Discovery of Pimprinine Alkaloids as Novel Agents against a Plant Virus

Abstract

Plant viral diseases cause tremendous decreases in crop yield and quality. Natural products have always been a valuable source for lead discovery in medicinal and agricultural chemistry. A series of pimprinine alkaloids and their derivatives were prepared and identified by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). The antiviral activities of these alkaloids against tobacco mosaic virus (TMV) were systematically investigated for the first time. Most of the compounds exhibited higher antiviral activities than ribavirin. Compounds 5l, 9h, and 10h, which had similar or higher antiviral activities than ningnanmycin (perhaps the most widely used antiviral agent at present), emerged as new antiviral pilot compounds. This systematic structure–activity-relationship research lays the foundation for simplifying the structure of these alkaloids. The ring-open products, acylhydrazones 9a–9u, were also found to possess good antiviral activities. Moreover, all the synthesized compounds displayed broad-spectrum fungicidal activities. This study provides important information for the research and development of pimprinine alkaloids as novel antiviral agents.

Dimeric Pimprinine Alkaloids From Soil-Derived Streptomyces sp. NEAU-C99

“…Pimprinine is an indole alkaloid, which was first isolated from the filtrates of Streptomyces pimprina cultures in 1963 (Joshi et al, 1963). Members of this family display a range of biological activities, such as antiepileptic (Naik et al, 2001;Roy et al, 2006), platelet-aggregation-inhibitory (Miao et al, 2004), antitumor (Pettit et al, 2002), fungicidal (Zhang et al, 2012), and anti-plant-viral activities (Liu et al, 2019).…”

“…NEAU-C99, isolated from a soil sample collected in Mount Song, Henan province, China, in 2016, indicated distinct UV absorptions compared with the extracts of other strains. As a result, six new pimprinine alkaloids (1-6), along with six known congeners (7-12) including pimprinol C (7) (Raju et al, 2012), pimprinol A (8) (Raju et al, 2012), (5-(1H-indol-3-yl)oxazol-2-yl)methanol (9) (Liu et al, 2019), pimprinine (10) (Noltemeyer et al, 1982), pimprinethine (11) (Pettit et al, 2002), and WS-30581 A (12) (Wei et al, 2014), were isolated from Streptomyces sp. NEAU-C99 (Figure 1).…”

Anti‐TMV activity and mode of action of three alkaloids isolated from Chelidonium majus

“…37 Pimprinine alkaloids and their derivatives displayed good anti-TMV activities similar to or higher than that of ningnanmycin and ribavirin, emerging as new lead compounds for antiviral research. 38 Bruceine-D, a kind of alkaloid extracted from Brucea javanica exhibited significant inhibitory activity against both viral infection and replication. 30 It can be seen that botanical alkaloids are potentially effective antiviral factors with different modes of action.Nowadays, plant immunity induced by botanical compounds is a promising alternative way of biological management of diseases and pests.…”

Taxonomic Characterization, and Secondary Metabolite Analysis of Streptomyces triticiradicis sp. nov.: A Novel Actinomycete with Antifungal Activity

“…Cultural characteristics were determined on the ISP media 1-7 [13], Bennett's agar [16], Czapek's agar [17], and Nutrient agar [18] after 2 weeks at 28 • C. The color of substrate mycelium, aerial mycelium, and diffusible pigment on the different tested media were determined using color chips from the ISCC-NBS color charts [19]. Temperature tolerance for growth was evaluated at 4,10,15,20,25,28,35,37,40, and 45 • C on ISP 3 agar after incubation for 2 weeks. The pH range for growth (pH 3.0-12.0, at intervals of 1.0 pH unit) was tested in GY broth [20] using the buffer system described by Zhao et al [21] and NaCl tolerance (0%-15% (w/v) in 1% intervals) for growth was determined after 2 weeks growth in GY broth at 28 • C with shaking at 250 rpm.…”

“…Therefore, novel 2 of 17 antifungal agents and antagonistic microorganisms are needed to effectively control the fungal diseases of agricultural crops. Natural products and their derivatives, in particular secondary metabolites derived from Streptomyces, have always been valuable sources for lead discovery in medicinal and agricultural chemistry because their novel scaffolds can provide new modes of action [3,4]. Members of the genus Streptomyces species are gram-positive, filamentous, and sporulating actinobacteria containing a number of biosynthetic gene clusters, indicating their potential ability to produce large numbers of secondary metabolites with diverse biological activities [5,6], and they represent the source of 75% of clinically useful antibiotics presently available [7].…”