posted on 2023-12-04, 11:00authored byLei Wang, Wenqi Fan, Li Cui, Na Yang, Xiao Zhang, Shujing Yu, Yonghong Li, Baolei Wang
On the basis of the structures of natural methylxanthines
and chalcone,
a series of novel chalcone analogues containing a methylxanthine moiety, Ia–Ig, and their N-acyl
pyrazoline derivatives IIa–IIz and IIaa–IIaf were synthesized and identified
through melting points, 1H NMR, 13C NMR, and
HRMS. The single crystal of compound IId was obtained,
which further illustrated the structural characteristics of the methylxanthine-acylpyrazoline
compounds. The biological tests showed that some of them displayed
favorable insecticidal activities toward Plutella xylostella L. and were superior to the natural methylxanthine compound caffeine
while being comparable with the insecticide triflumuron (e.g., compound Ic: LC50 = 16.8508 mg/L, IIf: LC50 = 1.5721 mg/L, against P. xylostella). Of these compounds, Ic, IIf, and IIu could serve as novel insecticidal leading structures for
further study. Some of the compounds showed good fungicidal activities
(e.g., compound Ig: EC50 = 14.74 μg/mL,
against Rhizoctonia cerealis; IIf: EC50 = 7.06 μg/mL, against Physalospora piricola; IIac: EC50 = 5.37 and 8.19 μg/mL, against Phytophthora
capsici and Sclerotinia sclerotiorum, respectively); Ic, Ig, IIa, IIf, IIr, IIs, IIv, IIac, and IIaf could be novel fungicidal
leading compounds for further exploration. Furthermore, most of the
tested compounds exhibited apparent herbicidal activities against Brassica campestris at a concentration of 100 μg/mL;
among others, compound IIa was the best one both toward Brassica campestris and Echinochloa
crusgalli and deserves further investigation. The
structure–activity relationships of these compounds were also
summarized and discussed in detail. The contrast experiment results
of compounds C-1 and C-2 showed a positive
effect on the biological activity enhancement from the combination
of the methylxanthine moiety with the N-dichloroacetyl
phenylpyrazoline skeleton. In addition, two 3D-QSAR models with predictive
capability were constructed based on the insecticidal and fungicidal
activities to afford deep insight into the bioactivity profiles of
these compounds. This research provides useful guidance and reference
for the discovery and development of novel xanthine natural product-based
pesticides.