Antimicrobial Coumarins from the Oyster Culinary-Medicinal Mushroom, Pleurotus ostreatus (Agaricomycetes), from Kenya.

Pleurotus ostreatus has been widely used as food because of its nutritional and medicinal properties. These have been attributed to the presence of macronutrients, minerals, vitamins, and amino acids, among other secondary metabolites. There are, however, few reports on the antimicrobial activities of different classes of purified compounds from P. ostreatus. This led to the current study, the objective of which was to chemically characterize the antibiotic activities of P. ostreatus against selected human pathogenic bacteria and endophytic fungi. Chemical structures were determined using spectroscopic methods and by comparison with values of related structures reported in the literature. Pure compounds from P. ostreatus were tested in vitro against pathogenic bacteria (Staphylococcus aureus and Escherichia coli) and endophytic fungi (Pencillium digitatum and Fusarium proliferatum). A new compound, (E)-5,7-dimethoxy-6-(3-methylbuta-1,3-dienyl)-2H-chromen-2-one (5-methoxy-(E)-suberodiene) (compound 2), along with ergosterol (compound 1) and 5,7-dimethoxy-6-(3-methylbut-2-enyl)-2H-chromen-2-one (toddaculin; compound 3), were isolated from the fruiting bodies of P. ostreatus. The growth of S. aureus, F. proliferatum, and P. digitatum colonies was inhibited in media containing compound 2, with minimum inhibitory concentrations closely comparable to those of conventional antibiotics.

Antimicrobial compounds from root, stem bark and seeds of Melia volkensii.

Three compounds, toosendanin (1), kulactone (2) and scopoletin (3), were isolated from either the root bark and/or the stem bark of Melia volkensii. Their structures were determined on the basis of spectroscopic data generated and by comparison with data from the literature. 1 and 2, isolated for the first time from M. volkensii, exhibited significant (p < 0.05) activity against Escherichia coli with minimum inhibitory concentration of 12.5 µg/mL, close to that of neomycin (6.25 µg/mL). The compounds also exhibited high activity against Aspergillus niger (MIC 6.25 µg/mL compared to 2.5 µg/mL for clotrimazole). Dichloromethane and methanol seed, hexane stem bark and methanol root bark extracts exhibited activities towards Escherichia coli, Staphylococcus aureus, Aspergillus niger and Plasmodium falciparum, respectively. Antimicrobial activity of the plant towards A. niger, P. falciparum and S. aureus is reported for the first time in the current work.

Micelles of TPGS modified apigenin phospholipid complex for oral administration: preparation, in vitro and in vivo evaluation.

Mixed micelles were designed to increase oral bioavailability of Apigenin (Ap). The phospholipid (Ph) complex technology was exploited alongside TPGS' stabilizing effect by PEG chain sterical hindrance of the phase II enzymes. This prevented extensive metabolism of Ap while inhibiting P-glycoprotein's exocytosis. TPGS modified micelles of Ap-Ph complex (TPGS-Ap-Ph) were prepared by thin film hydration method. Ap-Ph complex was confirmed by FTIR and NMR spectroscopy while Ap, Ph and TPGS interactions were studied by surface tensiometry. TPGS-Ap-Ph micelles achieved 87.35% drug encapsulation and 12.6% drug loading showing spherical morphology 137.1 +/- 3.4 nm particle size and -12.94 mV surface charge. The negative zeta potential confirmed computer simulation predictions that PEG moieties of TPGS were at micelles surface, while hydrophobic part inserted to the phospholipid hydrophobic core by electrostatic interactions. TPGS-Ap-Ph micelles were found to be stable for more than 90 days after lyophilization. Comparing to free drug, the micelles increased intestinal absorption of Ap 2.4 fold, illustrating apparent permeation (P(app)) and absorption constant (K(a)) of 7.9 x 10(-4) and 2.05 x 10(-4) (p < 0.001) respectively. Moreover, cell culture studies showed high cellular uptake with sufficient intracellular trafficking in A549 cells. MTT assays revealed a significant cytotoxic effect by TPGS-Ap-Ph micelles. In vivo, an effective inhibition of 72.9% was achieved upon oral administration to S180 carcinoma mice compared to 19.5% by Ap-Ph complex. Altogether reflect that orally administered mixed micelles of TPGS-Ap-Ph could effectively inhibit cancer. The results present the designed micelles as a new way to improve oral bioavailability of sparingly soluble and poorly absorbed drugs.

Cell penetrating peptides in the delivery of biopharmaceuticals.

The cell membrane is a highly selective barrier. This limits the cellular uptake of molecules including DNA, oligonucleotides, peptides and proteins used as therapeutic agents. Different approaches have been employed to increase the membrane permeability and intracellular delivery of these therapeutic molecules. One such approach is the use of Cell Penetrating Peptides (CPPs). CPPs represent a new and innovative concept, which bypasses the problem of bioavailability of drugs. The success of CPPs lies in their ability to unlock intracellular and even intranuclear targets for the delivery of agents ranging from peptides to antibodies and drug-loaded nanoparticles. This review highlights the development of cell penetrating peptides for cell-specific delivery strategies involving biomolecules that can be triggered spatially and temporally within a cell transport pathway by change in physiological conditions. The review also discusses conjugations of therapeutic agents to CPPs for enhanced intracellular delivery and bioavailability that are at the clinical stage of development.

Antifungal rosane diterpenes and other constituents of Hugonia castaneifolia.

The rosane diterpenoids hugorosenone [3beta-hydroxyrosa-1(10),15-dien-2-one], 18-hydroxyhugorosenone and 18-hydroxy-3-deoxyhugorosenone, and 12-hydroxy-13-methylpodocarpa-8,11,13-trien-3-one were isolated as antifungal constituents of H. castaneifolia Engl. root bark, together with the previously reported di-podocarpanoids hugonone A and hugonone B that were weakly active, and 1(10),15-rosadiene-2beta,3beta-diol (hugorosenol), 4alpha-methoxyhimachal-10-en-5beta-ol (hugonianene B) and 2-hydroxyhenpentacont-2-enal, and the known compounds tetracosyl-(E)-ferrulate and caryophyllene oxide, all of which were inactive. Hugorosenone also exhibited activity against Anopheles gambiae mosquito larvae. Structural determination was achieved based on spectroscopic data.

A new cytotoxic and larvicidal himachalenoid, rosanoids and other constituents of Hugonia busseana.

A new cytotoxic himachalene sesquiterpenoid 4alpha-methoxy-5,9-oxahimachal-9-ene (hugonianene A) which exhibited moderate activity against Anopheles gambiae mosquito larvae after 24 h at a concentration of 0.237 mg mL(-1), and at 48 h and 72 h contact time causing complete larval mortality up to a concentration as low as 0.01369 mg mL(-1), was isolated as the major constituent of the cytotoxic root bark extract of Hugonia busseana. Hugonianene A was obtained together with the hitherto unreported rosane diterpenoid 18-hydroxyrosane, the known rosane diterpenoid hugorosediol, an inseparable mixture of 12-methoxy-13-methylpodocarpa-8,11,13-trien-3,7-dione and 12-methoxy-13-methylpodocarpa-1,8,11,13-tetraen-3,7-dione, and the di-podocarpanoid hugonone B that was previously obtained from H. castaneifolia.

C18 tetraynoic fatty acids and essential oil composition of Mkilua fragrans.

The fatty acids 17,18-dihydroxyoctadeca-9,11,13,15-tetraynoic acid (mkiluaynoic acid A) and 18-hydroxyoctadeca-9,11,13,15-tetraynoic acid (mkiluaynoic acid B), 5,7,3',4'-tetrahydroxyflavanol, 3,4-dihydroxybenzoic acid and a mixture of stearic and oleic acids were isolated from fruits and stem barks of Mkilua fragrans (Annonaceae). Mkiluaynoic acid A exhibited antifungal activity against Candida albicans comparable with that of the standard antifungal agent Ketoconazole. Structural determination was achieved by analysis of spectroscopic data. The flower stalks yielded essential oils that mainly consisted of sesquiterpenoids as revealed by GC-MS analysis, whereby 14 sesquiterpenes and four other compounds were identified.