The pyridoacridine family tree: a useful scheme for designing synthesis and predicting undiscovered natural products.

The pyridoacridine natural products represent a large and growing class and serve here to illustrate the wealth of information that can be extracted by comparing natural products on the basis of structure and occurrence.

A simple biomimetic synthesis of styelsamine B.

An extremely rapid, low cost, and environmentally friendly entry into the pyridoacridine family of alkaloids has been devised, as demonstrated here by the first total synthesis of styelsamine B (3) and its oxidation to the quinoneimine cystodytin J (4). The known reaction of cystodytin J with methanethiol makes this a formal synthesis of diplamine. [reaction: see text]

Synthesis and screening of small molecule libraries active in binding to DNA.

Five synthetic combinatorial libraries of 2,080 components each were screened as mixtures for inhibition of DNA binding to two transcription factors. Rapid, solution-phase synthesis coupled to a gel-shift assay led to the identification of two compounds active at a 5- to 10-microM concentration level. The likely mode of inhibition is intercalation between DNA base pairs.

The effect of cadmium on the formation and properties of hydroxyapatite in vitro and its relation to cadmium toxicity in the skeletal system.

In order to understand the biological action of cadmium (Cd) in inducing bone pathologies, the effect of Cd on the formation, structure, and properties of hydroxyapatite (HA) in vitro was investigated using three biologically relevant test systems: (1) direct precipitation of HA with no precursor phase; (2) transformation of amorphous calcium phosphate (ACP) to crystalline HA; and (3) growth of HA seed crystals. Cd-containing HA was prepared by transforming ACP to HA in the presence of Cd at a pH of 10; Cd/Ca ratios of 0.05, 0.

Algorithms for adjustment of insulin dosage by patients who monitor blood glucose.

Patient self-monitoring of blood glucose is a useful adjuvant to diabetes therapy that facilitates improved glycemic control when used as part of an intensive diabetes management program that includes careful balancing of food intake, energy expenditure, and insulin dosage. This paper describes an approach by which patient-determined blood glucose measurements may be used to attain and maintain glycemic control. The patient is provided with a set of algorithms by which minor adjustments in a therapeutic routine may be made to achieve the desired control.