Simple (Bench-Top) Bioassays and the Isolation of New Chemically Diverse Antitumor and Pesticidal Agents from Higher Plants

Abstract

A review with 132 refs. Four simple (bench-top) bioassays are serving well for the detection and fractionation monitoring of new plant antitumor and pesticidal agents. These are: (1) lethality to the larvae of brine shrimp (Artemia salina); (2) the inhibition of crown gall tumors, induced by plasmid transfer and expression from Agrobacterium tumefaciens, on disks of potato (Solanum tuberosum) tubers; (3) the inhibition or stimulation of frond proliferation of duckweed (Lemna minor); and (4) lethality to the larvae of yellow fever mosquitoes (Aedes aegyptii). Since 1984, over 320 chem. diverse bioactive plant components have been isolated and characterized in our lab. by using these methods. Recently, bioactive compds. from the Meliaceae, Lauraceae, Euphorbiaceae, Laminaceae, and other plant families have been isolated, but our most exciting leads have been with the potent acetogenins from the Annonaceae; these compds. are powerful inhibitors of mitochondrial electron transport systems and of the NADH oxidase that is prevalent in the plasma membranes of tumorous cells. The consequence is ATP depletion, and this is esp. toxic to multiple drug resistant tumor cells and pesticide resistant insects that possess ATP-dependent xenobiotic efflux systems. Structural activity relationship studies (in mitochondrial prepns. and against mosquito larvae) help to define the optimum structural features. This paper has presented the chem. and biol. testing results of 207 plant components recently isolated using the simple bioassays described followed by cytotoxicity testing in a panel of six human tumor cell lines. [on SciFinder(R)]