Antiproliferative Constituents in Plants. 10. Flavones from the Leaves of Lantana montevidensis BRIQ. and Consideration of Structure-Activity Relationship.

Abstract

Lantana camara L. is indigenous to tropical America, and its leaves have been used in folk medicine for the treatment of bronchitis and stomach disorders and as a sudorific, and are also put into baths to treat rheumatism in South America.2) However, this species has been known to be toxic to livestock, which develop hepatotoxicity and photosensitization on ingestion of the leaves.3) There have been many reports on the biological action of this plant and the toxic constituents. Scores of triterpene derivatives have been isolated, [3][4][5][6] and some of them have been reported to exhibit inhibitory activity against Epstein-Barr virus early antigen activation in Raji cells induced by 12-O-tetradecanoyl-phorbol-13-acetate. 7)L. montevidensis BRIQ. is native to Brazil (Montevideo), and the tea and infusion of the dried leaves have been used in folk medicine for the same purposes as L. camara.2) However, to our knowledge there is only one report on the essential oil from the leaves 2) and there is no report on the other constituents.Among several Verbenaceae plants in which we investigated the antiproliferative activity of the MeOH extracts, L. camara and L. montevidensis exhibited higher activity against tumor cell growth. The MeOH extract of the leaves of L. montevidensis showed 50% growth inhibition (GI 50 ) at the concentrations of 8 mg/ml for human gastric adenocarcinoma (MK-1), 3 mg/ml for human uterus carcinoma (HeLa), and 4 mg/ml for murine melanoma (B16F10), which were more potent than the inhibition by the MeOH extract of the leaves of L. camara (12.5 mg/ml for MK-1 and 25 mg/ml for HeLa and B16F10). The inhibitory activity was found to be localized in the nonglycoside fraction that contains several flavonoids. The nonflavonoid fraction exhibited higher activity, however, the flavonoid fraction also showed significant activity. We therefore first investigated the active constituents in the flavonoid fraction. This paper deals with the isolation and identification of the flavone constituents in the leaves of L. montevidensis and their antiproliferative activity. MATERIALS AND METHODS Materials, Reagents, and InstrumentsThe leaves of L. montevidensis were collected in Munakata City, Fukuoka, Japan, in July 2000 and air-dried. 6-Hydroxyluteolin, desmethoxycentaureidin, and jaceosidin were isolated from the herb of Lippia canescens KUNTH. (Verbenaceae), 1) and eupatilin was isolated from the herb of Artemisia ludoviciana NUTT. subsp. mexicana (WILLD. ex SPRENGEL) (Compositae). 8)Pectolinarigenin was obtained by acid hydrolysis of linariin isolated from the herb of Trifolium dubium SIBTH. (Leguminosae) and identification was performed by comparison of the NMR data with those reported. 9) Chrysin, luteolin, baicalein, and 6-and 7-methoxyflavones were purchased from Aldrich Chemical Company (Milwaukee, WI, U.S.A.). Reagents for culture of the tumor cells and for the bioassay were described in a previous paper.10) The instruments used in this study were a Shimadzu Double Beam Spectrometer UV-200S (UV spectra), JE...

Genus Lantana: chemical aspects and biological activities

“…Lantana indica Roxb., a wild perennial shrub, native to India, is regarded both as notorious weed and a popular ornamental garden plant (Kumar et al, 2010). Lantana montevidensis Briq., a shrub native to Brazil and Uruguay, is popularly known as "cambara", and it was introduced to many countries as an ornamental plant (Nagão et al, 2002;Barreto et al, 2010). Lantana achyranthifolia Desf.…”

“…showed antiproliferative activity against human gastric adenocarcinoma (MK-1, GI50 12 µg/mL), human uterine carcinoma (HeLa, 5 µg/ mL), and murine melanoma (B16F10, 5 µg/mL) cells in vitro (Nagão et al, 2002). In the same study, flavones isolated from the flavonoid fraction of this plant, 5,3',4'-trihydroxy-6,7,5'-trimethoxyflavone (95), apigenin (90), cirsiliol (98) and eupafolin (99), showed higher activity against the three tumor cell lines followed by eupatorin (92), 5,6-dihydroxy-7,3',4'-trimethoxyflavone (80), 5,6,4'-trihydroxy-7,3',5'-trimethoxiflavone (96) and 5,6,3'-trihydroxy-7,4'-dimethoxyflavone (81).…”

A new approach for the synthesis of bioactive heteroaryl thiazolidine-2,4-diones

“…Similarly, the reaction of compound 3 with cyanoguanidine under the same reaction conditions yielded the 5-(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-6-(2-hydroxyphenyl)pyrimidin-2(1H)-yl]cyanamide (10). The IR spectrum of compound 10 showed characteristic absorption band at 2190 cm -1 assigned to the C≡N group.…”

Chemical Constituents with Free-Radical- Scavenging Activity from the Leaves of Lantana montevidensis (Spreng.) Briq.

“…[1][2][3] The leaves methanolic extract and the flavonoid fraction from the leaves presented anti-proliferative activity against tumor cells in vitro. 4 The leaves essential oil in addition to the ethanolic extracts of the leaves and roots exhibited promising antimicrobial activity. 2,3,[5][6][7] Furthermore, the 70% aqueous methanolic extract of the leaves presented antibacterial, anti-inflammatory, anti-pyretic, antioxidant and analgesic activities.…”

“…4,9 Our previous phytochemical study on 70% methanolic extract of L. montevidensis leaves led to the isolation of pentacyclic triterpenoids. 10 In continuation of our investigation, we report herein the isolation and identification of seven flavonoids (1)(2)(3)(4)(5)(6)(7) in addition to salicylic acid (8) and β-sitosterol-3-O-glucoside (9). Furthermore, some of the isolated flavonoids were evaluated for their free radical scavenging activity.…”