Navigating through chemical space and evolutionary time across the Australian continent in plant genus Eremophila.

Eremophila is the largest genus in the plant tribe Myoporeae (Scrophulariaceae) and exhibits incredible morphological diversity across the Australian continent. The Australian Aboriginal Peoples recognize many Eremophila species as important sources of traditional medicine, the most frequently used plant parts being the leaves. Recent phylogenetic studies have revealed complex evolutionary relationships between Eremophila and related genera in the tribe. Unique and structurally diverse metabolites, particularly diterpenoids, are also a feature of plants in this group. To assess the full dimension of the chemical space of the tribe Myoporeae, we investigated the metabolite diversity in a chemo-evolutionary framework applying a combination of molecular phylogenetic and state-of-the-art computational metabolomics tools to build a dataset involving leaf samples from a total of 291 specimens of Eremophila and allied genera. The chemo-evolutionary relationships are expounded into a systematic context by integration of information about leaf morphology (resin and hairiness), environmental factors (pollination and geographical distribution), and medicinal properties (traditional medicinal uses and antibacterial studies), augmenting our understanding of complex interactions in biological systems.

Chemical and biological characterization of novel essential oils from Eremophila bignoniiflora (F. Muell) (Myoporaceae): a traditional Aboriginal Australian bush medicine.

Essential oils were extracted by hydrodistillation from the traditional Australian medicinal plant Eremophila bignoniiflora, characterized chemically and then screened for bioactivity. Characterization and quantification were completed using gas chromatography-mass spectrometry (GC-MS) and GC-flame ionization detection, respectively. Antimicrobial capacity was assessed using disc diffusion and micro-titre plate broth dilution and further characterized using thin layer chromatography followed by bioautography to assign activity to separated individual active components. Antifungal capacity was investigated using micro-titre plate broth dilution against pathogenic Trichophyton species. Free radical scavenging ability was assessed using the diphenylpicrylhydradyl reaction in methanol. The predominant components of the essential oil were fenchyl-acetate and bornyl-acetate. However, bioautography indicated antimicrobial ability to be largely linked to the less abundant, more polar constituents. Oils displayed only modest antifungal ability against pathogenic Trichophyton species associated with dermatophytosis, but moderate to high antimicrobial activity, particularly against the yeast Candida albicans and the bacteria Staphylococcus epidermidis. Essential oils exhibited relatively low free radical scavenging ability. Speculation over the role of essential oils in the traditional medicinal applications of E. bignoniiflora follows, exploring correlations between traditional use and investigated bioactivities.

In vitro anti-proliferation/cytotoxic activity of epingaione and its derivatives on the human SH-SY5Y neuroblastoma and TE-671 sarcoma cells.

Epingaione (4-Methyl-1-(5-methyl-2, 3,4,5-tetrahydro-[2,3']bifuranyl-5-yl)-pentan-2-one) was isolated as one of the major lipophilic secondary metabolites from the leaves and stems of Bontia daphnoides L. The compound gave 79.24% and 50.83% anti-proliferation/cytotoxic activity on the human SH-SY5Y neuroblastoma and TE-671 sarcoma cells in vitro at 50 pg/mL, respectively. Epingaione was transformed into eleven derivatives under laboratory conditions using ethanol, some gave greater anti-proliferation/cytotoxic activity on the cancer cell lines tested. One of the derivatives (compound 2) with enhanced cytotoxic activity was elucidated as 5'-Ethoxy-5-methyl-5-(4-methyl-2-oxo-pentyl)-2,3,4,5-tetrahydro-5'H-[2,3']bifuranyl-2'-one. Both epingaione and compound 2 caused an accumulation of arrested or dead SH-SY5Y neuroblastoma in the m-phase of the cell cycle as revealed by the m-phase specific marker KE 67.

Identification of antibacterial constituents from the indigenous Australian medicinal plant Eremophila duttonii F. Muell. (Myoporaceae).

This paper reports on the isolation and identification of antibacterial constituents from the indigenous Australian medicinal plant Eremophila duttonii F. Muell. (Myoporaceae). Preparations derived from this plant are used by indigenous populations in the topical treatment of minor wounds, otitis and ocular complaints, and as a gargle for sore throat. Several authors have reported extracts of this plant to effect rapid bacteriolysis and inhibit growth of a wide range of Gram-positive micro-organisms. In other studies involving screening of native medicinal plants for antibacterial activity, extracts of Eremophila duttonii have been reported to consistently exhibit the highest potency amongst all species included. From a hexane extract, we identified two diterpenes of the serrulatane class, the principal constituents responsible for antibacterial activity and present as major constituents of the resinous leaf cuticle: serrulat-14-en-7,8,20-triol (1) and serrulat-14-en-3,7,8,20-tetraol (2). In addition, a hydroxylated furanosesquiterpene with mild antibacterial activity which appeared to be a novel compound was isolated from the extract and tentatively identified as 4-hydroxy-4-methyl-1-(2,3,4,5-tetrahydro-5-methyl[2,3'-bifuran]-5-yl) pentan-2-one. Minimum inhibitory concentrations for each of the compounds against three Gram-positive bacteria: Staphylococcus aureus (ATCC 29213), Staphylococcus epidermidis (ATCC 12228) and Streptococcus pneumoniae (ARL 10582), were determined using a micro-titre plate broth dilution assay.

In vitro anti-proliferation/cytotoxic activity of epingaione and its derivatives on the human SH-SY5Y neuroblastoma and TE-671 sarcoma cells / Actividad citotóxica antiproliferativa in vitro de la epingaiona y sus derivados, sobre el neuroblastoma humano sh-sy5y y las células del sarcoma te-671

Epingaione (4-Methyl-1-(5-methyl-2, 3,4,5-tetrahydro-[2,3']bifuranyl-5-yl)-pentan-2-one) was isolated as one of the major lipophilic secondary metabolites from the leaves and stems of Bontia daphnoides L. The compound gave 79.24and 50.83anti-proliferation/cytotoxic activity on the human SH-SY5Y neuroblastoma and TE-671 sarcoma cells in vitro at 50 pg/mL, respectively. Epingaione was transformed into eleven derivatives under laboratory conditions using ethanol, some gave greater anti-proliferation/cytotoxic activity on the cancer cell lines tested. One of the derivatives (compound 2) with enhanced cytotoxic activity was elucidated as 5'-Ethoxy-5-methyl-5-(4-methyl-2-oxo-pentyl)-2,3,4,5-tetrahydro-5'H-[2,3']bifuranyl-2'-one. Both epingaione and compound 2 caused an accumulation of arrested or dead SH-SY5Y neuroblastoma in the m-phase of the cell cycle as revealed by the m-phase specific marker KE 67.

La epingaiona (4-Metil-1-(5-metil-2,3,4,5-tetrahidro-[2,3']bifuranil-5-il)-pentan-2-uno) fue aislada como uno de los principales metabolitos lipofilicos secundarios de las hojas y tallos de Bontia daphnoides L. El compuesto produjo 79.24 % y 50.83 % de actividad citotóxica/anti-proliferación sobre el neuroblastoma humano SH-SY5Y y las células del sarcoma TE-671 in vitro a 50 µg/mL, respectivamente. La epingaiona fue transformada en once derivados en condiciones de laboratorio, utilizando etanol. Algunos produjeron mayor actividad citotóxica y antiproliferativa sobre las líneas celulares cancerosas sometidas a ensayo. Uno de los derivados (compuesto 2) de elevada actividad citotóxica fue identificado como 5'-Etoxi-5-metil-5-(4-metil-2-oxo-pentil)-2,3,4,5-tetrahidro-5'H- [2,3']bifuranil-2'-uno. Tanto la epingaiona como el compuesto 22 causaron una acumulación de neuroblastomas SH-SY5Y muertos o detenidos en la fase m del ciclo celular, según lo revela el marcador KE 67 específico de la fase m.