Synthesis and evaluation of indole derivatives as photosynthesis and plant growth inhibitors

Article abstract of DOI:10.1039/c8pp00506k

Indole derivatives were synthetized based on the Fischer indole methodology using different phenyl hydrazine hydrochlorides and either cyclohexanone or 2-butanone. The pre- and post-emergent herbicidal activities were evaluated against Ipomoea grandifolia. A carbazole, 6-chloro-2,3,4,9-tetrahydro-1H-carbazole (3b), decreased the PI_abs parameter by 32% and increased the cross-section related parameters, indicating the inactivation of the reaction center on photosystem II. Compound 3b acts as a post-emergent herbicide prototype since dry biomass was reduced by 50%, corroborating the fluorescence results. Comparing instead with a germination experiment, 2,3,4,9-tetrahydro-1H-carbazole (3a) was found to be the most effective agent, inhibiting seed germination by 22% and decreasing root length by 50%. The tetrahydrocarbazoles showed better results than indole derivatives potentially due to the presence of methylene groups at structures, which increase the compounds' lipophilicity and may facilitate their access to the plant. In addition, electron withdrawing groups on the aromatic ring were found to correlate with increased herbicide activity. Further optimization of this series towards the development of herbicides is ongoing.

Full text of DOI:10.1039/c8pp00506k

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Photobiological Sciences
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Synthesis and evaluation of indole derivatives as
photosynthesis and plant growth inhibitors
Cite this: DOI: 10.1039/c8pp00506k
a
b
b
Mylla Cristie da Silva Mendes, Bruno Rodrigues Fazolo, Jéssica Maria de Souza,
b
b
Leonardo Gomes de Vasconcelos,
Marcos Antônio Soares,
and Lucas Campos Curcino Vieira
Paulo Teixeira de Sousa Junior,
b
c
b
Evandro Luiz Dall’Oglio,
Olívia Moreira Sampaio
d
*
Indole derivatives were synthetized based on the Fischer indole methodology using different phenyl
hydrazine hydrochlorides and either cyclohexanone or 2-butanone. The pre- and post-emergent herbici-
dal activities were evaluated against Ipomoea grandifolia. A carbazole, 6-chloro-2,3,4,9-tetrahydro-1H-
carbazole (3b), decreased the PIabs parameter by 32% and increased the cross-section related parameters,
indicating the inactivation of the reaction center on photosystem II. Compound 3b acts as a post-
emergent herbicide prototype since dry biomass was reduced by 50%, corroborating the fluorescence
results. Comparing instead with a germination experiment, 2,3,4,9-tetrahydro-1H-carbazole (3a) was
found to be the most effective agent, inhibiting seed germination by 22% and decreasing root length by
50%. The tetrahydrocarbazoles showed better results than indole derivatives potentially due to the pres-
Received 6th November 2018,
Accepted 12th March 2019
ence of methylene groups at structures, which increase the compounds’ lipophilicity and may facilitate
their access to the plant. In addition, electron withdrawing groups on the aromatic ring were found to
correlate with increased herbicide activity. Further optimization of this series towards the development of
herbicides is ongoing.
DOI: 10.1039/c8pp00506k
rsc.li/pps
The photosynthetic apparatus has been used to evaluate the
effects on plant physiology caused by environmental change.
1
. Introduction
Herbicides are a wide variety of chemical classes acting on In this way, chlorophyll a (Chl a) fluorescence has become an
several physiological processes, including metabolic energy important technique in ecophysiology studies since it is a non-
transfer, in plants, which inhibit the growth and development invasive measurement of photosystem II (PSII) activity, provid-
1
,2
11
of the plants. As these effects lead to the death of plants, ing useful information through the JIP test. Transient ana-
herbicides are used broadly for weed control, which is impor- lysis is a very useful tool to investigate the photosynthetic
1
2
tant for the environment, human health and food supply. response and adaptive ability to a wide range of stressors.
However, the prolonged use of these operates as a selection The OJIP transients are rich in information and can be used to
process that has led to the emergence of herbicide-resistant derive many parameters, which are used to quantify the PSII
3
13
weeds.
Thus, it is of critical importance to weed management that
behavior/activity.
Indole alkaloids represent privileged structures in medicine,
new selective herbicides are developed that have a potent and agrochemicals, pigments and materials science. The indole
broad coverage of weed species. Furthermore, the selective nucleus, a heteroaromatic scaffold containing a pyrrole ring
herbicides need to be safe to the target crop, environment and fused to a benzene ring, is a very important pharmacodynamic
humans. In this context, natural products, as well as synthetic core and indole derivatives have been used in a variety of bio-
14
compounds, have been investigated as candidates for potential logical applications, including as anti-depressants, as anti-
4
–10
15
16
herbicides.
cancer agents, in treating Alzheimer’s disease, as antimicro-
bials,
1
7,18
19
and as pre- and post-emergent herbicides. Due to
their electron donating ability, indole derivatives are also used
a
Forest Engineering Faculty, Federal University of Mato Grosso, Cuiabá-MT, Brazil
Chemistry Department, Federal University of Mato Grosso, Cuiabá-MT, Brazil
as building blocks for electroluminescent materials, such as
b
c
20,21
polymers with electrical and thermal properties.
Therefore,
Botany and Ecology Department, Bioscience Institute, Federal University of
Mato Grosso, Cuiabá, Mato Grosso, Brazil
considering the electronic properties of indole derivatives, it is
pertinent to study the effects of these compounds as electron
transport chain inhibitors on the photosynthesis process.
d
Engineering Institute/Chemistry, Federal University of Mato Grosso,
Várzea Grande-MT, Brazil. E-mail: lucascurcino@ufmt.br; Tel: +556536158798
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cooled to 0 °C. To the cooled solution was added dropwise
sodium nitrite (7.24 mmol in 4.0 mL water) under stirring at
the same temperature and stirred for 10 min. Subsequently, a
2 2
solution of SnCl ·2H O (0.026 mol in 3.5 mL HCl (37%)) was
added dropwise. The resulting suspension was stirred at 0 °C
for 30 min. The precipitate was filtered, washed with diethyl
ether (2 × 10 mL) and dried under vacuum. The crude product
was used without further purification.
Fig. 1 Indole derivatives.
In this work, we set out to synthesise a family of indole 2.3. General method for the synthesis of compounds 3a–d
derivatives (Fig. 1). These were then to be screened in pre- and and 4a–d
post-emergent herbicide assays for the parameters photo-
synthesis, plant growth and germination inhibition.
23
According to a modified literature procedure, to a sus-
pension of substituted phenylhydrazine hydrochloride
(
1.25 mmol) and ketone (1.25 mmol) in water (3 mL) was
added H SO (0.7 mmol). The mixture was heated at 100 °C for
2
4
2
. Experimental
90 min. After the reaction was complete, the mixture was
cooled to 0 °C, and the precipitate was filtered off, washed
with water and dried under reduced pressure to provide the
crude product. Further purification was achieved by flash
column chromatography, eluting with hexane : ethyl acetate
2
.1 General
Unless otherwise noted, all commercially available reagents
were purchased from Aldrich Chemical Co. and used without
further purification. Column chromatography was performed
using Merck silica gel (230–400 mesh). Thin layer chromato-
graphy (TLC) was performed using Merck silica gel GF254 of
(
9 : 1) to yield the desired products.
.3.1. 2,3,4,9-Tetrahydro-1H-carbazole (3a). Yield: 45%.
24
2
25
Brown solid. Melting point: 122 °C, lit.: 118–120 °C. IR (KBr
0
.25 mm thickness. For visualization, TLC plates were devel-
−1
1
pellet, cm ): 3394, 3047, 2924, 2846, 1465, 1460, 740. H NMR
DMSO-d , 500 MHz) δ: 1.76–1.85 (m, 4H), 2.59–2.61 (m, 2H),
.67–2.69 (m, 2H), 6.87–6.91 (m, 1H), 6.94–6.97 (m, 1H), 7.21
d, J = 7.9 Hz, 1H), 7.30 (d, J = 7.6 Hz, 1H), 10.56 (s, 1H).
oped with either iodine vapor or acidic vanillin.
H Nuclear magnetic resonance ( H NMR) and C NMR
spectra were recorded on a Bruker Ascend™ 500 MHz instru-
(
2
(
6
1
1
13
ment. The coupling constants (J) are given in hertz (Hz) and 13
C NMR (DMSO-d
6
, 125 MHz) δ: 20.5, 22.7, 22.8, 22.9, 107.9,
10.4, 117.0, 117.8, 119.9, 127.2, 134.3, 135.5.
.3.2. 6-Chloro-2,3,4,9-tetrahydro-1H-carbazole (3b).
Yield: 62%. Pale yellow solid. Melting point: 162 °C, lit.:
chemical shifts are reported in parts per million (ppm), refer-
enced to the internal standard tetramethylsilane (TMS). The
abbreviations s, bs, d, t, q, m, and dd refer to singlet, broad
1
24
2
singlet, doublet, triplet, quartet, multiplet, and doublet of
1
25
−1
62–163 °C. IR (KBr pellet, cm ): 3402, 2939, 2846, 1465,
doublets, respectively. All NMR spectra were obtained with
CDCl or DMSO-d .
1
3
1435, 802. H NMR (CDCl , 500 MHz) δ: 1.83–1.93 (m, 4H),
3
6
2
8
.63–2.66 (m, 2H), 2.70–2.73 (m, 2H), 7.04 (dd, J = 1.9 Hz,
.5 Hz, 1H), 7.16 (d, J = 8.4 Hz, 1H), 7.40 (d, J = 1.9 Hz, 1H).
Fourier transform infrared spectroscopy (FTIR) analysis was
performed on a Shimadzu Iraffinity-1 spectrophotometer. KBr 13
C NMR (CDCl
3
, 125 MHz) δ: 20.7, 20.7, 23.05, 23.08, 23.2,
pellets were prepared by mixing the compounds (1 mg) with
pure and anhydrous KBr (100 mg). The qualitative analyses
were carried out using the following parameters: measured
1
10.0, 111.2, 117.3, 121.0, 124.7, 129.0, 133.9, 135.7.
26
2.3.3. 6-Bromo-2,3,4,9-tetrahydro-1H-carbazole (3c). Yield:
26
5
7%. Pale brown solid. Melting point: 158 °C, lit.: 152–154 °C.
mode (% transmittance), apodizaiton (Happ_Genzel), number
−1
IR (KBr pellet, cm ): 3402, 2931, 2908, 2839, 1573, 1465, 1435,
7
of scans (200), resolution (16), range (400–4000 cm− ) and
1
1
94. H NMR (DMSO-d , 500 MHz) δ: 1.74–1.84 (m, 4H),
6
gain (1). The spectra acquisition was done employing IRSolution
2
.56–2.58 (m, 2H), 2.67–2.69 (m, 2H), 7.06 (dd, J = 1.9 Hz,
software (version 1.50). The background obtained from KBr
8
.3 Hz, 1H), 7.18 (d, J = 8.3 Hz, 1H), 7.46 (d, J = 1.8 Hz, 1H),
pellets was automatically subtracted from the sample spectra.
1
13
0.85 (s, 1H). C NMR (DMSO-d , 125 MHz) δ: 20.3, 22.66,
Melting points were recorded on a PFM-II/MS Tecnopon
2
6
2.69, 22.7, 108.0, 110.5, 112.3, 119.3, 122.2, 129.1, 134.2, 136.3.
melting point apparatus.
27
2.3.4. 2,3,4,9-Tetrahydro-1H-carbazole-8-carboxylic acid (3d).
Compound 5 was purchased from Aldrich Chemical Co.
Yield: 71%. White solid. Melting point: 201–203 °C, lit.:
(CAS number: 120-72-9).
28
−1
2
1
5
01–203 °C. IR (KBr pellet, cm ): 3464, 3062, 2924, 2846,
Chl a fluorescence transients were measured using a
1
665, 1581, 1465, 1435, 1265, 748. H NMR (DMSO-d
00 MHz) δ: 1.77–1.82 (m, 4H), 2.61–2.64 (m, 2H), 2.74–2.76
6
,
Hansatech Handy-Plant Efficient Analyzer; a three LED array
allowed for illumination with 650 nm continuous light
(
(
(
m, 2H), 7.01 (t, J = 7.6 Hz, 1H), 7.59 (d, J = 7.6 Hz, 1H), 7.62
d, J = 7.3 Hz, 1H), 10.55 (s, 1H), 12.77 (s, 1H). C NMR
−
2 −1
(
gain 0.7, intensity 2830 μmol photons m
s
).
13
DMSO-d , 125 MHz) δ: 20.4, 22.71, 22.79, 22.87, 108.4, 112.5,
6
2
.2. General method for the synthesis of compounds 2a–d
1
17.5, 122.3, 122.6, 128.8, 134.7, 136.2, 168.1.
2
2
24
According to a modified literature procedure, a solution of
2.3.5. 2,3-Dimethyl-1H-indole (4a).
Yield: 34%. White
2
5
substituted phenyl amine (0.16 mol) in HCl (6.5 mL, 37%) was solid. Melting point: 112 °C, lit.: 104–106 °C. IR (KBr pellet,
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cm− ): 3394, 2916, 2862, 1627, 1458, 1435, 740. H NMR negative control (DMSO), 3-(3,4-dichlorophenyl)-1,1-dimethyl-
1
1
(
(
CDCl , 500 MHz) δ: 2.24 (s, 3H), 2.38 (s, 3H), 7.07–7.13 urea (DCMU) as the positive control and experimental
3
m, 2H), 7.26–7.27 (m, 1H), 7.47–7.49 (m, 1H), 7.67 (bs, 1H). samples, which were manually sprayed with 3a–d, 4a–d and 5
1
3
C NMR (CDCl
19.0, 120.8, 129.4, 130.5, 135.2.
.3.6. 5-Chloro-2,3-dimethyl-1H-indole (4b). Yield: 58%.
3
, 125 MHz) δ: 8.4, 11.5, 107.1, 109.9, 117.9, at 150 and 450 µM. Each concentration was tested on three
1
sets of three plants.
2
9
2
Chl a fluorescence was measured in the leaves of the
3
0
Pale brown solid. Melting point: 144 °C, lit.: 138–140 °C. IR control plant and those sprayed with 3a–d, 4a–d and 5 at 150
KBr pellet, cm− ): 3402, 2916, 2854, 1573, 1465, 1435, 802. and 450 µM. After 1, 7 and 14 days of treatment, the leaves
1
(
1
H NMR (CDCl
3
, 500 MHz) δ: 2.19 (s, 3H), 2.36 (s, 3H), 7.06 were adapted to the dark for 30 min and then were excited
(
1
1
dd, J = 1.9 Hz, 8.5 Hz, 1H), 7.15 (d, J = 8.3 Hz, 1H), 7.43 (d, J = with light from an array of three light-emitting diodes deliver-
1
3
−2 −1
.9 Hz, 1H), 7.71 (bs, 1H). C NMR (CDCl , 125 MHz) δ: 8.3, ing 3000 µmol m
s
of red light (650 nm). The Chl a fluo-
rescence induction curves were measured at room temperature
.3.7. 5-Bromo-2,3-dimethyl-1H-indole (4c). Yield: 59%. with a portable Hansatech Fluorescence Handy PEA (plant
3
1.5, 106.9, 110.9, 117.4, 120.9, 124.6, 130.5, 132.3, 133.4.
2
4
2
3
1
Brown solid. Melting point: 138 °C, lit.: 137–138 °C. IR (KBr efficiency analyzer) apparatus.
pellet, cm− ): 3394, 2916, 2854, 1643, 1485, 1427, 794. H NMR
1
1
To evaluate the effect of 3a–d, 4a–d and 5 in Ipomoea grandi-
, 500 MHz) δ: 2.11 (s, 3H), 2.29 (s, 3H), 7.05 (dd, J = folia on plant growth, after 14 days the root length (RL in cm),
.8 Hz, 8.3 Hz, 1H), 7.16 (d, J = 8.3 Hz, 1H), 7.49 (d, J = 1.8 Hz, shoot length (SL in cm), and shoot dry weight (SDW in mg)
(DMSO-d
6
1
1
1
1
3
H), 10.85 (s, 1H). C NMR (DMSO-d
04.9, 110.5, 112.0, 119.5, 122.1, 130.7, 133.2, 133.7.
.3.8. 2,3-Dimethyl-1H-indole-7-carboxylic acid (4d).
6
, 125 MHz) δ: 8.0, 11.1, were measured. RL and SL were calculated from the seed base
to the root and shoot tips, respectively, using a ruler (±0.1 cm).
SDW was determined by drying all the components in an oven
3
2
2
Yield: 63%. White solid. Melting point: 214–215 °C, lit.: at 60 °C until a constant mass was obtained and SDW was
3
3
−1
10
2
1
2
7
1
1
16–217 °C. IR (KBr pellet, cm ): 3556, 3464, 2916, 2854, measured using an analytical balance.
1
666, 1458, 1427, 933, 756. H NMR (DMSO-d , 500 MHz) δ:
.16 (s, 3H), 2.35 (s, 3H), 7.02 (t, J = 7.6 Hz, 1H), 7.62 (d, J = were placed in 9.0 cm Petri dishes containing 8.5 cm sheets of
.4 Hz, 2H), 10.54 (s, 1H), 12.83 (s, 1H). C NMR (DMSO-d
25 MHz) δ: 8.1, 11.1, 105.5, 112.3, 117.5, 122.5, 122.6, 130.4, 3a–d, 4a–d and 5 (50 µM and 100 µM), and DMSO and DCMU
2.4.3. Germination assay. Ten seeds of Ipomoea grandifolia
6
1
3
6
,
Whatman No. 1 filter paper and 15.0 mL of the solution with
33.2, 134.2, 168.1.
as negative and positive controls, respectively. We used three
Petri dishes for each treatment. Petri dishes were incubated in
a Biochemical Oxygen Demand chamber. The number of
2
.4. Herbicidal activities
2
.4.1. Chl a fluorescence measurements. Spinach leaves germinated seeds was counted daily at the incubation time,
were cut into 10 mm diameter discs and 10 of these discs were and each seed was considered to have germinated when the
1
0
placed with 20 mL of modified Krebs solution in a Petri dish radicle emerged.
(
(
(
9 cm diameter). A solution consisting of NaCl (115 mM), KCl
The germination rate (GR), the germination index (GI) and
the germination rate index (GRI) of Ipomoea grandifolia seeds
5.9 mM), MgCl (1.2 mM), KH PO (1.2 mM), Na SO
2
2
4
2
4
1.2 mM), CaCl (25 mM), and NaHCO (25 mM, pH = 7.4) was were determined. GR was calculated using the ratio of the final
2
3
added. After 12 h of incubation at room temperature, 3a–d, numbers of seed germination to the total numbers of seeds
a–d and 5 were added with dimethyl sulfoxide (DMSO) solu- when no new germination occurred after 7 days of incubation.
4
tions at different concentrations (150 and 450 µM) to each GI was calculated using the following equation: GI = ∑(Gi × I),
Petri dish and incubated for an additional 6 hours. Then, the where Gi is the number of germinations in I (the time after
3
4
discs were kept in the dark for 30 min. The maximum fluo- cultivation (day)). GRI was calculated using the following
3
5
rescence yield from the sample was obtained by 2 s irradiation. equation: GRI = ∑(Gi × I)/∑Gi. The radicular and shoot
DMSO was added in the control experiments in order to assess lengths of the growing seedlings were determined with the aid
the solvent effect; the volume of DMSO added was equivalent of a caliper.
to that used to dissolve compounds 3a–d, 4a–d and 5. OJIP
2.4.4. Statistical analysis. Plant growth and germination
transients were analyzed according to the JIP test. Compounds assays were performed in a completely randomized design.
were considered to be photosynthetic inhibitors if they showed Data were analysed using the statistical program SPSS 11.0,
a variation in the PIabs parameter of more than 10%.
including analysis of variance (ANOVA), Levene’s test for homo-
2
.4.2. Effect of 3a–d, 4a–d and 5 on plant growth and geneity of variance and normality, and Duncan’s multiple
photosynthesis. Ipomoea grandifolia seeds were placed in range test for differences between means in all tests.
plastic pots (top diameter, 10.5 cm; bottom diameter, 7.5 cm;
height, 7.0 cm) filled with approximately 100 g of a mixture of
8
0 : 20 w/w soil/vermiculite. All pots were watered every day,
3
. Results and discussion
maintained in a greenhouse at 25–30 °C and under normal
day/night illumination (12 h/12 h). Ipomoea grandifolia plants
3.1. Indole derivative synthesis
were selected by uniformity of size after 15 days of growth. The syntheses of the indole derivatives were based on the
Plants of similar size were separated into three groups: the Fischer indole methodology using different phenyl hydrazine
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1
13
hydrochlorides (2a–d) and either cyclohexanone or 2-buta- pounds were characterized by H NMR, C NMR, and FT-IR
none. Diazotization of substituted phenyl amines (1a–d) was spectroscopy, and the results corroborated literature data.
performed employing sodium nitrite in hydrochloric acid fol-
3
.2. Effect of 3a–d, 4a–d and 5 on Chl a fluorescence
lowed by a one-pot reduction reaction using stannous chloride
in hydrochloric acid to furnish 2a–d in good yields. The
Fischer indole reaction was then performed employing 2a–d,
2
2
transients
3.2.1 Semi in vivo assays. Indole derivatives showed
cyclohexanone or 2-butanone, sulphuric acid as catalyst and appreciable results in the Chl a fluorescence assay through
water as solvent. Eight indole derivatives (3a–d and 4a–d) were electron transport inhibition performed on spinach leaf discs
2
3
synthesised in low to moderate yields (Scheme 1). All com- (Fig. 2 and 3). All compounds demonstrated activity at 150
Scheme 1 Synthesis of indole derivatives 3a–d and 4a–d.
Fig. 2 Radar charts of the effects of 3a–b and 3d on Chl a fluorescence parameters calculated from the OJIP curve in spinach sheet discs at
1
50 µM and 450 µM.
Fig. 3 Radar charts of the effects of 4a, 4c–d and 5 on Chl a fluorescence parameters calculated from the OJIP curve in spinach sheet discs at
50 µM and 450 µM.
1
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and/or 450 μM concentrations, with the exception of 3c to the amount of active RCs (DI
0
/RC) increases because of a
4
2
and 4b, which showed no activity even at the elevated high dissipation of inactive RCs.
concentration. The increase of absorbed and trapped energy did not result
Compounds 3a, 3b, 3d, 4a and 4d showed a PIabs reduction in the increase in electron transport energy (ET /RC), but
0
at both concentrations (150 and 450 μM), while 4c only resulted in a sharp increase in DI /RC, suggesting that the
0
showed activity at 150 μM and 5 demonstrated inhibition energy was dissipated as heat. It was also a self-protection
activity at 450 μM compared to the control (DMSO). mechanism of leave discs by the stressed conditions in the
3
8
Compounds 3a, 3b and 3d reduced the PIabs parameter by presence of 3a, 3b and 3d.
6.6, 32.4 and 40.1%, respectively, at 150 μM, indicating stress The quantum yield parameters were not affected by 3a, 3b
in the photosynthetic process (Fig. 2). PIabs is one of the main and 3d at either concentration. The parameters K and K were
2
n
p
photosynthetic parameters evaluated; this is because it is the reduced in the presence of 3b by 22.4 and 17.7%, respectively,
most sensitive parameter for the detection and quantification and increased by 18.0 and 16.6%, respectively, in the presence
of the damage caused to plants. Furthermore, as the efficiency of 3d. The decrease indicates that the absorbed and trapped
of absorption, capture and transfer of PSII excitation energy, energy was not released from the system, and the increase
the PIabs provides a better definition of the effects of a stressful means that the energy was released in the form of heat or
1
0,36–39
environment.
transfer to other molecules. Thus, both compounds induce
JIP parameters may identify sensitive effects such as absorp- damage to the protein complexes of the plant.
3
6
tion and energy trapping as electron transport. Thus, to
Compounds 4a and 4d reduced the PIabs parameter by 21.9
identify the damage on the acceptor side of PSII, several para- and 14.1% (150 μM), and 45.4 and 15.0% at 450 μM, respect-
meters of the curve JIP were calculated (Fig. 2). Compounds ively (Fig. 3). Compound 5 only reduced the PIabs parameter at
3
a, 3b and 3d showed a significant increase in the rate of reac- 450 μM by 61.6% (Fig. 3). Furthermore, the increase of reaction
tion center (RC) being closed, as indicated by the increase in centre parameters (Abs/RC, TR /RC, Et /RC and DI /RC) by
M = dV/dt at 150 μM by 41.5, 53.0 and 64.0%, respectively, compound 4d, associated with the decrement of the number
0
0
0
0
0
−
suggesting that the reduction of QA to QA was higher of active PSII RC parameter (10RC/ABS) by 15.8%, demon-
than the control. The reduction of PIabs with the increase of strated its action on the D2 protein process.
M = dV/dt indicated that the damage to the photosynthetic
apparatus was irreversible.
Compounds 4a and 5 increased cross section parameters
(Abs/CS , RC/CS , DI /CS and PHI (D )), showing that these
0
0
0
0
0
0
0
Associated with these results, a significant variation is compounds inactivate the reaction centres, inhibiting the QA
observed in other parameters related to RC, providing infor- reduction process. The inhibition of electron transfer by 5
mation about the effect of the compounds in the electron corroborates the decrement of quantum yield (PSI
transport chain. Compounds 3a, 3b and 3d increased the para- which is associated with the decrease of Et /RC and Et
meters Abs/RC by 21.0, 12.0 and 25%, TR /RC by 22.2, 13.2 26.7 and 12.8, respectively, indicating that the electrons that
0
) by 20.8%,
0
0
/CS by
0
0
and 25.0%, Et
1
0 0
/RC by 20.4, 9.0 and 21.4% and DI /RC by 18.0, were trapped in the transport chain are limited to follow
8.0 and 23.6%, respectively. The increase of these parameters beyond the QA− site. The same behaviour was observed in 4a,
indicates that the energy that was absorbed by PSII was not which reduced the PSI0 and Et /RC parameters by 11.7 and
0
carried to the photosynthesis reactions, demonstrating that 20.1%, respectively (Fig. 3).
the energy absorbed by the photosystem was lost as heat,
emitted as fluorescence or transferred to other systems. In increased the cross section parameters RC/CS , Abs/CS , TR /
Compound 4c decreased the PIabs parameter by 20.4% and
4
0
0
0
0
this way, the increase of DI
RCs that have become inactive.
Compound 3b increased the cross-section (CS) related para-
meters Abs/CS , TR0/CS , Et /CS and DI /CS
0.8 and 18.0%, respectively, while 3a and 3d resulted in only in vivo assays in an Ipomoea grandifolia plant, a common
0 0 0 0 0 0
/Rc confirms a high dissipation of CS , ET /CS and DI /CS by 21.3, 23.2, 21.5, 18.2 and 28.3%,
4
1
respectively (Fig. 3), indicating the same behavior of 4a and 5.
3.2.2 In vivo assays. Compounds 3a–b, 3d, 4a, 4c–d and 5,
0
0
0
0
0
0
by 23.2, 24.9, which showed activity in semi in vitro assays, were evaluated by
4
3
2
4
4
a small variance in these parameters (Fig. 2). These results weed present in corn, soybeans and rice crops. The effects of
indicate that 3b may penetrate the spinach leaf discs, meaning indole derivatives (150 and 450 μM) were evaluated 7 and
damage to the QA redox process, which corroborates the effect 14 days after the compounds were sprayed on plants. All com-
of RC inactivation.
pounds showed the same behaviour all along the period of
The same pattern of the variation of parameter values 14 days at both concentrations (Fig. 4).
observed at 150 μM was verified at 450 μM (Fig. 2).
The PIabs parameter was increased on average by 70 to
Compounds 3a, 3b and 3d reduced the PIabs by 19.2, 35.0 and 125% by compounds 3b, 3d, 4a, 4d and 5 at both concen-
2
0 0
5.6% and increased the M = dV/dt by 17.0, 52.0 and 31.6% trations in 7 days. After 14 days, the increment of PIabs was
at 450 μM, respectively, indicating that at high concentrations, lower than that in 7 days, on average by 12 to 42%. This
these compounds also affect the photosynthetic apparatus. increase occurs as a compensation for the low photosynthetic
These results indicate that the average absorption (Abs/RC) capacity and initial stress adaptation caused by the com-
and trapping per active RC (TR
inactivation of some RCs, and the ratio of the total dissipation synthetic process generated reversible stress effects on PSII.
0
/RC) increase owing to the pounds, indicating that the plant efficiency on the photo-
39,40
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3.3. Dry biomass
Dry biomass of Ipomoea grandifolia plants was weighed after
1
4
4 days of treatment with 3a–b, 3d, 4c–d and 5 at 150 and
50 µM, in the absence of compounds (negative control) and
with 10 µM of DCMU (positive control) (Table 1).
All the compounds showed plant growth inhibition, except
3d and 4a. Compounds 3b and 4c–d inhibited plant growth by
50, 14, and 22% (150 μM), respectively. At 450 μM, the best
result was achieved for 3b, reducing the dry biomass by 43%.
These results suggest that the tetrahydrocarbazole derivatives
are better plant growth inhibitors than the indole derivatives,
maybe due to the high lipophilicity promoted by the CH2
groups and the presence of a chlorine atom at the aromatic
ring (Table 1, entry 3). The results of the dry biomass assay
corroborate the PSII inhibitor activities demonstrated by the
Chl a fluorescence assay, indicating that 3b has an action as a
post-emergent herbicide blocking the electron transfer process
at PSII in the plant.
Fig. 4 Radar chart of the effects of compounds 3a–b, 3d, 4a, 4c–d and
5
on Chl a fluorescence parameters calculated from the OJIP curve in
Ipomoea grandifolia plants at 150 µM (7 days).
The indole derivatives caused stress in the plants leading
to variations in the whole process, which are observed
through the other fluorescence parameters. A small vari-
0 0 0 0 0 0 0 0
ation in ET /CS , ET /RC, DI /CS , DI /RC and M = dV/dt
parameters confirms a failure in the electron transfer due to
the amount of reaction centers actives as seen in leaf disc
assays. The effects caused by the compounds are not high
when compared to the semi in vivo assay due to the
difficulty in achieving penetration of the compounds into
the living plant, and this can be explained by the limited
action of the compounds.
3.4 Assay of germination and root and stem growth
The phytotoxic activity of indole derivatives 3a–d, 4a–d and 5
on the germination and root and stem growth of Ipomoea
grandifolia plants was evaluated (Table 2). All of the com-
pounds affected seed germination development at 50 and
100 μM concentrations.
Compounds 3a and 3c at 50 μM inhibited seed germination
by 22% and 16% (Table 2 – entries 2 and 4), respectively.
Furthermore, both compounds decreased the germination
index and increased the germinated rate index compared to
the control.
Table 1 Effects of 3a–b, 3d, 4c–d and 5 on dry biomass production
Dry biomass (g) (%)
Although the activity of some indole derivatives does not
inhibit the germination rate, it can make difficult the germina-
tion process, leading to a decrease in the germination index,
Entry
Compound
150 μM
450 μM
1
2
3
4
5
6
7
8
9
Control
3a
3b
3d
4a
4c
4d
5
0.0602 ± 0.0030 (100)
0.0585 ± 0.0029 (97)
0.0301 ± 0.0015 (50)
0.0663 ± 0.0033 (110)
0.0623 ± 0.0031 (103)
0.0521 ± 0.0026 (86)
0.0473 ± 0.0023 (78)
0.0587 ± 0.0029 (97)
0.0124 ± 0.0006 (20)
0.0602 ± 0.0030 (100)
0.0442 ± 0.0022 (73)
0.0420 ± 0.0021 (67)
0.0618 ± 0.0030 (102)
0.0522 ± 0.0026 (87)
0.0439 ± 0.0021 (73)
0.0532 ± 0.0026 (88)
0.0472 ± 0.0023 (78)
4
5
possibly damaging the seedlings’ structure.
The seedlings treated with compounds 3a–d, 4a–d and 5
presented a reduction in root length (RL) compared to the
control; however, there was no statistically significant differ-
ence among them (p > 0.05), except for 3a and 5, which
decreased the root length by 49.6% (Table 2 – entry 2) and
43.6% (Table 2 – entry 10), respectively (p < 0.05).
DCMU
DCMU was used as a positive control at 50 μM.
Table 2 The germination rate (GR), germination speed index (GSI), germination rate index (GRI), root length (RL) and shoot length (SL) of Ipomoea
grandifolia seeds treated with 3a–d, 4a–d and 5
Entry Compound GR (%)
GSI
GRI
RL (cm)
4.79 ± 0.54 abc 5.37 ± 0.76 ab
SL (cm)
a
b
a
b
a
b
a
b
a
b
1
2
3
4
5
6
7
8
9
1
Control
3a
3b
3c
3d
4a
4b
4c
4d
100
100
21.30
20.50
20.50
20.80
18.70
20.50
19.45
18.50
20.50
21.50
14.00
3.00
3.02
3.00
3.02
3.00
3.00
3.01
3.00
3.00
3.05
3.00
3.00
3.02
3.04
3.00
3.01
3.02
3.00
3.02
3.00
6.94 ± 0.19 ab 6.23 ± 0.02 ab
3.86 ± 0.12 abc 6.19 ± 0.76 ab 6.55 ± 0.40 ab
78
96
84
93
93
96
93
93
100
96 16.40
100 20.50
96 17.70
100 19.70
96 19.70
92 20.20
100 19.70
100 19.70
100 17.20
4.56 ± 0.04 abc
4.59 ± 0.17 abc
5.95 ± 0.76 ab
5.71 ± 0.68 ab
4.75 ± 0.43 abc
4.96 ± 0.46 abc
4.47 ± 0.31 abc
5.90 ± 0.60 ab
2.70 ± 0.19 bc
5.59 ± 0.60 ab
2.71 ± 0.43 bc
6.53 ± 0.27 a
5.43 ± 0.82 ab
6.31 ± 0.11 ab
5.83 ± 0.97 ab
7.29 ± 0.31 a
6.90 ± 0.40 ab
6.27 ± 0.34 ab
6.47 ± 0.53 ab
5.96 ± 0.55 ab
6.96 ± 0.70 ab
6.04 ± 0.28 ab
6.43 ± 0.54 ab
6.15 ± 0.46 ab
6.20 ± 0.32 ab
5.77 ± 0.21 ab
5.78 ± 0.34 ab
6.64 ± 0.49 ab
5.63 ± 0.18 ab
4.92 ± 0.56 abc 6.78 ± 0.57 ab
3.17 ± 0.12 abc 5.10 ± 0.20 ab
0
5
5
a
b
0 μM. 100 μM, DCMU: GR (%) 70.71, GSI 14.8, GRI 3.02, RL (cm) 2.14 ± 0.43 c, SL (cm) 4.59 ± 0.66 b.
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Additionally, tetrahydrocarbazole compounds (3a–d)
showed better germination inhibitory activity than indole
derivatives (4a–d and 5), possibly due to the higher lipo-
philicity improved by methylene groups on the indole struc-
ture, which can promote its access through the plant cell
wall. The presence of electron withdrawing groups on the
aromatic ring of the indole framework also increased the
compounds’ activity, the chlorinated being the most active
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(Table 2 – entries 2 and 4).
Although 3b is a chlorinated compound, many studies
employing this molecule and its derivatives have reported
4
7–52
various biological activities,
which demonstrate their low
toxicity. However, additional experiments are required to
evaluate its toxicity to other organisms.
6 D. Torres-Romero, B. King-Díaz, I. A. Jiménez, B. Lotina-
Hennsen and I. L. Bazzocchi, Sesquiterpenes from
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T. A. M. Veiga, B. King-Díaz, A. S. F. Marques,
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4
. Conclusions
This work shows the synthesis of indole derivatives through
the Fischer reaction and their evaluation as photosynthesis
and plant growth inhibitors. The best result was obtained for
6
-chloro-2,3,4,9-tetrahydro-1H-carbazole (3b), which inacti-
vated the RC on PSII, causing damage to the QA redox process.
Compound 3b acts as a post-emergent herbicide prototype
since the dry biomass was reduced by 50%, corroborating the
fluorescence results. The best result in the germination assay
was achieved for 2,3,4,9-tetrahydro-1H-carbazole (3a), which
inhibited the seed germination by 22% and decreased the root
length by 49.6%. Tetrahydrocarbazoles showed better results
than indole derivatives, indicating that the presence of methyl-
ene groups at structures increases the compound’s lipo-
philicity and facilitates their access to the plant. In addition,
8 J. O. S. Varejão, L. C. A. Barbosa, E. V. V. Varejão,
C. R. A. Maltha, B. King-Díaz and B. Lotina-Hennsen,
Cyclopent-4-ene-1,3-diones: A new class of herbicides
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Chem., 2014, 62, 5772–5780.
9 L. Semelkova, K. Konecna, P. Paterova, V. Kubicek,
J. Kunes, L. Novakova, J. Marek, L. Naesens, M. Pesko,
K. Kralova, M. Dolezal and J. Zitko, Synthesis and bio-
logical evaluation of N-alkyl-3-(alkylamino)-pyrazine-2-
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the presence of electron withdrawing groups at the aromatic 10 O. M. Sampaio, M. M. de C. Lima, T. A. M. Veiga, B. King-
ring increases the herbicide activity. Then the optimization of
these features is a goal of our group in further development of
herbicides.
Díaz, M. F. G. F. Da Silva and B. Lotina-Hennsen,
Evaluation of antidesmone alkaloid as a photosynthesis
inhibitor, Pestic. Biochem. Physiol., 2016, 134, 55–62.
1 D. Q. Yang, Y. L. Luo, W. H. Dong, Y. P. Yin, Y. Li and
Z. L. Wang, Response of photosystem II performance and
antioxidant enzyme activities in stay-green wheat to cytoki-
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1
Conflicts of interest
There are no conflicts to declare.
12 M. Franić, V. Galić, M. Mazur and D. Šimić, Effects of
excess cadmium in soil on JIP-test parameters, hydrogen
peroxide content and antioxidant activity in two maize
inbreds and their hybrid, Photosynthetica, 2018, 56, 660–
Acknowledgements
669.
We gratefully acknowledge the FAPEMAT (grants 0217830/2017 13 R. J. Strasser, M. Tsimilli-Michael and A. Srivastava, in
and 0250685/2017), CNPq (grant 430089/2016-3) and UFMT for Chlorophyll a Fluorescence, 2004, pp. 321–362.
financial support and fellowships. This study was financed in 14 H. X. Ding, K. K.-C. Liu, S. M. Sakya, A. C. Flick and
part by the Coordenação de Aperfeiçoamento de Pessoal de
Nível Superior – Brasil (CAPES) – Finance Code 001.
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