Synthesis and insect antifeedant activity of plumbagin derivatives

Article abstract of DOI:10.1007/s00044-011-9559-7

Napthaquinones have received considerable interest in agricultural chemistry because of a novel action mode, extremely high activity against a broad spectrum of insects, low acute toxicity to mammals, and environmentally benign characteristics. A series of plumbagin derivatives (3a-3o) were synthesized under mild esterification conditions in straightforward procedure. The structures of all new compounds were confirmed by NMR, IR, MS, and HREIMS analyses. The plumbagin derivatives were screened for their insecticidal activities against tobacco caterpillar (Spodoptera litura) and castor semilooper (Achaea janata) using a no-choice laboratory bioassay. The results show that some of the title compounds exhibit excellent antifeedant activities against 3rd instar larvae of A. janata and S. litura. The improvement in antifeedant activity requires a reasonable combination of substituents in the parent structure, which provides some hints for further investigation on structure modification. Springer Science+Business Media, LLC 2011.

Full text of DOI:10.1007/s00044-011-9559-7

MEDICINAL
CHEMISTRY
RESEARCH
Med Chem Res (2012) 21:578–583
DOI 10.1007/s00044-011-9559-7
ORIGINAL RESEARCH
Synthesis and insect antifeedant activity of plumbagin derivatives
•
K. Rajendra Prasad K. Suresh Babu R. Ranga Rao
•
•
•
G. Suresh K. Rekha J. Madhusudana Murthy
•
•
•
P. Usha Rani J. Madhusudana Rao
Received: 18 November 2010 / Accepted: 11 January 2011 / Published online: 29 January 2011
Ó Springer Science+Business Media, LLC 2011
Abstract Napthaquinones have received considerable
interest in agricultural chemistry because of a novel action
mode, extremely high activity against a broad spectrum of
insects, low acute toxicity to mammals, and environmen-
tally benign characteristics. A series of plumbagin deriva-
tives (3a–3o) were synthesized under mild esterification
conditions in straightforward procedure. The structures of
all new compounds were confirmed by NMR, IR, MS, and
HREIMS analyses. The plumbagin derivatives were
screened for their insecticidal activities against tobacco
caterpillar (Spodoptera litura) and castor semilooper
(Achaea janata) using a no-choice laboratory bioassay. The
results show that some of the title compounds exhibit
excellent antifeedant activities against 3rd instar larvae of
A. janata and S. litura. The improvement in antifeedant
activity requires a reasonable combination of substituents
in the parent structure, which provides some hints for
further investigation on structure modification.
Introduction
The severe damage caused to the ecology and environment
as well as human health due to the usage of complex
chemical synthetic pesticides necessitated a shift to natural
crop protection and nourishment. Plants produce a diverse
range of secondary metabolites such as terpenoids, alka-
loids, polyacetylenes, flavonoids, quinones, and sugars as a
part of their defence mechanism against insects. Among
these classes, naphthaquinones, in particular, 5-hydroxy-
1,4-naphthaquinones such as plumbagin and juglone, are
important class of natural products that are extremely
useful for the development of potent agrochemicals in view
of their high abundance and relatively non toxic nature.
A literature precedence revealed that plumbagin isolated
from the Plumbago zeylanica possesses significant bio-
logical activities such as antimicrobial (Didry et al., 1994),
cytotoxic (Nguyen et al., 2004), antimalarial (Likhitwita-
yawuid et al., 1998), antifilaricidal (Mathew et al., 2002),
and antiprotozoal properties (Kayser et al., 2000). The
naphthaquinone skeletons with high abundance and
favorable structural features form the useful models for the
development of the potent antifeedants. Previously, it was
illustrated that the ingestion of the crude aqueous methanol
extracts of Plumbago zeylanica and its derivatives caused
failure of moulting cycle in another lepidopteran insect,
Bombyx mori (silk worm) (Kubo et al., 1983).
Keywords Plumbagin ꢀ Amines ꢀ Spodoptera litura ꢀ
Achaea janata ꢀ Insect antifeedant activity
K. Rajendra Prasad ꢀ K. Suresh Babu ꢀ R. Ranga Rao ꢀ
G. Suresh ꢀ K. Rekha ꢀ J. Madhusudana Rao (&)
Division of Organic Chemistry-I, Natural Product Laboratory,
Indian Institute of Chemical Technology, Tarnaka,
Hyderabad 500 607, India
As part of the ongoing program in the field of insecti-
cidal drugs (Sreelatha et al., 2010), the authors recently
reported a series of plumbagin derivative, with an amino
acid moiety as a new class of insecticidal agents (Sreelatha
et al., 2009). Encouraged by these reports, the authors
developed an idea that the introduction of an amine by
substituting the hydrogen 3rd position could improve bio-
logical properties and decrease resistance. Therefore, in a
e-mail: janaswamy@iict.res.in
J. Madhusudana Murthy ꢀ P. Usha Rani
Biology Division, Indian Institute of Chemical Technology,
Tarnaka, Hyderabad 500 607, India
123

Med Chem Res (2012) 21:578–583
579
Scheme 1 Synthesis of
plumbagin derivatives
OMe
O
O
OH
O
O
OMe
O
H
N
Primary Amines
Ag 2
O
R
CH3I
Ethanol.
CH 3 RT, 30min
CH3
CH3
RT, 6 hrs
O
1
(3a-3o)
2
3a. R = Ethyl
3l. R = Benzyl
3m . R = 4F-Benzyl
3b . R = Propyl
3c. R = n-Butyl
3d. R = n-Hexyl
3e. R = n-Octyl
3n . R = 4methoxy-Benzyl
3o. R = 4tri flouromethyl- Benzyl
3f
. R = Nonyl
3g
3h
3i.
3j.
3k
. R = Decyl
. R = DoDecyl
R = Deca Hexyl
R = Olleyl
. R = Allyl
search for new insecticides with low environmental impact
and improved profiles, a series of novel plumbagin deriv-
atives containing long chain and aromatic amines were
designed and synthesized (Scheme 1). In the present
investigation, quinine moiety was kept unchanged because
it is the characteristic structural requirement for activity. In
this article, the authors describe the synthesis and evalua-
tion of insect antifeedant activity of plumbagin derivatives
in the continuation of the search for new potent insecticidal
agents for Achaea janata and Spodoptera litura.
Table 1 Antifeedant effect of plumbagin and their derivatives 3a–3o
against Achaea janata and Spodoptera litura by leaf disk method
Compound
ED50 (95% FLa), lg/cm2
A. janata
S. litura
3a
24.41 (21.05–27.78)
[500
[500
3b
[500
3c
[500
64.08 (59.71–69.65)
278.34 (165.39–1209.07)
[500
3d
73.31 (59.29–104.54)
44.76 (35.59–63.39)
24.04 (22.95–25.08)
30.25 (24.61–36.82)
59.62 (50.81–71.02)
64.23 (48.86–61.00)
26.49 (22.65–31.68)
13.51 (7.300–18.19)
[500
3e
3f
32.50 (28.46–68.42)
31.109 (26.69–236.620)
[500
3g
Results and discussion
3h
3i
16.77 (5.32–29.37)
180.36 (121.64–860.72)
31.22 (18.68–79.42)
[500
The reaction sequence employed for the synthesis of the
title compounds is shown in Scheme 1. Initially, plumba-
gin was converted to its methyl ether 2 in 85% yield
through reaction with MeI in the presence of Ag2O in
dry dichloromethane. Michael addition of 5-O-methyl
plumbagin with various amines at room temperature using
ethanol as solvent afforded the targeted products. It should
be noted that previous studies have yielded a limited series
of plumbagin derivatives with amino acid moiety as the
core structure. In the current studies, it was decided to
examine the importance of the aliphatic amines as well as
the aromatic amines substitution pattern of at 3rd position
in plumbagin. Thus, all the 15 derivatives of plumbagin
were examined for their antifeedant activities against
A. janata and S. litura using the conventional no-choice
disk method. The results of the bioassays are given in
Table 1, which indicate that one of the title compounds
3a–3o exhibited moderate antifeedant activity against the
test insects, A. janata and S. litura, when compared to the
plumbagin and displayed 10–500 times less potency than
the standard, azadirachtin. The title compounds 3k and 3o
have shown potent antifeedant activity against A. janata.
Similarly, compounds 3f, 3g, 3i, and 3k displayed higher
antifeedancy than the plumbagin against S. litura larvae. It
3j
3k
3l
3m
51.091 (42.73–62.86)
[500
302.32 (174.78–1509.03)
[500
3n
3o
21.82 (19.43–23.58)
23.97 (12.33–34.12)
0.72 (0.64–0.79)
[500
Plumbagin
Azadirachtin
a
43.71 (28.42–72.36)
0.89 (0.54–1.39)
Fiducial limits, ED50 (concentrations causing 50% AFI)
was noticed that in the series of aliphatic amine derivatives,
compound with decahexyl chain displayed potent activity
against S. litura, and replacing the aliphatic chain with the
aromatic amines (compounds 3k–3o) resulted in a drastic
loss of antifeedant activity against both insect species, i.e.,
A. janata and S. litura. Overall, these results imply that the
mode of perception as well as the structure–activity rela-
tionship of the plumbagin analogues differs considerably
among the insect species examined in this study. However,
some of these compounds were highly promising as anti-
feedants against the two prominent agricultural pests, and
the future evaluation of the other pest species susceptibility
is likely to yield better pest management compounds. It is
123

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Med Chem Res (2012) 21:578–583
intriguing that, though the test insects belong to the same
order, i.e., Lepidoptera, the biological activity of the
derivatives differed. The reason, perhaps, is the genetic
variability of each genera. Both insects belong to different
genera as well as different feeding habitats: S. litura is a
polyphagous pest that can feed on any plant, and A. janata
being monophagous has restricted feeding on limited spe-
cies of plants.
was (70 g) chromatographed over silica gel (60–120 mesh)
and eluted with n-hexane/ethyl acetate combinations of
increasing polarity. Plumbagin (12 g) was obtained by
elution with n-hexane/ethyl acetate, 99:1.
General procedure for the synthesis of compound 2
To a solution of plumbagin (1) (0.2 g, 1.0638 mmol) in
dichloromethane (10 ml) at room temperature was added
CH3I (1.39 mmol) and freshly prepared Ag2O (0.05 mmol).
The resultant mixture was stirred for 6 h at room tempera-
ture. After completion of the reaction (monitored by TLC),
the reaction mixture was filtered, and then the filtrate was
concentrated to dryness. The residue thus obtained was
purified by column chromatography with the elution of
n-hexane/ethyl acetate, 90:10, to afford 5-O-methyl
plumbagin (2) as yellow needles (Dinda et al., 1998).
Conclusion
In conclusion, it was observed that the introduction of the
aliphatic and aromatic amines to the naphthaquinone
moiety causes a significant increase in the antifeedant
activity. Aliphatic amines were found to be more effective
than those of aromatic amines. On the basis of the results
observed, hexadecyl amine could be identified as the best
possible side chain among the amines screened to the pests,
S. litura and A. janata. This study has been carried out only
with simple amines; further study in this regard with var-
ious substituted amines will throw more light on the effi-
cacy of these compounds as potential antifeedants.
General procedure for the synthesis
of compound (3a–3o)
To a solution of 5-O-methyl plumbagin (2) (1 mmol) in
ethanol (10 ml) was added dropwise primary amines
(1 mmol) at room temperature. The resulting red-colored
solution was stirred for 30 min at room temperature. The
reaction was monitored by TLC, and after completion, the
reaction mixture was concentrated to dryness. The residue,
was purified by column chromatography using n-hexane/
ethyl acetate, 85:15, to yield the Michael adduct (3a–3o) as
red color powder with the yields of 75–90%.
Experimental
General
1H and 13C spectra were measured on a Bruker 300 MHz
spectrometer using tetramethylsilane as an internal stan-
dard. Mass spectra were recorded on Agilent LC/MSD trap
SL 1100 series with a 70 eV (ESI probe) and the infrared
spectra on a Thermo Nicolet Nexus 670 FTIR spectrome-
ter. Melting points were measured on a Fischer Scientific
melting point apparatus and were uncorrected. The syn-
thetic compounds were purified by column chromatogra-
phy using 60–120 mesh size silica gel (Merck). Thin layer
chromatography (TLC) involved the use of precoated silica
gel 60 F254 TLC plates of Merck. The optical rotations
were measured on Jasco Dip 360 digital Polarimeter.
3-(Ethyl amino)-5-methoxy-2-methylnaphthalene-1,4-dione
(3a): red color liquid. IR(KBr)mmax: 3435 (NH), 2966, 2925,
1
1664 cm-1. H NMR (300 MHz, CDCl3): d 1.27 (t, 3H,
J = 6.9 Hz, 7.1 Hz, 30-CH3), 1.50–1.70 (brs, NH, 1H), 2.21
(s, 3H, 2-CH3), 3.59 (q, 2H, J = 7.1 Hz, H-20), 3.99 (s, 3H,
5-OCH3), 7.14 (d, 1H, J = 8.5 Hz, H-8), 7.61 (t, 1H,
J = 7.9 Hz, 8.1 Hz, H-6), 7.78 (d, 1H, J = 7.5 Hz, H-7).
13C NMR (75 MHz, CDCl3): d 10.88, 16.10, 40.22, 56.34,
110.10, 115.51, 118.02, 119.08, 135.49, 135.96, 147.13,
159.55, 181.16, 183.19. HR-ESIMS Calcd. for C14H15NO3
(M ? H): 246.1125. Found: 246.1132.
5-Methoxy-2-methyl-3-(propylamino)naphthalene-1,4-dione
Extraction and isolation of plumbagin
(3b): mp: 60°C. IR(KBr)mmax: 3439, 2924, 2358, 1658 cm-1
.
1H NMR (300 MHz, CDCl3): d 0.99 (t, 3H, J = 7.3 Hz,
40-CH3), 1.26 (t, 2H, J = 7.1 Hz, H-30), 1.70–1.75 (brs, NH,
1H), 2.20 (s, 3H, 2-CH3), 3.51 (t, 2H, J = 6.9 Hz, 7.1 Hz,
H-20), 3.99 (s, 3H, 5-OCH3), 7.14 (d, 1H, J = 8.3 Hz, H-8),
7.62 (t, 1H, J = 7.9 Hz, 8.3 Hz, H-6), 7.78 (d, 1H,
J = 7.5 Hz, H-7). 13C NMR (75 MHz, CDCl3): d 10.99,
14.41, 24.05, 47.14, 56.33, 109.93, 115.45, 117.52, 119.07,
135.00, 135.52, 147.13, 159.53, 181.12, 183.14. HR-ESIMS
Calcd. for C15H18NO3(M? ? H): 260.1281. Found:
260.1267.
The roots of Plumbago zeylanica also known as Nila chi-
tramula (Isman et al., 1990) were collected during the
August–September 2005 from Tirumala forest, Tirupati,
Andhra Pradesh, India. A voucher specimen was deposited
at the herbarium of Indian Institute of Chemical Technol-
ogy, Hyderabad, India. The shade-dried roots of Plumbago
zeylanica were powdered in a pulvarizer (10 kg) and
extracted with chloroform/methanol, 1:1 followed by the
concentration under reduced pressure. The resulting extract
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Med Chem Res (2012) 21:578–583
581
3-(Butylamino)-5-methoxy-2-methylnaphthalene-1,4-dione
1
2H, H-30), 2.20 (s, 3H, 2-CH3), 3.53 (q, 2H, J = 6.7 Hz, H-20),
4.00 (s, 3H, 5-OCH3), 5.87–5.95 (brs, NH, 1H), 7.14 (d, 1H,
J = 8.4 Hz, H-8), 7.62 (t, 1H, J = 7.9 Hz, 8.1 Hz, H-6), 7.78
(d, 1H, 7.5 Hz, H-7). 13C NMR (75 MHz, CDCl3): d 11.00,
14.10, 22.65, 26.64, 29.26, 29.48, 30.82, 31.84, 45.44, 56.34,
109.84, 115.44, 117.93, 119.08, 135.52, 135.99, 147.13, 159.53,
181.13, 183.13. HR-ESIMS Calcd. for C22H32NO3 (M? ? H):
358.2377. Found: 358.2370.
(3c): mp: 63°C. IR(KBr)mmax: 3467, 2922, 1648 cm-1. H
NMR (300 MHz, CDCl3): d 0.95 (t, 3H, J = 7.1 Hz, 7.3 Hz,
50-CH3), 1.36–1.48 (m, 2H, H-40), 1.56–1.65 (m, 2H, H-30),
1.71–1.73 (brs, NH, 1H), 2.21 (s, 3H, 2-CH3), 3.54 (t, 2H,
J = 6.7 Hz, 6.9 Hz, H-20), 3.99 (s, 3H, 5-OCH3), 7.14 (d, 1H,
J = 8.4 Hz, H-8), 7.62 (t, 1H, J = 7.7 Hz, 8.3 Hz, H-6), 7.78
(d, 1H, J = 7.7 Hz, H-7). 13C NMR (75 MHz, CDCl3): d
10.99, 13.71, 19.80, 32.84, 45.14, 56.34, 109.95, 115.48,
117.55, 119.08, 135.51, 136.00, 147.18, 159.56, 181.14,
183.15. HR-ESIMS Calcd. for C16H20NO3(M? ? H):
274.1438. Found: 274.1433.
3-(Dodecylamino)-5-methoxy-2-methylnaphthalene-1,4-
dione (3h): mp: 82°C. IR(KBr)mmax: 3451, 2921, 2853,
1
1662 cm-1. H NMR (300 MHz, CDCl3): d 0.88 (t, 3H,
J = 5.8 Hz, 6.9 Hz, 120-CH3), 1.20–1.36 (m, 18H,
H-40–110), 1.55–1.66 (m, 2H, H-30), 2.20 (s, 3H, 2-CH3),
3.53 (q, 2H, J = 6.6 Hz, H-20), 3.99 (s, 3H, 5-OCH3),
5.88–5.95 (brs, NH, 1H), 7.14 (d, 1H, J = 8.3 Hz, H-8),
7.62 (t, 1H, J = 7.9 Hz, 8.3 Hz, H-6), 7.78 (d, 1H, 7.5 Hz,
H-7). 13C NMR (75 MHz, CDCl3): d 10.98, 14.10, 22.65,
26.62, 29.26, 29.30, 29.47, 29.52, 29.58, 30.80, 31.87,
45.42, 56.32, 109.80, 115.42, 117.91, 119.05, 135.51,
135.96, 147.11, 159.51, 181.10, 183.10. HR-ESIMS Calcd.
for C24H36NO3(M? ? H): 386.2690. Found: 386.2697.
3-(Hexadecylamino)-5-methoxy-2-methylnaphthalene-1,4-
dione (3i): mp: 84°C. IR(KBr)mmax: 3430, 2921, 2851,
1662 cm-1. 1H NMR (300 MHz, CDCl3): d 0.88 (t, 3H, J =
6.0 Hz, 6.9 Hz, 170-CH3), 1.21–1.39 (m, 26H, H-40–160),
1.53–1.62 (m, 2H, H-30), 2.20 (s, 3H, 2-CH3), 3.53 (t, 2H,
J = 6.9 Hz, H-20), 3.99 (s, 3H, 5-OCH3), 5.85–5.98 (brs,
NH, 1H), 7.14 (d, 1H, J = 8.4 Hz, H-8), 7.62 (t, 1H,
J = 7.7 Hz, 8.3 Hz, H-6), 7.78 (d, 1H, 7.5 Hz, H-7). 13C
NMR (75 MHz, CDCl3): d 11.00, 14.11, 22.68, 26.66, 29.29,
29.35, 29.49, 29.55, 29.66, 30.84, 31.92, 45.47, 56.36,
109.91, 115.49, 118.01, 119.10, 135.52, 136.03, 147.17,
159.57, 181.16, 183.16. HR-ESIMS Calcd. for C28H44NO3
(M? ? H): 442.3316. Found: 442.3317.
3-(Hexylamino)-5-methoxy-2-methylnaphthalene-1,4-dione
(3d): mp: 58°C. IR(KBr)mmax: 3446, 2926, 2359, 1663 cm-1
.
1H NMR (300 MHz, CDCl3): d 0.89 (t, 3H, J = 6.0 Hz,
6.9 Hz, 70-CH3), 1.25–1.45 (m, 6H, H-40–60), 1.56–1.66 (m,
2H, H-30), 1.70–1.73 (brs, NH, 1H), 2.21 (s, 3H, 2-CH3), 3.53
(t, 2H, J = 6.9 Hz, H-20), 3.99 (s, 3H, 5-OCH3), 7.14 (d, 1H,
J = 8.1 Hz, H-8), 7.62 (t, 1H, J = 7.9 Hz, 8.3 Hz, H-6),
7.78 (d, 1H, 7.5 Hz, H-7). 13C NMR (75 MHz, CDCl3): d
10.97, 13.96, 22.51, 26.31, 30.77, 31.43, 45.43, 56.33,
109.83, 115.45, 117.54, 119.05, 135.00, 135.51, 147.13,
159.53, 181.12, 183.13. HR-ESIMS Calcd. for C18H24NO3
(M? ? H): 302.1752. Found: 302.1751.
5-Methoxy-2-methyl-3-(octylamino)naphthalene-1,4-dione
1
(3e): red color liquid. IR(KBr)mmax: 3455, 1640 cm-1. H
NMR (300 MHz, CDCl3): d 0.88 (t, 3H, J = 6.0 Hz,
6.9 Hz, 90-CH3), 1.23–1.34 (m, 10H, H-40–80), 1.56–1.62
(m, 2H, H-30), 2.20 (s, 3H, 2-CH3), 3.53 (q, 2H,
J = 6.7 Hz, H-20), 3.99 (s, 3H, 5-OCH3), 5.87–5.95 (brs,
NH, 1H), 7.14 (d, 1H, J = 8.3 Hz, H-8), 7.62 (t, 1H,
J = 7.9 Hz, 8.3 Hz, H-6), 7.78 (d, 1H, J = 7.5 Hz, H-7).
13C NMR (75 MHz, CDCl3): d 10.99, 14.05, 22.61, 26.64,
29.15, 29.23, 30.83, 31.74, 45.46, 56.35, 109.90, 115.48,
118.03, 119.09, 135.51, 136.02, 147.17, 159.56, 181.15,
183.15. HR-ESIMS Calcd. for C20H28NO3 (M? ? H):
330.2064. Found: 330.2077.
(E)-5-Methoxy-2-methyl-3-(octadec-9-enylamino)naph-
thalene-1,4-dione (3j): red color liquid. IR(KBr)mmax
:
1
3460, 1643 cm-1. H NMR (300 MHz, CDCl3): d 0.88 (t,
3H, J = 6.2 Hz, 6.7 Hz, 190-CH3), 1.22–1.36 (m, 22H,
H-40–80, H-130–180), 1.55–1.65 (m, 3H, H-30,120),
1.94–2.04 (m, 3H, H-90,120), 2.21 (s, 3H, 2-CH3), 3.53 (q,
2H, J = 6.7 Hz, H-20), 4.00 (s, 3H, 5-OCH3), 5.31–5.39
(m, 2H, H-100,110), 5.87–5.95 (brs, NH, 1H), 7.14 (d, 1H,
J = 8.3 Hz, H-8), 7.62 (t, 1H, J = 8.1 Hz, H-6), 7.78 (d,
1H, 7.7 Hz, H-7). 13C NMR (75 MHz, CDCl3): d 10.99,
14.09, 22.67, 26.65, 27.16, 27.20, 29.18, 29.30, 29.38,
29.50, 29.69, 29.75, 30.83, 31.89, 45.46, 56.35, 109.90,
115.48, 117.99, 119.10, 129.74, 129.98, 135.52, 136.02,
147.16, 159.57, 181.15, 183.15. HR-ESIMS Calcd. for
C30H46NO3 (M? ? H): 468.3472. Found: 468.3492.
3-(Allylamino)-5-methoxy-2-methylnaphthalene-1,4-dione
5-Methoxy-2-methyl-3-(nonylamino)naphthalene-1,4-dione
(3f): mp: 78°C. IR(KBr)mmax: 3458, 2923, 2856, 1663 cm-1. 1H
NMR (300 MHz, CDCl3): d 0.88 (t, 3H, J = 6.2 Hz, 6.7 Hz,
100-CH3), 1.20–1.44 (m, 12H, H-40 and 90), 1.55–1.67 (m, 2H,
H-30), 2.21 (s, 3H, 2-CH3), 3.53 (q, 2H, J = 6.6 Hz, H-20), 3.99
(s, 3H, 5-OCH3), 5.87–5.95 (brs, NH, 1H), 7.14 (d, 1H,
J = 8.3 Hz, H-8), 7.62 (t, 1H, J = 7.9 Hz, 8.1 Hz, H-6), 7.78
(d, 1H, J = 7.5 Hz, H-7). 13C NMR (75 MHz, CDCl3): d
10.94, 14.04, 22.58, 26.59, 29.15, 29.23, 29.39, 30.76, 31.76,
45.38, 56.27, 109.75, 115.38, 117.85, 119.00, 135.46, 135.91,
147.05, 159.46, 181.04, 183.04. HR-ESIMS Calcd. for
C21H29NO3(M? ? H): 344.2220. Found: 344.2226.
3-(Decylamino)-5-methoxy-2-methylnaphthalene-1,4-dione
(3g): mp: 78°C. IR(KBr)mmax: 3451, 2923, 2853, 1663 cm-1
.
(3k): mp: 93°C. IR(KBr)mmax: 3454, 2924, 1615, 1577 cm-1
.
1H NMR (300 MHz, CDCl3): d 0.88 (t, 3H, J = 6.2 Hz,
1H NMR (300 MHz, CDCl3): d 2.18 (s, 3H, 2-CH3), 3.99 (s,
6.7 Hz, 110-CH3), 1.18–1.45 (m, 14H, H-40–100), 1.55–1.69 (m,
3H, 5-OCH3), 4.11–4.18 (m, 2H, H-20), 5.22–5.30 (m, 2H,
123

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Med Chem Res (2012) 21:578–583
H-40), 5.86–5.90 (m, 1H, H-30), 6.00–6.07 (brs, NH, 1H),
7.14 (d, 1H, J = 8.3 Hz, H-8), 7.61 (t, 1H, J = 7.9 Hz,
8.3 Hz, H-6), 7.76 (d, 1H, J = 7.5 Hz, H-7). 13C NMR
(75 MHz, CDCl3): d 10.65, 47.21, 56.24, 110.57, 115.55,
116.64, 117.81, 118.96, 134.61, 135.42, 135.65, 146.85,
159.46, 180.80, 183.15. HR-ESIMS Calcd. for C15H16NO3
(M? ? H): 258.1125. Found: 258.1108.
J = 7.5 Hz, H-7). 13C NMR (75 MHz, CDCl3): d 10.93,
48.67, 56.39, 111.67, 115.84, 119.19, 125.85, 125.90,
127.12, 127.48, 128.05, 135.59, 135.69, 142.92, 146.69,
159.67, 180.85, 183.44. HR-ESIMS Calcd. for C20H17F3NO3
(M? ? H): 376.1155. Found: 376.1164.
Bioassay
3-(Benzylamino)-5-methoxy-2-methylnaphthalene-1,4-
dione (3l): mp: 92°C. IR(KBr)mmax: 3432, 2924, 2857,
Antifeedant activity of the compounds was assessed on the
larvae of tobacco caterpillar (S. litura) and castor semilooper
(A. janata). The experiments were conducted according to the
classical no-choice leaf-disk bioassay described earlier by
Akhtar and Isman (2004). The castor semilooper, A. janata
(L.) and the tobacco cutworm, S. litura (Fab.) were reared on
fresh castor leaves (Ricinus communis (L.)) grown in the
laboratory at 28 2°C, relative humidity 65 5, and 16:8
light:dark photo period. To study the antifeedant activity of
thetestcompounds, asmallcirculardiskof5-cmdiameterwas
cut from fresh castor leaves. The leaf disks were treated on
their upper surface with individual concentrations of the
compounds, and one leaf disk each was transferred to each
Petri plate of 15-cm diameter containing moist filter paper.
Control leaf disks were treated with the same volume of the
solvent only.
1
2306, 1661 cm-1. H NMR (300 MHz, CDCl3): d 2.20
(s, 3H, 2-CH3), 4.00 (s, 3H, 5-OCH3), 4.73 (d, 2H,
J = 5.4 Hz, H-20), 6.17–6.23 (brs, NH, 1H), 7.16 (d, 1H,
J = 8.4 Hz, H-8), 7.26–7.36 (m, 5H, H-100, Ph), 7.63 (t,
1H, J = 7.9 Hz, 8.1 Hz, H-6), 7.79 (d, 1H, J = 7.5 Hz,
H-7). 13C NMR (75 MHz, CDCl3): d 10.99, 49.33, 56.35,
110.96, 115.65, 119.11, 127.04, 127.72, 128.57, 128.76,
128.90, 135.56, 135.77, 146.97, 159.59, 180.97, 183.92.
HR-ESIMS Calcd. for C19H18NO3(M? ? H): 308.1281.
Found: 308.1287.
3-(4-Fluorobenzylamino)-5-methoxy-2-methylnaphtha-
lene-1,4-dione (3m): mp: 100°C. IR(KBr)mmax: 3432.0,
1
2923.9, 2370.9, 1664 cm-1. H NMR (300 MHz, CDCl3): d
2.19 (s, 3H, 2-CH3), 4.00 (s, 3H, 5-OCH3), 4.69 (s, 2H, H-20),
6.07–6.17 (brs, NH, 1H), 7.01–7.08 (m, 2H, H-200, H-600), 7.17
(d, 1H, J = 8.3 Hz, H-8), 7.24–7.29 (m, 2H, H-300, H-500), 7.64
(t, 1H, J = 7.7 Hz, 8.3 Hz, H-6), 7.78 (d, 1H, J = 7.5 Hz,
H-7). 13C NMR (75 MHz, CDCl3): d 11.02, 48.72, 56.38,
111.32, 115.68, 115.76, 115.97, 117.98, 119.17, 128.74,
128.85, 135.61, 135.74, 146.87, 159.65, 180.94, 183.41. HR-
ESIMS Calcd. for C19H16FNO4 (M? ? H): 326.1207. Found:
326.1247.
In each Petri dish, prestarved healthy 3rd instar larvae of
A. janata and S. litura were introduced for assessing their
feeding activity. Progress of the consumption of the leaf
area was measured at 6, 12, and 24 h in both treated and
control leaf disks. Areas of control and treated leaf disks
consumed were measured after 6 h using AM-300 leaf area
meter (ADC, Bioscientific Limited, England, UK). The
antifeedant index was then calculated as (C - T)/
(C ? T) 9 100, where C is consumption of control disks,
and T is consumption of treated disks (Isman et al., 1990).
For each concentration, 10 experimental sets were assayed.
Each test was replicated three times. The mean of the 10 sets
were taken for each compound, and the percentage of anti-
feedant activity with standard deviation was calculated.
5-Methoxy-3-(4-methoxybenzylamino)-2-methylnaph-
thalene-1,4-dione (3n): red color liquid. IR(KBr)mmax
:
3424, 2924, 2858, 1630 cm-1 1H NMR (300 MHz,
.
CDCl3): d 2.21 (s, 3H, 2-CH3), 3.81 (s, 3H, 400-OCH3),
3.99 (s, 3H, 5-OCH3), 4.66 (s, 2H, H-20), 6.03–6.19 (brs,
NH, 1H), 6.88 (d, 2H, J = 8.6 Hz, H-200, H-600), 7.15 (d,
1H, J = 8.3 Hz, H-8), 7.21 (d, 2H, J = 8.4 Hz, H-300,
H-500), 7.62 (t, 1H, J = 7.7 Hz, 8.3 Hz, H-6), 7.78 (d,
1H, J = 7.5 Hz, H-7). 13C NMR (75 MHz, CDCl3): d
11.04, 48.96, 55.27, 56.33, 110.81, 114.26, 115.89,
115.61, 119.08, 123.93, 124.42, 128.47, 135.53, 147.01,
159.14, 159.55, 180.97, 183.33. HR-ESIMS Calcd. for
C20H20NO4(M? ? H): 338.1387. Found: 338.1389.
5-Methoxy-2-methyl-3-(4-(trifluoromethyl)benzylamino)
naphthalene-1,4-dione (3o): mp: 104°C. IR(KBr)mmax: 3426,
Data analysis
Antifeedant indices were calculated using five different
concentrations of each compound, and data were subjected
to probit analysis (Finney, 1971) to determine ED rep-
50
1
2929, 2299, 1663 cm-1. H NMR (300 MHz, CDCl3): d
resenting the concentrations that caused 50% feeding
deterrence along with the 95% fiducial limits.
2.15 (s, 3H, 2-CH3), 4.01 (s, 3H, 5-OCH3), 4.79 (s, 2H,
J = 6.4 Hz, H-20), 6.22–6.30 (brs, NH, 1H), 7.18 (d, 1H,
J = 8.3 Hz, H-8), 7.41 (d, 2H, J = 7.7 Hz, H-200, H-600),
7.59–7.66 (m, 3H, H-6, H-300, H-500), 7.79 (d, 1H,
Acknowledgments The authors gratefully acknowledge the keen
interest evinced by Dr. J. S. Yadav, Director, IICT, Hyderabad, India.
GS and RRR thank the CSIR, New Delhi for the financial support.
123

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583
naturally occurring chitin synthetase inhibitor. Agric Biol Chem
47:911–913
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