Identification of Anticryptococcal Bornyl Compounds from Verbesina turbacensis and Their Structure-Activity Relationships.

Cryptococcus neoformans is an opportunistic fungal pathogen that has limited treatment options. Natural product plant extracts offer a cost-effective option for the discovery of new anticryptococcal lead compounds. The acetone bark extract of Verbesina turbacensis was found to potently inhibit C. neoformans and was subjected to bioautography. Two compounds that inhibited the growth of C. neoformans were isolated and displayed minimum inhibitory concentration values of 10 and 310 µg/mL. The compounds were identified as the bornyl hydroxycinnamic esters bornyl caffeate and bornyl ferulate, respectively. To better understand initial structure-activity relationships, anticryptococcal activity was characterized for similar compounds. All compounds were further evaluated for mammalian cell toxicity using the MTT assay with MCF-7 and HEK-293 cell lines. Overall, bornyl caffeate demonstrated promising anticryptococcal potential given its potent inhibition of C. neoformans and low mammalian cell toxicity.

Antifungal and Cytotoxic Activities of Sixty Commercially-Available Essential Oils.

There is an urgent and unmet need for new antifungal therapies. Global fungal infection rates continue to rise and fungal infections pose increasing burdens on global healthcare systems. Exacerbating the situation, the available antifungal therapeutic arsenal is limited and development of new antifungals has been slow. Current antifungals are known for unwanted side effects including nephrotoxicity and hepatotoxicity. Thus, the need for new antifungals and new antifungal targets is urgent and growing. A collection of 60 commercially-available essential oils has been screened for antifungal activity against Aspergillus niger, Candida albicans, and Cryptococcus neoformans, as well as for cytotoxic activity against MCF-7 and MDA-MB-231 human breast tumor cell lines; the chemical compositions of the essential oils have been determined by gas chromatography-mass spectrometry (GC-MS). Ten essential oils showed remarkable antifungal and cytotoxic activities: Indian, Australian, and Hawaiian sandalwoods; melissa; lemongrass; cilantro; cassia; cinnamon; patchouli; and vetiver.

Phytochemical and Biological Investigations of Conradina canescens.

Conradina canescens (Lamiaceae) is an endemic evergreen shrub native to Florida, Mississippi and Alabama, with no phytochemical or biological studies registered in the literature. Thus, a phytochemical study and a toxicity analysis of the chloroform extract obtained from the leaves of C. canescens were performed for the first time. In our preliminary screening, the crude extract and its fractions were subjected to cytotoxicity, antimicrobial and antileishmanial bioassays. The crude extract showed substantial cytotoxic, antimicrobial and antileishmanial activities. A total of six compounds, namely ursolic acid (62.4%), betulin (8.4%), ß-amyrin (4.6%), myrtenic acid (2.9%), n-tetracosane (1.4%), and oleanolic acid (1.1%), were isolated. The structures of the isolated compounds were established by spectroscopic studies using NMR and IR spectroscopy.

Chemical compositions, phytotoxicity, and biological activities of Acorus calamus essential oils from Nepal.

Four essential oils from the leaf (P23) and rhizomes (P19, P22, P24) of Acorus calamus L., collected from various parts of Nepal, were obtained by hydrodistillation and analyzed by GC-MS. From a total of 61 peaks, 57 compounds were identified among the four essential oils accounting for 94.3%, 96.2%, 97.6%, and 94.1% of the oils, respectively. All of the essential oils were dominated by (Z)-asarone (78.1%-86.9%). The essential oils also contained (E)-asarone (1.9%-9.9%) and small amounts of gamma-asarone (2.0-2.3%), (Z)-methyl isoeugenol (1.5-2.0%), and linalool (0.2-4.3%). Allelopathic testing of the rhizome oil showed inhibition of seed germination of Lactuca sativa and Lolium perenne with IC50 values of 450 and 737 microg/mL, respectively. The rhizome essential oil demonstrated stronger seedling growth inhibition of L. perenne than of L. sativa, however. The rhizome oil also showed notable brine shrimp lethality (LC50 = 9.48 microg/mL), cytotoxic activity (92.2% kill on MCF-7 cells at 100 microg/mL), and antifungal activity against Aspergillus niger (MIC = 19.5 microg/mL).

Bioactivities of volatile components from Nepalese Artemisia species.

The essential oils from the leaves of Artemisia dubia, A. indica, and A. vulgaris growing wild in Nepal were obtained by hydrodistillation and analyzed by GC-MS. The major components in A. dubia oil were chrysanthenone (29.0%), coumarin (18.3%), and camphor (16.4%). A. indica oil was dominated by ascaridole (15.4%), isoascaridole (9.9%), trans-p-mentha-2,8-dien-1-ol (9.7%), and trans-verbenol (8.4%). The essential oil of Nepalese A. vulgaris was rich in alpha-thujone (30.5%), 1,8-cineole (12.4%), and camphor (10.3%). The essential oils were screened for phytotoxic activity against Lactuca sativa (lettuce) and Lolium perenne (perennial ryegrass) using both seed germination and seedling growth, and all three Artemisia oils exhibited notable allelopathic activity. A. dubia oil showed in-vitro cytotoxic activity on MCF-7 cells (100% kill at 100 microg/mL) and was also marginally antifungal against Aspergillus niger (MIC = 313 microg/mL). DFT calculations (B3LYP/6-31G*) revealed thermal decomposition of ascaridole to be energetically accessible at hydrodistillation and GC conditions, but these are spin-forbidden processes. If decomposition does occur, it likely proceeds by way of homolytic peroxide bond cleavage rather than retro-Diels-Alder elimination of molecular oxygen.

Attenuation of cytotoxic natural product DNA intercalating agents by caffeine.

Many anti-tumor drugs function by intercalating into DNA. The xanthine alkaloid caffeine can also intercalate into DNA as well as form π-π molecular complexes with other planar alkaloids and anti-tumor drugs. The presence of caffeine could interfere with the intercalating anti-tumor drug by forming π-π molecular complexes with the drug, thereby blocking the planar aromatic drugs from intercalating into the DNA and ultimately lowering the toxicity of the drug to the cancer cells. The cytotoxic activities of several known DNA intercalators (berberine, camptothecin, chelerythrine, doxorubicin, ellipticine, and sanguinarine) on MCF-7 breast cancer cells, both with and without caffeine present (200 µg/mL) were determined. Significant attenuation of the cytotoxicities by caffeine was found. Computational molecular modeling studies involving the intercalating anti-tumor drugs with caffeine were also carried out using density functional theory (DFT) and the recently developed M06 functional. Relatively strong π-π interaction energies between caffeine and the intercalators were found, suggesting an "interceptor" role of caffeine protecting the DNA from intercalation.

A phytochemical investigation of Zanthoxylum setulosum.

The crude bark extract of Zanthoxylum setulosum from Monteverde, Costa Rica was notably cytotoxic (100% kill at 100 microg/mL) to MCF-7, MDA-MB-231, and MDA-MB-468 cells in vitro. Phytochemical studies of the bark extract revealed the triterpenoid lupeol, the lignan sesamin, the sesquiterpene sesquichamaenol, and the xanthone lichexanthone. This is the first report of the isolation of sesquichamaenol and lichexanthone from the bark extract of Z. setulosum. All structures were determined using NMR spectroscopic techniques (1H NMR and 13 degrees C NMR) and GC-MS and by comparison with literature data. Lupeol proved to be the cytotoxic component of Z. setulosum bark.

Essential oil compositions and cytotoxic activities of Dendropanax capillaris, Oreopanax nubigenus, and Schefflera rodrigueziana from Monteverde, Costa Rica.

The leaf essential oils of Dendropanax capillaris, Oreopanax nubigenus and Schefflera rodrigueziana (Araliaceae) were isolated by hydrodistillation and analyzed by GC-MS. The leaf oil of Dendropanax capillaris was composed of only four compounds, beta-pinene (25.3%), 6-3-carene (44.7%), daucene (17.1%), and dauca-5,8-diene (12.9%). Oreopanax nubigenus leaf oil was dominated by the sesquiterpene hydrocarbons germacrene D (70.1%) and beta-caryophyllene (11.8%), while Schefflera rodrigueziana leaf oil was made up entirely of sesquiterpene hydrocarbons, mostly germacrene D (27.6%), beta-cubebene (27.2%), beta-caryophyllene (12.2%), beta-cubebene (11.1%), and alpha-copaene (10.8%). Both O. nubigenus and S. rodrigueziana leaf oils showed notable in-vitro cytotoxicity on MDA-MB-231 cells, which may be attributable to the relatively high concentrations of germacrene D and beta-caryophyllene in those oils.

Phytomedicinal potential of tropical cloudforest plants from Monteverde, Costa Rica

A pharmacological survey of plants from Monteverde, Costa Rica, including 165 species representing 61 families has been carried out. Crude plant extracts have been tested for in-vitro bactericidal and fungicidal activity as well as cytotoxic and anti-herpes activity. Of these, 123 extracts exhibited notable cytotoxicity, 62 showed antibacterial activity, 4 showed antifungal activity, and 8 showed promising antiviral activity. Thus, 101 of the plant species examined in this work, or 62, showed marked bioactivity in one or more bioassays. These results underscore the phytomedicinal potential of Neotropical cloud forests.

Phytomedicinal potential of tropical cloudforest plants from Monteverde, Costa Rica.

A pharmacological survey of plants from Monteverde, Costa Rica, including 165 species representing 61 families has been carried out. Crude plant extracts have been tested for in-vitro bactericidal and fungicidal activity as well as cytotoxic and anti-herpes activity. Of these, 123 extracts exhibited notable cytotoxicity, 62 showed antibacterial activity, 4 showed antifungal activity, and 8 showed promising antiviral activity. Thus, 101 of the plant species examined in this work, or 62%, showed marked bioactivity in one or more bioassays. These results underscore the phytomedicinal potential of Neotropical cloud forests.