Natural products as leads to anticancer drugs.

Throughout history, natural products have afforded a rich source of compounds that have found many applications in the fields of medicine, pharmacy and biology. Within the sphere of cancer, a number of important new commercialised drugs have been obtained from natural sources, by structural modification of natural compounds, or by the synthesis of new compounds, designed following a natural compound as model. The search for improved cytotoxic agents continues to be an important line in the discovery of modern anticancer drugs. The huge structural diversity of natural compounds and their bioactivity potential have meant that several products isolated from plants, marine flora and microorganisms can serve as "lead" compounds for improvement of their therapeutic potential by molecular modification. Additionally, semisynthesis processes of new compounds, obtained by molecular modification of the functional groups of lead compounds, are able to generate structural analogues with greater pharmacological activity and with fewer side effects. These processes, complemented with high-throughput screening protocols, combinatorial chemistry, computational chemistry and bioinformatics are able to afford compounds that are far more efficient than those currently used in clinical practice. Combinatorial biosynthesis is also applied for the modification of natural microbial products. Likewise, advances in genomics and the advent of biotechnology have improved both the discovery and production of new natural compounds.

Natural products as leads to anticancer drugs

Throughout history, natural products have afforded a rich source of compounds that have found many applications in the fields of medicine, pharmacy and biology. Within the sphere of cancer, a number of important new commercialised drugs have been obtained from natural sources, by structural modification of natural compounds, or by the synthesis of new compounds, designed following a natural compound as model. The search for improved cytotoxic agents continues to be an important line in the discovery of modern anticancer drugs. The huge structural diversity of natural compounds and their bioactivity potential have meant that several products isolated from plants, marine flora and microorganisms can serve as "lead" compounds for improvement of their therapeutic potential by molecular modification. Additionally, semisynthesis processes of new compounds, obtained by molecular modification of the functional groups of lead compounds, are able to generate structural analogues with greater pharmacological activity and with fewer side effects. These processes, complemented with high-throughput screening protocols, combinatorial chemistry, computational chemistry and bioinformatics are able to afford compounds that are far more efficient than those currently used in clinical practice. Combinatorial biosynthesis is also applied for the modification of natural microbial products. Likewise, advances in genomics and the advent of biotechnology have improved both the discovery and production of new natural compounds (AU)

Pharmacological and phytochemical studies of Cephäelis axillaris.

The most significant effect, observed in the preliminary pharmacological evaluation of the whole ethanol extract and the alkaloidal fraction of Cephäelis axillaris, was the hyperemia of ears and external mucosas which was most probably due to an alpha-adrenergic blocking activity. In addition, both samples also induced a marked hypotension in normotensive as well as hypertensive (SHR) rats and inhibited the increases of blood pressure induced by i.v. administration of noradrenaline in pithed rats. The structures of the major alkaloidal components of the extract were elucidated on the basis of chemical characterization assays and IR, UV, 1H and 13C one and two-dimensional NMR analyses.

Abietane acids: sources, biological activities, and therapeutic uses.

The biological activities of natural abietane acids and their derivatives have been reviewed from 1967 to 1992. Antimicrobial, antiulcer, and cardiovascular activities are the most representative for this class of diterpenoids, while others like allergenic, antiallergic, filmogenic, surfactant, antifeedant, etc. activities, which determine several uses of abietane acids, have also been reported.

Antineoplastic and antiviral activities of some cyclolignans.

Nineteen cyclolignans of varied structures, most of them isolated from Juniperus sabina leaves, were evaluated for their antineoplastic and antiviral activities. They were subjected to screening against P-388 murine leukemia, A-549 human lung carcinoma, and HT-29 colon carcinoma, while the antiviral assays were performed on herpes simplex virus type 1 infecting fibroblasts of monkey kidney (HSV-1/CV-1) and on vesicular stomatitis virus infecting fibroblasts of hamster kidney (VSV/BHK). A number of substances were active in both types of assays at concentrations below 1 microgram/ml; deoxypodophyllotoxin and beta-peltatin A methyl ether being the most potent compounds in all cases, with IC50 values in the range 2.5-4 ng/ml for the three neoplastic systems.