Trypanocidal Constituents in Plants 6. Minor Withanolides from the Aerial Parts of Physalis angulata

Abstract

Physalis angulata L. (Solanaceae) is indigenous in tropicalAmerica and was naturalized in Japan in the Edo era. It is an annual small herb and has been traditionally utilized for antipyretic purposes in Japan.2) In the previous paper in this series, 3) we described the investigation of constituents in P. angulata based on the plant's trypanocidal activity against epimastigotes of Trypanosoma cruzi, the etiologic agent for Chagas' disease (American trypanosomiasis). Ten withanolides (1-10), including four new ones, were isolated from the active fraction. Trypanocidal activity of these withanolides against trypomastigotes, an infectious form of T. cruzi, was also estimated, as well as cytotoxic activity against human uterine carcinoma (HeLa) cells in vitro to examine the possibility of chemotherapeutic utility.Continuous study of the same plants resulted in the isolation of three new withanolides (11-13), designated physagulin L, M and N, respectively, together with known withanolide, physagulin D 4) (14) and flavonol glycoside, quercetin 3-O-rhamnosyl-(1→6)-galactoside (15).5) The structures of the known compounds were identified from their spectral data and confirmed by comparison with those published in the literature. In this paper we describe the structural elucidation of the three new withanolides and the trypanocidal activity of the isolates.Compound 11 has the molecular formula C 30 H 42 O 10 , one oxygen atom more than physagulin K (10).3) The 1 H-and 13 C-NMR spectra of 11 were similar to those of 10, except for signals in ring E, suggesting the same substitution pattern in rings A-D. In the 1 H-NMR spectrum, one olefinic methyl signal at d 2.04 (br s) and one hydroxymethylene signal at d 4.74 and 4.88 (d each, Jϭ12 Hz) were observed in 11, instead of two olefinic methyl signals in 10. In the 13 C-NMR spectrum of 11, the corresponding signals due to the olefinic methyl and hydroxymethylene groups were observed at d 20.0 and 56.2 accompanied with downfield shifts of C-24 (ϩ4.4 ppm) and C-25 (ϩ5.5 ppm) in comparison with those of 10. Therefore, it was suggested that one of the methyl groups at C-24 or C-25 was replaced with a hydroxymethylene group in 11. The methyl proton signal showed 3-bond connectivity with C-23 as well as C-25, and the hydroxymethylene proton signals with C-26 in the heteronuclear multiple-bond connectivity (HMBC) spectrum. Thus, the structure of 11 was elucidated to be (20R,22R)-15a-acetoxy5a ,6b ,14b ,17b ,27-pentahydroxy-1-oxo-witha-2,24-dienolide, and it is called physagulin L.The molecular formula of 12 was determined to be C 30 H 40 O 9 by HR-FAB-MS, one oxygen atom more than withaminimin (8).6) The 1 H-and 13 C-NMR spectra showed characteristic signals for a 1-one-2-ene system, 5a,6b-glycol moiety, and a 14a-hydroxy-15a-acetoxy-16-ene system. In fact, signals due to rings A-D were in good agreement with those of 8. As a part of the side chain, a carbon signal of hy- 1226 Vol. 54, No. 8 Trypanocidal Constituents in Plants 6. 1) Minor Withanolides from the Aerial Parts of Phy...

Withanolides and Related Steroids

“…The latter withanolide was incorrectly named physagulin L, as this name had already been assigned (see below). Physagulin N (106), the methanol addition product of physagulin A, was probably formed during its isolation (57). D 16 -Withanolides with oxygen substituents at C-14 and C-15 have the appropriate functionalities for cleavage of the 13,14-bond, and the occurrence of such withanolides in physalin-rich plants strongly suggests that they are either precursors or shunt products in the biosynthesis of physalins (59).…”

“…Physalin F (450) from Physalis angulata was shown to be moderately active. Abe and coworkers investigated the trypanocidal activity of ten withanolides from P. angulata growing in Japan, against T. cruzi epimastigotes and trypomastigotes (the infectious form of the parasite) (57,66). Physagulins A-C (496-498), H (117) and I (118), and withangulatin A (499) had activity against both forms of T. cruzi similar to their cytotoxicity; activity against trypomastigotes was higher for these withanolides.…”

Plants from Solanaceae family with possible anxiolytic effect reported on 19th century's Brazilian medical journal

“…Phytochemical: seco-steroids (physalins) (Soares et al, 2006;Abe et al, 2006;Kuo et al, 2006;Magalhães et al, 2006a;Magalhães et al, 2006b;Damu et al, 2007), alkaloids (Edeoga et al, 2005), tannins and flavonoids (Edeoga et al, 2005;Wollenweber et al, 2005), the withanolides withangulatin (Lee et al, 2008) and physagulins . Patents that were reported, both in the European Patent Office and the Brazilian National Institute of industrial Property databases, most of which concern inflammatory, allergic, parasitic, infectious or digestive diseases, including extracts from P. angulata (Balbani et al, 2009 (Zakaria et al, 2006); can cause a central nervous system depression which may be correlated with an increased parasympathetic tone (Perez et al, 1998), antioxidant (Al-Fatimi et al, 2007); antipyretic and anticancer agent (Hsieh et al, 2008;Hsu et al, 2009;Yang et al, 2010;Li et al, 2008;Li et al, 2009), mutagenic activity (Almeida et al, 2010).…”

Three new physalins from Physalis alkekengi var. franchetii

“…Neophysalins, are another characteristic structure, and are transformed from physalins through an acid-induced benzilic acid-type rearrangement reaction 8 . , anti-inflammatory 13,14 , immunomodulatory 15 , cytotoxic 16 , and trypanocidal 17,18 effects.…”