The history of drug development has its foundation firmly set in the study of natural remedies used to treat human disease over centuries. Analysis of medicinal plants, bioactive cultures, and increased understanding of micronutrients in the food chain opened the door to the development of purified and defined chemical compounds as dose-controlled medicines. Thus, with the early discovery of cardiotonics in foxglove, salicylic acid in willow bark, morphine in poppies, and penicillin in mold, the pharmaceutical industry was launched. Such natural small molecules served as treatments for disease and ultimately, as pharmacologic tools to enable the understanding of the biochemical pathways and mechanisms of disease. In contrast, modern drug discovery technologies coupled with the powerful tools of biotechnology have prompted drug discovery organizations to focus on target-driven drug discovery at the molecular level by launching high-throughput screening programs using artificial biochemical assays. At a time when the pharmaceutical industry has come under scrutiny for high rates of drug development failure, it is interesting to see that natural products drug discovery has been marginalized in favor of this high-throughput biochemical screening paradigm. If modern drug development is once again to benefit from natural products as a source, then the limitations of artificial biochemical assays as applied to the screening of natural extracts must be realized in order to capitalize on the vast natural molecular diversity and rich ethnobotanic data that has emerged worldwide. Natural compounds can again become central players in the treatment of disease and in the understanding of disease mechanisms.

Natural products as a robust source of new drugs and drug leads: past successes and present day issues.

Assays of digitalis in the blood.

Three new (1–3) and two known (4 and 5) cytotoxic cardiac glycosides were isolated and characterized from a medicinal plant, Streblus asper Lour. (Moraceae), collected in Vietnam, with six new analogues and one known derivative (5a–g) synthesized from (+)-strebloside (5). A preliminary structure–activity relationship study indicated that the C-10 formyl and C-5 and C-14 hydroxy groups and C-3 sugar unit play important roles in the mediation of the cytotoxicity of (+)-strebloside (5) against HT-29 human colon cancer cells. When evaluated in NCr nu/nu mice implanted intraperitoneally with hollow fibers facilitated with either MDA-MB-231 human breast or OVCAR3 human ovarian cancer cells, (+)-strebloside (5) showed significant cell growth inhibitory activity in both cases, in the dose range 5–30 mg/kg.

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Cardiac Glycoside Constituents of Streblus asper with Potential Antineoplastic Activity

Higher plants are well known for their value in affording clinically useful anticancer agents, with such compounds acting against cancer cells by a range of mechanisms of action. There remains a strong interest in the discovery and development of plant secondary metabolites as additional cancer chemotherapeutic lead compounds. In the present review, progress on the discovery of plant-derived compounds of the biflavonoid, lignan, sesquiterpene, steroid, and xanthone structural types is presented. Several potential anticancer leads of these types have been characterized from tropical plants collected in three countries as part of our ongoing collaborative multi-institutional project. Preliminary structure–activity relationships and work on in vivo testing and cellular mechanisms of action are also discussed. In addition, the relevant work reported by other groups on the same compound classes is included herein.

Potential Anticancer Agents Characterized from Selected Tropical Plants.

Studien zum vorgang der wasserstoffübertragung—33. Zur kenntnis des aufbaus der elektrochemischen doppelschicht. Die asymmetrische elektrochemische reduktion einiger alkyl-phenyl-ketone in gegenwart optisch aktiver leitsalze☆

Sydney Smith

Papers

LXXII.—Digoxin, a new digitalis glucoside

CCCXXVI.—Digitalis glucosides. Part II. Digoxigenin, the aglucone of digoxin

CCLXX.—l-Methylephedrine, an alkaloid from Ephedra species

VII.—Nor-d-ψ-ephedrine, an alkaloid from Ephedra species

II.—Digitalis glucosides. Part III. Glucosides of Digitalis lanata