, s, C(4)H, c), 8.98 (1H, s, –N=CH), 11.83 (1H, s, –NH, c), 11.97 (1H, s, –NH–N);
13C-NMR: 112.7, 114.9, 120.3, 121.6, 122.9, 124.3, 128.1, 129.4, 130.5, 131.7, 132.8, 134.2, 135.6,
138.5, 139.6, 141.6, 144.8, 148.1, 148.5, 160.3; Anal. Calcd for C25H17ClN4O: C, 70.67; H, 4.03; N,
13.19; Found: C, 70.42; H, 4.29; N, 13.05.
N'-(4-Trifluoromethylbenzylidene)-1-(4-trifluoromethyl-phenyl)-β-carboline-3-carbohydrazide) (C27H16F6N4O,
m.w. 526.4) (d1). Yield: 83.9%, m.p.: 289–290 °C; FAB-MS m/z (M+1) 527; IR (cm−1): 3438, 1735,
1
1658, 1381; H-NMR: 7.34–8.48 (12H, Ph1, Ph2, c), 8.75 (1H, s, C(4)H, c), 8.99 (1H, s, –N=CH),
12.02 (1H, s, –NH, c), 12.09 (1H, s, –NH–N); 13C-NMR: 112.7, 114.7, 120.3, 121.5, 122.9, 124.3,
127.3, 128.8, 129.1, 131.2, 132.7, 138.5, 144.6, 147.3, 148.5, 149.2, 150.9, 161.8; Anal. Calcd for
C27H16F6N4O: C, 61.60; H, 3.06; N, 10.64; Found: C, 61.38; H, 3.24; N, 10.47.
N'-(4-Trifluoromethylbenzylidene)-1-phenyl-β-carboline-3-carbohydrazide (C26H17N4OF3, m.w. 458.4)
(d2). Yield: 86.6%, m.p.: 235–237 °C; FAB-MS m/z (M+1) 459; IR (cm−1): 3379, 1723, 1594, 1487,
1364; 1H-NMR: 7.33–8.76 (13H, Ph1, Ph2, c), 8.98 (1H, s, C(4)H, c), 9.00 (1H, s, –N=CH), 11.98 (1H,
13
s, –NH, c), 11.99 (1H, s, –NH–N); C-NMR: 112.5, 114.9, 120.4, 121.8, 122.5, 125.2, 127.3, 128.1,
129.3, 130.5, 131.2, 131.8, 134.7, 135.6, 138.5, 139.6, 142.6, 145.2, 148.3, 148.5, 160.2; Anal. Calcd
for C26H17F3N4O: C, 68.12; H, 3.74; N, 12.22; Found: C, 67.96; H, 3.97; N, 12.11.
N'-(4-Trifluoromethylbenzylidene)-1-(4-chlorophenyl)-β-carboline-3-carbohydrazide (C26H16ClN4OF3,
m.w. 492.9) (d3). Yield: 88.8%, m.p.: 140–142 °C; FAB-MS m/z (M+1) 493; IR (cm−1): 3427, 1692,
1
1583, 1491; H-NMR: 7.36–8.76 (12H, Ph1, Ph2, c), 8.76 (1H, s, C(4)H, c), 8.99 (1H, s, –N=CH),
12.02 (1H, s, –NH, c), 12.03 (1H, s, –NH–N); 13C-NMR: 112.7, 115.1, 120.6, 121.5, 121.9, 124.7,
127.2, 128.4, 129.5, 132.2, 132.7, 138.5, 144.6, 147.3, 148.2, 148.9, 150.4, 160.6; Anal. Calcd for
C26H16ClF3N4O: C, 63.36; H, 3.27; N, 11.37; Found: C, 63.19; H, 3.45; N, 11.24.
3.2. Biological Assays
All compounds were formulated as 10 g/L emulsified concentrates using DMSO as solvent and
TW-80 as emulsification reagent. The stock solutions were diluted with water to the required
concentration and applied to pot-grown plants in a greenhouse at 23 ± 1 °C, 60 ± 5% relative humidity
(RH), 10 flux light intensity and 8 h/day photoperiod. Twenty seeds of each weed species including
Chinese cabbage (rape, Brassica campestris L. ssp.) and barnyard grass (Echinochloa crusgalli) were
chosen for testing. Seedlings were grown in the test plate of 9-cm diameter containing two pieces of
filter paper and 9 mL solution of the tested compound (100 mg/L and 10 mg/L, respectively). Distilled
water and 2,4-D were used as the comparison compounds. The herbicidal activity was assessed by the
inhibitory rate in comparison with the distilled water. The heights of the above-ground parts of the
seedlings, their root lengths and fresh weights in each cup were measured, and the means were

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calculated. The percentage inhibition was used to describe the control efficiency of the compounds.
Range from 0 to 100%, 0% means no effect and 100% means inhibition. The test was repeated three
times; means were calculated and shown as activity in Table 1. The compounds with higher activity
were selected for further investigations of EC50 and probit (mortality%)-log (concentration) lines,
which are shown in Table 2.
4. Conclusions
New 1,2,3,4-tetrahydro-β-carboline, β-carboline and 1-substituted-β-carboline derivatives bearing a
substituted carbohydrazide group at C-3 were designed and synthesized to study the structure-activity
relationships of their analogues. The results showed that some of the newly synthesized carbohydrazide
derivatives carrying phenyl groups substituted with an electron-withdrawing substituent could be used
for the further development of novel herbicides.
Acknowledgments
The present study was supported by grants from the China National Nature Science Foundation
(31171870) and China National Nature Science Foundation (31171882).
References and Notes
1. Carbrera, G.M.; Seldes, A.M. A β-carboline alkaloid from the soft coral lignopsis spongiosum.
J. Nat. Prod. 1999, 62, 759–760.
2. Glennon, R.A.; Dukat, M.; Brella, B.; Hong, S.S.; Constantino, L.; Teitler, M.; Smith, C.; Egan, C.;
Davis, K.; Mattson, M.V. Binding of β-carbolines and related agents at serotonin (5-HT2 and
5-HT1A), dopamine (D2) and benzodiazepines receptors. Drug Alcohol Depend. 2000, 60, 121–132.
3. Kotanen, S.; Huybrechts, J.; Cerstiaens, A.; Zoltan, K.; Daloze, D.; Baggerman, G.; Forgo, P.;
Loof, A.D.; Schoofs, L. Identification of tryptophan and beta-carboline as paralysins in larvae of
the yellow mealworm, Tenebrio molitor. Biochem. Biophys. Res. Commun. 2003, 310, 64–71.
4. Song, X.H.; Liu, X.H.; Lin, Y.C. Metabolites of mangrove fungus NO.K23 and interaction of
carboline with DNA (in Chinese). Chin. J. Trop. Oceanogr. 2004, 23, 66–70.
5. Herraiz, T.; Chaparro, C. Analysis of monoamine oxidase enzymatic activity by reversed-phase
high performance liquid chromatography and inhibition by β-carboline alkaloids occurring in
foods and plants. J. Chromatogr. A 2006, 1120, 237–243.
6. Herraiz, T.; Chaparro, C. Human monoamine oxidase enzyme inhibition by coffee and
β-carbolines norharman and harman isolated from coffee. Life Sci. 2006, 78, 795–802.
7. Sun, D.J.; Lee, Y. Advance in Peganum multisectum and main active component of norharman
(in Chinese). J. Xinjiang Med. Univ. 2003, 26, 125–128.
8. Cao, R.H.; Peng, W.L.; Wang, Z.H.; Xu, A.L. β-Carboline alkaloids: Biochemical and
pharmacological functions. Curr. Med. Chem. 2007, 14, 479–500.
9. Liu, J.X.; Zhao, G.L. Effects of substance extracted from Peganum Multisectum Maxim Bobr on
growth of maize (in Chinese). Acta Bot. Boreal.-Occident. Sin. 2004, 23, 2200–2203.

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10. Yao, W.Q.; Wang, J.R.; Zhang, P.Z.; Peng, J.Y.; Zhang, Y.Y. Insecticidal activity of alcohol
extracts from Peganum harmala (in Chinese). Acta Bot. Boreal.-Occident. Sin. 2004, 24, 1096–1099.
11. Weng, Q.F.; Zhong, G.H.; Hu, M.Y.; Luo, J.J. Bioactivities and physiological effects of extracts
of Peganum harmala against Bursaphelenchus xylophilus (in Chinese). Sci. Agric. Sin. 2005, 38,
2014–2022.
12. Zhao, X.M.; Zeng, Z.H. The research of the pesticidal activity on different Peganum harmala
extractions (in Chinese). Chin. Agric. Sci. Bull. 2005, 21, 278–279.
13. Weng, Q.F.; Zhong, G.H.; Wang, W.X.; Luo, J.J.; Hu, M.Y. Effectiveness of plant extracts for the
control of Meloidogyne incognita (in Chinese). J. South Chin. Agric. Univ. 2006, 27, 55–60.
14. Liu, J.X.; Hu, H.B.; Zhao, G.L. Effects of alkaloid of Peganum multisectum Bobr on seed
germination of Cucumber (Cucumis sativus L.). Plant Physiol. Commun (in Chinese). 2007, 43,
250–254.
15. Sodaeizadeh, H.; Rafieiolhossaini, M.; Havlík, J.; van Damme, P. Allelopathic activity of
different plant parts of Peganum harmala L. and identification of their growth inhibitors
substances. Plant Growth Regul. 2009, 59, 227–236.
16. Sodaeizadeh, H.; Rafieiolhossaini, M.; van Damme, P. Herbicidal activity of a medicinal plant,
Peganum harmala L., and decomposition dynamics of its phytotoxins in the soil. Ind. Crops Prod.
2010, 31, 385–394.
17. Love, B.E. Synthesis of β-carbolines. A review. Org. Prep. Proced. Int. 1996, 28, 1–64.
18. Silverman, B.D.; Daniel, E.P.; Mike P.; Isidore R. Comparative molecular moment analysis
(CoMMA). Perspect. Drug Discov. Des. 1998, 12–14, 183–196.
19. Guan, H.J.; Chen, H.S.; Peng, W.L.; Ma, Y.; Cao, R.H.; Liu, X.D.; Xu, A.L. Design of
β-carboline derivatives as DNA-targeting antitumor agents. Eur. J. Med. Chem. 2006, 41, 1167–1179.
20. Cao, R.H.; Guan, X.D.; Shi, B.X.; Chen, Z.Y.; Ren, Z.H.; Peng, W.L.; Song, H.C. Design,
synthesis and 3D-QSAR of β-carboline derivatives as potent antitumor agents. Eur. J. Med. Chem.
2010, 45, 2503–2515.
21. Formagio, A.S.N.; Santos, P.R.; Zanoli, K.; Ueda-Nakamura, T.; Tonin, L.T.D.; Nakamura, C.V.;
Sarragiotto, M.H. Synthesis and antiviral activity of beta-carboline derivatives bearing a substituted
carbohydrazide at C-3 against poliovirus and herpes simplex virus (HSV-1). Eur. J. Med. Chem.
2009, 44, 4695–4701.
Sample Availability: Samples of all the compounds are available from the authors.
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