The goal of this research is to study the antimicrobial agents present in higher plant extracts in order to discover antibiotics with novel structures and novel modes of action and to determine their potential for use in treatment of human infectious diseases. Novel antibiotics are especially sought for the treatment of contemporarily troublesome diseases against which current fermentation-based antibiotics are not fully satisfactory for reasons of toxicity, low potency, microbial resistance, poor pharmacokinetic characteristics, and the like. Central to this effort is the obtention and botanical identification of suitable plant material, extraction, screening against a battery of disease indicator organisms used in industrial screening programs, bioassay directed fractionation, physico-chemical structure determination, synthesis (where indicated for structural clarification, preparation of substantial quantities, optomization of structure-activity relationships, etc.), evaluation of in vitro antimicrobial spectrum and potency in comparison with established antibiotics and in vivo evaluation in infected experimental animals. The latter is usually done off-side by commercial pharmaceutical firms possessing special facilities and expertise for this work. In some cases directed biosynthetic methodology is employed in order to prepare especially desired target molecules. The present emphasis of the primary screen is activity against Gram-positive and Gram-negative bacteria, tuberculosis, yeast and fungi and pseudomonads. In secondary screens, venereal organisms, anaerobes, Legionella and other pathogens are examined.
