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. 2019 Oct 19;24(20):3766.
doi: 10.3390/molecules24203766.

Design, Synthesis, and Bioactivity Evaluation of Novel Isoxazole-Amide Derivatives Containing an Acylhydrazone Moiety as New Active Antiviral Agents

Zai-Bo Yang  1 , Pei Li  2   3 , Yin-Ju He  4
Affiliations

Design, Synthesis, and Bioactivity Evaluation of Novel Isoxazole-Amide Derivatives Containing an Acylhydrazone Moiety as New Active Antiviral Agents

Zai-Bo Yang et al. Molecules. .

Abstract

As a continuation of our efforts to discover and develop "me-better" active molecules, in this study, a series of novel isoxazole-amide derivatives containing an acylhydrazone moiety were synthesized and evaluated for their antiviral activities against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). Antiviral bioassays indicated that some of the target compounds exhibited better in vivo antiviral activities against TMV and CMV than those of Ningnanmycin (NNM). Especially, the compound 7t exhibited the best curative, protection, and inactivation activities against TMV and CMV which were superior to those of NNM. Meanwhile, our present work also revealed that compound 7t could enhance the defense-related enzyme activity and increase the chlorophyll content in tobacco leaves to induce resistance and enhance plant tolerance to TMV infection.

Keywords: acylhydrazone; antiviral activity; isoxazole-amide; synthesis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Design route of the target compounds.
Scheme 1
Scheme 1
Synthetic route of the target compounds 7a–7v.
Figure 2
Figure 2
The preliminary in vivo antiviral activities against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) of the target compounds 7a–7v at 500 mg/L. (A) Curative activity against TMV, (B) Protection activity against TMV, (C) Inactivation activity against TMV, (D) Curative activity against CMV, (E) Protection activity against CMV, (F) Inactivation activity against CMV. * p < 0.05, ** p < 0.01. Vertical bars refer to mean ± SD (n = 3).
Figure 3
Figure 3
The EC50 values of the target compounds 7a–7v against TMV and CMV in vivo. (A) Curative activity against TMV, (B) Protection activity against TMV, (C) Inactivation activity against TMV, (D) Curative activity against CMV, (E) Protection activity against CMV, (F) Inactivation activity against CMV. * p < 0.05, ** p < 0.01. Vertical bars refer to mean ± SD (n = 3).
Figure 4
Figure 4
Effects of compound 7t on chlorophyll a (Ca) (A), chlorophyll b (Cb) (B), and total chlorophyll content (Ct) (C) contents in tobacco leaves. Vertical bars refer to mean ± SD (n = 3). CK, negative control.
Figure 5
Figure 5
Effects of compound 7t on superoxide dismutase (SOD) (A), peroxidase (POD) (B), catalase (CAT) (C), and phenylalanine ammonia lyase (PAL) (D) activity in tobacco leaves. Vertical bars refer to mean ± SD (n = 3). CK, negative control.
See this image and copyright information in PMC

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