YANG ET AL.
5
concentration (LC50) values of some of the target com-
pounds were also evaluated and listed in Tables 2. As
shown in Table 2, compounds E12 and E26 displayed
excellent insecticidal activities against P. xylostella, with
the LC50 values of 6.4 and 4.6 μg/mL, respectively,
which were even better than those of chlorpyrifos
(7.7 μg/mL), beta‐cypermethrin (12.8 μg/mL), and
azadirachtin (10.2 μg/mL). These results indicated that
isoxazole derivatives containing bisamide moiety could
be developed as novel and promising insecticides.
Based on the insecticidal activities of the target com-
pounds against P. xylostella, the preliminary structure‐
activity relationship (SAR) showed that the type and
position of the substituent group R had an important
effect on the insecticidal activity of the target com-
pounds against P. xylostella. First, compared with the
same substituent on the R2 substituent group, with the
presence of electron‐drawing groups (─Cl, ─F) at the
R1 substituent group on phenyl, the corresponding com-
pounds presented better bioactivity against P. xylostella
(E8 > E1, E13 > E1, and E9 > E2). Second, compared
with the same substituent on the R2 substituent group,
with the presence of ─Cl at the R1 substituent group
on phenyl, the insecticidal activities against P. xylostella
of the corresponding compounds with the ─Cl substitu-
ent group at 4‐position were higher than those of at 5‐
position in the order of E13 > E8 and E14 > E9. Third,
compared with the same substituent on the R2 substitu-
ent group, with the presence of ─F at the R1 substituent
group on phenyl, the insecticidal activities against
P. xylostella of the corresponding compounds with the
─F substituent group at 5‐position were higher than
those of at 4‐position in the order of E27 > E20 and
E31 > E23.
4 | CONCLUSIONS
In conclusion, a total of 31 novel isoxazole derivatives
containing bisamide moiety were designed and synthe-
sized. Insecticidal bioassays indicated that some of the
target compounds exhibited excellent insecticidal activity
against P. xylostella. Especially, compound E26 exhibited
the best insecticidal activity against P. xylostella, with a
LC50 value of 4.6 μg/mL, which was superior to those of
chlorpyrifos (7.7 μg/mL), beta‐cypermethrin (12.8 μg/
mL), and azadirachtin (10.2 μg/mL). The results provided
a practical tool for guiding the design and synthesis of
novel and more potent isoxazole derivatives containing
bisamide moiety.
ACKNOWLEDGMENTS
This research was funded by the National Natural Science
Foundation of China (grant 21466031) and Youth Science
and Technology Talent Growth Program of Guizhou
Province's Department of Education (grant Qian Jiaohe
KY [2018] 350).
CONFLICT OF INTERESTS
The authors declare no conflict of interest.
ORCID
REFERENCES AND NOTES
[1] N. S. Talekar, A. M. Shelton, Annu Rev Entomol 1993, 38, 275.
[2] N. M. Endersby, S. W. Mckechnie, P. M. Ridland, A. R. Weeks,
Mol Ecol 2006, 15, 107.
[3] B. E. Tabashnik, Y. B. Liu, T. Malvar, D. G. Heckel, L. Masson,
V. Ballester, F. Granero, J. L. Ménsua, J. Ferré, PNAS 1997, 94,
12780.
TABLE 2 The LC50 values of the testing compounds against
Plutella xylostella
[4] J. Z. Zhao, Y. X. Li, H. L. Collins, L. Gusukuma‐Minuto, R. F.
L. Mau, G. D. Thompson, A. M. Shelton, J Econ Entomol
2002, 95, 430.
Compounds
y = ax + b
r
LC50 (μg/mL)
E12
y = 1.56x + 3.74 0.99
6.4 1.4
[5] A. H. Sayye, D. J. Wright, Pest Manag Sci 2006, 62, 1045.
[6] J. Hu, P. Liang, X. Shi, X. Gao, J Insect Sci 2008, 8, 1.
E13
y = 1.12x + 3.36 0.99 29.0 1.9
y = 1.41x + 2.60 0.98 48.4 2.2
y = 1.30x + 3.13 0.99 27.6 2.0
E20
[7] A. Seo, M. Tohnishi, H. Nakao, T. Furuya, H. Kodama, K.
Tsubata, S. Fujioka, H. Kodama, T. Nishimatsu, T. Hirooka,
Flubendiamide, a new insecticide characterized by its novel
chemistry and biology. In: H. Ohkawa, H. Miyagawa, P. W.
Lee (eds) Pesticide chemistry: crop protection, public health, envi-
ronmental safety, Wiley‐VCH, Weinheim, Germany 2007, 127.
E23
E26
y = 1.33x + 4.11 0.99
4.6 1.2
E27
y = 1.67x + 2.65 0.96 25.6 2.7
y = 1.37x + 3.12 0.98 23.8 2.5
E31
Chlorpyrifos
y = 1.07x + 4.05 0.98
7.7 1.5
[8] G. P. Lahm, T. M. Stevenson, T. P. Selby, J. H. Freudenberger,
D. Cordova, L. Flexner, C. A. Bellin, C. M. Dubas, B. K. Smith,
K. A. Hughes, J. G. Hollingshaus, C. E. Clark, E. A. Benner,
Bioorg Med Chem Lett 2007, 17, 6274.
beta‐Cypermethrin y = 1.32x + 3.53 0.98 12.8 2.3
Azadirachtin y = 1.06x + 3.93 0.96 10.2 3.1