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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI013155-13
Application #
3125405
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1976-09-01
Project End
1991-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
13
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Kansas Lawrence
Department
Type
Schools of Pharmacy
DUNS #
072933393
City
Lawrence
State
KS
Country
United States
Zip Code
66045
Mitscher, L A; Baker, W (1998) Tuberculosis: a search for novel therapy starting with natural products. Med Res Rev 18:363-74
Mitscher, L A; Jung, M; Shankel, D et al. (1997) Chemoprotection: a review of the potential therapeutic antioxidant properties of green tea (Camellia sinensis) and certain of its constituents. Med Res Rev 17:327-65
Gollapudi, S R; Telikepalli, H; Jampani, H B et al. (1994) Alectosarmentin, a new antimicrobial dibenzofuranoid lactol from the lichen, Alectoria sarmentosa. J Nat Prod 57:934-8
Devasthale, P V; Mitscher, L A; Telikepalli, H et al. (1992) Dactylocyclines, novel tetracycline derivatives produced by a Dactylosporangium sp. III. Absolute stereochemistry of the dactylocyclines. J Antibiot (Tokyo) 45:1907-13
Mitscher, L A; Drake, S; Gollapudi, S R et al. (1987) A modern look at folkloric use of anti-infective agents. J Nat Prod 50:1025-40
Mitscher, L A (1987) Chemistry of newer antibiotics directed toward overcoming bacterial resistance. Bull N Y Acad Med 63:269-94
Boger, D L; Yasuda, M; Mitscher, L A et al. (1987) Streptonigrin and lavendamycin partial structures. Probes for the minimum, potent pharmacophore of streptonigrin, lavendamycin, and synthetic quinoline-5,8-diones. J Med Chem 30:1918-28
Mitscher, L A; Drake, S; Gollapudi, S R et al. (1986) Isolation and identification of higher plant agents active in antimutagenic assay systems: Glycyrrhiza glabra. Basic Life Sci 39:153-65
Boger, D L; Mitscher, L A; Mullican, M D et al. (1985) Antimicrobial and cytotoxic properties of 9,10-dihydrophenanthrenes: structure-activity studies on juncusol. J Med Chem 28:1543-7