Genomic and genetic approaches for the identification of antifungal drug targets.

Understanding how novel antifungal compounds work in target cells is useful not only in facilitating the discovery of new drugs but also new tools that can be used for further exploration of the targeted biological pathways and their regulation. Various genomic and genetic technologies have been developed in the model yeast Saccharomyces cerevisiae, and have been successfully used to identify drug target pathways. This review discusses the methods developed for some of these technologies, and how they have been used to evaluate the cellular pathways affected by a variety of therapeutic drugs and inhibitors. The advantages and disadvantages of each method are considered, and new advances are highlighted where applicable. The investigation of the mechanism of action of new antifungal compounds will undoubtedly lead to the development of new antifungal therapies targeting new fungal pathways that are more specific and less toxic than currently available antifungal drugs.

Phenolic compounds from Miconia myriantha inhibiting Candida aspartic proteases.

Assay-guided fractionation of the ethanol extract of the twigs and leaves of Miconia myriantha yielded two new compounds, mattucinol-7-O-[4' ',6' '-O-(S)-hexahydroxydiphenoyl]-beta-D-glucopyranoside (1) and mattucinol-7-O-[4' ',6' '-di-O-galloyl]-beta-D-glucopyranoside (2), along with mattucinol-7-O-beta-D-glucopyranoside (3), ellagic acid (4), 3,3'-di-O-methyl ellagic acid-4-O-beta-D-xylopyranoside, and gallic acid. Complete (1)H and (13)C NMR assignments of compound 1, which possesses a hexahydroxydiphenoyl unit, were achieved using the HMBC technique optimized for small couplings to enhance the four-bond and two-bond H/C correlations. Compounds 1 and 4 showed inhibitory effects against Candida albicans secreted aspartic proteases, with IC(50) of 8.4 and 10.5 microM, respectively.

A new naphthopyrone derivative from Cassia quinquangulata and structural revision of quinquangulin and its glycosides.

A novel naphthopyrone derivative, named quinquangulone (1), has been isolated from Cassia quinquangulata, along with the known compounds quinquangulin (2) and its two glycosides (3 and 4), rubrofusarin (5) and its two glycosides (6 and 7), nor-rubrofusarin (8) and its 6-O-glucoside (9), and three stilbenes (10-12). The structure of quinquangulone was established by spectral interpretation as 5,9-dihydroxy-8-methoxy-2,9-dimethyl-6-oxo-4H,6H,9H-naphtho-[2,3-b]pyran-4-one. Reinvestigation of the NMR spectra of quinquangulin led to revision of its structure as 5,6-dihydroxy-8-methoxy-2,9-dimethyl-4H-naphtho[2,3-b]pyran-4-one (2a). The structures of two quinguangulin glycosides, 3 and 4, were also revised accordingly. Compound 2a exhibited activity against Staphylococcus aureus and methicillin-resistant S. aureus (MIC, 3.125 and 6.25 microg/mL, respectively).

Ethical boundaries and health maintenance organization (HMO) expectations: who draws the line?

Observes that although HMO expectations continue to expand with an increase of responsibilities for the pastoral counselor, the benefits have not maintained pace with the responsibilities. Asks, "Where and how does the pastoral counselor draw the line of personal limits? When limitations are set, how does the pastoral counselor represent the ethical values of the profession and the religious community?" Argues that there are subjective and objective considerations and judgements needed to test the ethics of where and how such limitations are established.

New indole alkaloids from the bark of Nauclea orientalis.

Four new alkaloids, nauclealines A (1) and B (2) and naucleosides A (3) and B (4), together with six known compounds, strictosamide (5), vincosamide (6), pumiloside (7), kelampayoside A, sitosterol, and sitosteryl beta-D-glucoside, were isolated from the bark of Nauclea orientalis. The structures of 1-4 were elucidated using 1D and 2D NMR spectral methods, including COSY, DEPT, HMQC, (13)C-(1)H HMBC, and (15)N-(1)H HMBC.