Structural Optimization of the Natural Product: Discovery of Almazoles C–D and Their Derivatives as Novel Antiviral and Anti-phytopathogenic Fungus Agents

Abstract

Plant diseases seriously affect the growth of crops and the quality and yield of agricultural products. The search for plant-derived pesticide candidates based on natural products is a hot topic of current research. Marine natural products almazoles C−D were efficiently prepared and selected as the lead compounds in this work. Two series of almazole derivatives were designed and synthesized, and their antiviral and fungicidal activities were systematically evaluated. The results of anti-tobacco mosaic virus (anti-TMV) activity showed that almazoles C−D and their derivatives had good anti-TMV activities. Compounds 6,15, 16a, 16b, 16g, 16l, 16n, 20a, 20d, 20i, and 20n exhibited better anti-TMV activities than the commercial antiviral agent ribavirin. Anti-TMV mechanism studies showed that compound 16b could induce the polymerization of 20S CP (coat protein, CP), thereby affecting the assembly of TMV virus particles. Molecular docking results showed that compounds 15, 16b, and 20n could combine with amino acid residues through hydrogen bonds to achieve an excellent anti-TMV effect. In addition, most of the almazole derivatives were found to have broad-spectrum fungicidal activities against eight kinds of plant pathogens (Fusarium oxysporum f. sp. cucumeris, Cercospora arachidicola Hori, Physalospora piricola, Rhizoctonia cerealis, Alternaria solani, Pyricularia grisea, Phytophthora capsici, and Sclerotinia sclerotiorum). This study provides an important evidence for the research and development of almazole alkaloids containing indole and oxazole structural groups as novel agrochemicals.

Design, Synthesis, Structure–Activity Relationship, and Three-Dimensional Quantitative Structure–Activity Relationship of Fusarium Acid Derivatives and Analogues as Potential Fungicides

“…13 However, most unmodified NPs have the characteristic of poor solubility or instability, which makes them unsuitable for direct use in drugs. 14 Therefore, NPs usually undergo structural modifications before their application. 15−17 For pest control, neon-icotinoids and pyrethrin are modified products obtained from the tobacco extract nicotine and Pyrethrum (Chrysanthemum cinerariaefolium, Asteraceae family), 18,19 respectively (Figure 1).…”

“…Natural products (NPs) are the pesticide treasure trove bestowed by nature. − Recently, owing to their novel chemical structures, diverse biological properties, and unusual mechanisms of action, NPs have become important for designing and developing drugs . However, most unmodified NPs have the characteristic of poor solubility or instability, which makes them unsuitable for direct use in drugs . Therefore, NPs usually undergo structural modifications before their application. − For pest control, neonicotinoids and pyrethrin are modified products obtained from the tobacco extract nicotine and Pyrethrum (Chrysanthemum cinerariaefolium, Asteraceae family), , respectively (Figure ).…”

“…In recent years, most studies on FA have focused on the mechanism of its occurrence and the process of infecting crops; however, the prospect of FA as an excellent agricultural fungicide with considerable development potential has been ignored. In our previous study, FA demonstrated a good broad-spectrum inhibitory effect on the growth of 14 derivatives with effective antifungal activities have been independently designed and synthesized on the basis of the different pharmacological activities of FA. The molecular structure of these compounds is more novel than that of conventional commercial fungicides; moreover, some compounds have not been reported.…”

Sequential annulation and isomerisation reaction of 3-acylmethylidene oxindoles with Huisgen zwitterions and synthesis of 5-(3-oxindolyl)oxazoles

“…1 As a combination of indole and other heterocycles, the 5-(3-indolyl)oxazole natural alkaloids have gained considerable attention due to the biological importance of both indole and oxazole cores. 2–6 Examples include the pimprinine family alkaloids, 2 almazole D, 3 breitfussin A 4 (Fig. 1) and others, 5 which exhibit a wide spectrum of bioactivities such as antiviral, anticonvulsant, antiepileptic, anticancer, and antibacterial activities.…”

“…1) and others, 5 which exhibit a wide spectrum of bioactivities such as antiviral, anticonvulsant, antiepileptic, anticancer, and antibacterial activities. 6 Given their biological significance and structural diversity, the assembly of 5-(3-indolyl)oxazoles has accordingly attracted substantial scientific interest as organic synthesis subjects. 7 Early methods to access these scaffolds mainly relied on intramolecular Robinson–Gabriel cyclizations 2 a ,8 or intermolecular cycloadditions 2 b ,9 of 3-acylindoles for the construction of oxazole rings.…”