Anti-Tobacco Mosaic Virus Quassinoids from Ailanthus altissima (Mill.) Swingle

Abstract

Quassinoids are bitter constituents characteristic of the family Simaroubaceae. A total of 18 C quassinoids, including nine new quassinoid glycosides, named chuglycosides A-I (1-6 and 8-10), were identified from the samara of Ailanthus altissima (Mill.) Swingle. All of the quassinoids showed potent anti-tobacco mosaic virus (TMV) activity. A preliminary structure-anti-TMV activity relationship of quassinoids was discussed. The effects of three quassinoids, including chaparrinone (12), glaucarubinone (15), and ailanthone (16), on the accumulation of TMV coat protein (CP) were studied by western blot analysis. Ailanthone (16) was further investigated for its influence on TMV spread in the Nicotiana benthamiana plant.

Two Novel Quassinoid Glycosides with Antiviral Activity from the Samara of Ailanthus altissima

“…21-3.08 (2H, overlap, H-3 and H- Figure S4) and distortionless enhancement by polarization transfer (DEPT) ( Figure S5) NMR spectra revealed that compound 1 has 26 carbons including two carbonyl (δ C 207.7 and 169.1), two olefinic carbons (δ C 134.6 and 124.2), one hemiketal carbon (δ C 106.9), six saccharide-type carbons (δ C 105.2, 76.7, 76.3, 74.2, 70.0 and 61.1), as well as three methyl, three methylene, seven methine, and two quaternary carbons. The above 1 H and 13 C-NMR data were similar to those of the quassinoid glycosides isolated from the same plant materials, as reported previously in our paper [13]. Specifically, a keto group was attached at C-12 position, as indicated by the observed HMBC correlations ( Figure 2 Compound 1 was isolated as a colorless crystal, and its molecular formula was established as C26H36O12 by high resolution ionization mass spectroscopy (HRESIMS) (m/z 564.2175 [M + Na + H] + , calcd for C26H37O12Na 564.2177) ( Figure S1).…”

“…By the year 2004, more than 200 natural quassinoids obtained from 34 species in 14 genera were reported, and the structural characteristics of 190 quassinoids were reported between the year 2004 and 2018 [27,28]. Thus far, more than 50 quassinoids have been isolated from A. altissima, most of which belong to the C 20 class bearing a δ-lactone moiety [13,26]. Pharmacological and clinical investigations have revealed that C 20 quassinoids from Ailanthus genus plant are very promising for their medical use, such as antitumor, antimalarial, antiviral, antiparasitic properties etc.…”

“…The generated name chuglycoside arises from 'chu', the Chinese phonetic alphabets of one of the variant names of A. altissima, which is commonly used in the classics of traditional Chinese medicine. The quassinoids previously obtained from the samara of A. altissima can generally be classified as the C-6 or C-15 substituted derivatives of chaparrione and ailanthone, as well as their monoglycosides [13]. Ailanthone is the best known bioactive secondary metabolite isolated from A. altissima, which displays multiple pharmacological properties, in particular significant antitumor effects against a variety of cancer cell lines in vitro [29,30].…”

“…Phytochemical investigations have reported the characterization of quassinoids, β-carboline alkaloids, triterpenoids, coumarins, phenylpropionamides, piperidine, and phenolic derivatives [7][8][9][10][11][12], etc. We have initiated a phytochemistry study on the samara of A. altissima, and previously we have reported the identification of 58 natural products of diverse structures such as quassinoids, coumarins, flavonoids, phenylpropanoids, phenylpropionamides, piperidine and phenolic derivatives, among which were a series of novel compounds including nine quassinoid glycosides, two phenylpropionamides, one piperidine, one terpenylated coumarin and two phenolic derivatives [5,7,13]. In this paper, we report the purification and identification of another two novel quassinoid glycosides, named chuglycosides J (1) and K (2), which were isolated from the A. altissima samara during our ongoing studies, together with fourteen known lignan and neolignans including tetrahydro-2-(4-hydroxy-3-methoxyphenyl)-4-[(4-hydroxyphenyl) methyl]-3-furanmethanol (3) [14], (+)-lariciresinol (4) [15], (+)-(1R,2S,5R,6S)-2,6-di(4 -hydroxyphenyl)-3,7-dioxabicyclo [3.3.0]octane (5) [16], (+)-pinoresinol (6) [17], (+)-isolariciresinol (7) [18], (+)-isolariciresinol 3α-O-β-glucopyranoside (8) [19], burselignan (9) [18], densispicoside (10) [20], secoisolariciresinol (11) [15], dehydroconiferyl alcohol (12) [21], curcasinlignan B (13) [22], erythro-guaiacylglycerol-β-O-4 -coniferyl ether (14) [23], 7R,8R-threo-4,7,9,9 -tetrahydroxy-3,3 -dimethoxy-8-O-4 -neolignan (15) [24], threo-2,3-bis-(4-hydroxy-3-methoxyphenyl)-3-methoxypropanol…”

Anticancer properties and mechanism of action of the quassinoid ailanthone

“…In a large series of 63 quassinoids tested for inhibition of Krebs ascites translation extracts, AIT appeared among the most active compounds but slightly less active than the analogous alkaloids bruceantin and brusatol (Fukamiya et al, 2005). In addition, AIT displays antiviral properties, notably against the tobacco mosaic virus (TMV) (Tan et al, 2018). The drug exhibits antitubercular and antiplasmodial activities (Okunade et al, 2003; Rahman, Fukamiya, Okano, Tagahara, & Lee, 1997).…”