Discovery of Phytoalexin Camalexin and Its Derivatives as Novel Antiviral and Antiphytopathogenic-Fungus Agents

Abstract

In response to the invasion of plant viruses and pathogenic fungi, higher plants produce defensive allelochemicals. Finding candidate varieties of botanical pesticides based on allelochemicals is one of the important ways to create efficient and green pesticides. Here, a series of camalexin derivatives based on a phytoalexin camalexin scaffold were designed, synthesized, and assessed for their antiviral and fungicidal activities systematically. Most of these camalexin derivatives exhibited better antiviral activities against tobacco mosaic virus (TMV) than the control antiviral agent ribavirin. Under the same test conditions, the anti-TMV activities of compounds 3d, 5a, 5d, and 10f−10h were found to be equivalent to or better than that of ningnanmycin, an agricultural cytosine nucleoside antibiotic with excellent protective effect. The antiviral mechanism research showed that compound 5a could cause 20S CP disk fusion and disintegration, thus affecting the assembly of virus particles. The results of molecular docking indicate that there were obvious hydrogen bonds between compounds 3d, 5a, and 10f and TMV CP. The binding constants of compounds 5a and 10f to TMV CP were also calculated using fluorescence titration. These camalexin derivatives also presented broad spectrum fungicidal activities, especially for Rhizoctonia solani and Physalospora piricola. In this work, the design, synthesis, structure optimization, and mode of action of camalexin derivatives were carried out progressively. This work provides a reference for using defensive chemical compounds as novel pesticide lead compounds.

Plant Viral Coat Proteins as Biochemical Targets for Antiviral Compounds

“…Further, various novel phosphorylated penta-1,4-dien-3-one derivatives (e.g., 3h , EC 50 104.2 μg/mL, and 3j , EC 50 290.0 μg/mL) and dithioacetal derivatives (e.g., Y21 , EC 50 329.5 ± 1.5 μg/mL) exhibited good antiviral activity against TMV and inhibited TMV activity by binding to TMV CP. − In 2021, Guo et al designed and synthesized novel acylurea derivatives (e.g., 7x , EC 50 211.8 μg/mL) with good antiviral activity, which could target TMV CP and inhibit TMV self-assembly thereby suppressing viral infestation . In 2022, Liao et al synthesized a series of camalexin derivatives, screened them against TMV CP, and found that compound 5a caused fusion and disassembly of 20S CP discs, thus affecting the assembly of viral particles . In the same year, Dai et al synthesized a ferulic acid derivative ( D3 , EC 50 38.1 μg/mL) containing β-amino alcohols.…”

“…60−62 In 2021, Guo et al designed and synthesized novel acylurea derivatives (e.g., 7x, EC 50 211.8 μg/mL) with good antiviral activity, which could target TMV CP and inhibit TMV self-assembly thereby suppressing viral infestation 63. In 2022, Liao et al synthesized a series of camalexin derivatives, screened them against TMV CP, and found that compound 5a caused fusion and disassembly of 20S CP discs, thus affecting the assembly of viral particles 64. In the same year, Dai et al synthesized a ferulic acid derivative (D3, EC 50 38.1 μg/mL) containing βamino alcohols.…”

Splicing Indoles and 4,5-Dihydro-1H-pyrazoline Structure Gave Birth to Novel Antiviral Agents: Design, Synthesis, and Mechanism Study

“…Indole and its derivatives have received copious attention for their physicochemical and pharmacological properties. Meanwhile, indole derivatives have broad-spectrum biological activities, such as antibacterial, − anti-inflammatory, − and antiviral. − Therefore, commercial products with an indole backbone can be continually searched for in research and development in pesticides and pharmaceuticals. Recent studies have shown that the antiviral mechanism of most indole-containing compounds increases the plant body’s autoimmunity to fulfill disease rebellion. − As a promising moiety in this category, 4,5-dihydro-1 H -pyrazoline exhibits diverse activities, which have led to the development of numerous commercially available drugs for application to insecticides, − antivirals, − herbicides, − and fungicides. − Thiourea is likewise an active structure, and its most well-known feature is its ability to serve as a hydrogen bond former, which helps strengthen the molecule’s binding to the probable target.…”

“…In addition, we scrutinized the effect of the reaction conditions on the yield of the target chemical. The results indicated that when the reaction period is less than 2 h, the reaction system produces almost no target chemical; when the reaction feedstock KOH and aminothiourea equivalents are less than 1.5 and 1.5, a substantial increase in reaction time is necessary to increase the target compound yield; the best yields of the target compounds were produced when the reaction materials C1, KOH, and aminothiourea equivalents were correspondingly 1.0, 3.0, and 3.0 for more than 8 h. Then, 1 H, 13 C, and 19 F NMRs and HRMS were used to elucidate the chemical structures of compounds D1−D40 (see Supporting Information).…”

Design, Synthesis, and Biological Evaluation of Novel Osthole-Based Isoxazoline Derivatives as Insecticide Candidates

“…Natural products (NPs) not only possess diverse structures and pharmacological properties but also have unique effects, easy degradation, or good compatibility with the environment. − They have been used by humans as dyes, food additives, drugs, and pesticides for thousands of years. In recent years, the development of NP-based pesticides has become a hot topic. − Osthole ( 1 , Figure ) is a naturally occurring coumarin compound found mainly in Apiaceae (Umbelliferae) and Brassicaceae plants . It is highly abundant in the ripe fruit of Cnidium monnieri (L.) Cusson, which is commonly used as a traditional Chinese medicine .…”