Cytotoxic Clerodane Diterpenoids from Fruits of Casearia grewiifolia

Abstract

Bioactivity-guided fractionation of the ethyl acetate-soluble fraction of a methanol extract of the fruits of Casearia grewiifolia afforded eight new clerodane diterpenes, caseargrewiins E-L (1-8), and a known clerodane diterpene, esculentin B (9). The structures of 1-8 were established on the basis of 1D and 2D NMR spectroscopic data. Most of these compounds exhibited cytotoxicity against three cancer cell lines with IC50 values in the range 0.15-6.00 microg/mL.

Cytotoxic activity of Brazilian Cerrado plants used in traditional medicine against cancer cell lines

“…extracts of Casearia membranacea leaves and twigs (Shen et al, 2004;Shen et al, 2005) and roots ; Casearia nigrescens leaves and flowers (Williams et al, 2007); Casearia grewiifola fruits (Kanokmedhakul et al, 2007) and bark (Kanokmedhakul et al, 2005); and Casearia lucida bark (Sai Prakash et al, 2002). Casearia sylvestris var.…”

Reactivity of (3-Methylpentadienyl)iron(1+) Cation: Late-stage Introduction of a (3-Methyl-2Z,4-pentadien-1-yl) Side Chain

“… 135, 114 and 20 ppm respectively. These chemical shifts are characteristic of a 3-methyl-2Z,4-pentadienyl group [2][3][4][5] . This was found to be in sharp contrast to the chemical shifts reported 9 for H14 ( 6.37 ppm) C14, C15 and the dienyl methyl C16 ( 141.7, 111.1 and 12.1 ppm) of the sidechain of heteroscyphic acid methyl ester.…”

“…For example, (+)-striatene 1 (1, Figure 1), and the labdane diterpenes (+)-solidagol 2 2 and (-)-ent-3 -acetoxylabda-8(17),12Z,14-trien-2-ol 3 3 were isolated from the liverwort Ptychanthus striatus, from Canadian golden rod (Solidago canadensis) and from the ornamental plant Plectranthus fruticosus respectively. Similarly, the clerodane diterpene (+)-caseargrewiin E 4 4 , isolated from a Thai shrubby tree, exhibited cytotoxic activity against KB, BC1 and NCI-H187 cancer cell lines in the range 0.15-0.91 g/mL range. In spite of these and other examples 5 , only a single synthesis of a terpene containing this functionality has been reported 6 .…”

Bothrops jararacussu venom-induced neuromuscular blockade inhibited by Casearia gossypiosperma Briquet hydroalcoholic extract

“…It includes around 180 species that occur throughout the tropics and are widespread in the Americas, Africa, Asia, Malaysia, Australia and islands of the Pacific Ocean (1). At least 16 Casearia species have shown biological activity such as cytotoxic [C. arborea; C. grayi; C. grewiifolia; C. lucida; C. multinervosa; C. nigrescens; C. obliqua (2)(3)(4)(5)(6)(7)(8)]; antifungal [C. decandra (9)]; antidiabetic [C. esculenta (10)]; immunomodulatory [C. guianensis (11)]; antifertility [C. ilicifolia (12)]; antiophidian [C. mariquitensis (13)]; antitumor [C. membranacea (14)]; genotoxic [C. tomentosa (15)]; and antioxidant actions [C. velutina (16)]. The most studied among them is Casearia sylvestris Sw. that has shown several biological activities, including antitumor, antiulcer, analgesic, anti-inflammatory, cytotoxic, antifungal, anticancer, anti-snake and bee venom PLA 2 , genotoxic, trypanocidal, enzyme inhibitory, antihyperlipidemic and antibothropic properties (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27).…”

“…After 15 minutes, the absorbance of samples was read at 420 nm, considering a blank sample containing 80% methanol (8 mL) and 5% AlCl 3 (2 mL). The percentage of flavonoids (%) was calculated from a standard curve of quercetin (0,4,8,12, and 16 µg/mL) prepared with methanol. …”