عنوان

Investigation of higher plants for potential antiinfective agents:

Number

TLpq304223800

.Language of Text, Soundtrack etc

انگلیسی

Title Proper

Investigation of higher plants for potential antiinfective agents:

General Material Designation

[Thesis]

First Statement of Responsibility

D. M. Hatch

Title Proper by Another Author

Part I. Isolation and antimicrobial activity of fusaric acid and dehydrofusaric acid from Fusarium oxysporum and Part II. Isolation and structure elucidation of components of Baphia nitida Lodd and Part III. Evaluation of higher plant constituents in a novel assay for the potential inhibition of phenoloxidase in Cryptococcus neoformans

Subsequent Statement of Responsibility

A. M. Clark

Name of Publisher, Distributor, etc.

The University of Mississippi

Date of Publication, Distribution, etc.

1995

Specific Material Designation and Extent of Item

109

Dissertation or thesis details and type of degree

Ph.D.

Body granting the degree

The University of Mississippi

Text preceding or following the note

1995

Text of Note

The primary goal of this research project was the exploration of plant and microbial sources for new prototype antibiotics, including compounds that could inhibit the production and/or function of an important virulence factor in Cryptococcus neoformans. Plant and fungal sources were investigated for new agents. Plant sources included the collection by collaborators in others countries of plants not previously evaluated for antimicrobial activity. Fusarium oxysporum was found growing on an isolate obtained from a lichen. The ethyl acetate extract of this fungus, grown in broth culture, was found to have anticandidal, antibacterial, and antimycobacterial activity. Fractionation of the extract led to isolation of dehydrofusaric acid and fusaric acid. The antimicrobial activity of fusaric acid is significant for Candida albicans, Aspergillus flavus, Aspergillus fumigatus, Staphylococcus aureus, Bacillus subtilis, and Trichophyton mentagraphytes. To our knowledge the only previously reported activity for fusaric acid is against Bacillus subtilis, Escherichia coli and Ustilago zeae (59, 58). Toxicity of fusaric acid against Vero cells is TC{50} 10-15 mug/ml. Dehydrofusaric acid has antimicrobial activity against B. subtilis (5 mm zone, MIC > 50 mug/ml). No previous antibacterial activity has been reported for dehydrofusaric acid. Dehydrofusaric acid is not cytotoxic to Vero cells. Baphia nitida has been used extensively in Africa and specifically in Nigeria as a folkloric remedy for a number of ailments, ranging from female infertility to skin infections. Based on this, its antifungal activity was evaluated and an attempt was made to isolate active compounds by means of bioassay-directed fractionation. Although the antifungal activity of the crude extract and some of the initial fractions was good to marginal (maximum zone of 6 mm against a given organism), none of the pure compounds isolated were significantly active against any organism. Four pure compounds were isolated: sophoradiol, soyasapogenol B, sitosterol and its glucoside. This is the first report of the occurrence of these compounds in Baphia nitida. usd\betausd-sitosterol-glucoside and sophoradiol had slight antifungal activity. Phenoloxidase is a known virulence factor in Cryptococcus neoformans and its inhibition renders the organism less virulent. An assay to evaluate the potential inhibition of phenoloxidase in C. neoformans was established. Randomly selected plant extracts (66) and pure compounds (150) were screened for in vitro inhibition of melanin production in Cryptococcus neoformans, as potential leads to inhibition of phenoloxidase. Of the 66 plants screened, 10 showed significant inhibitions (albino zones greater than 3 mm) and 10 of the pure compounds showed significant activity. The general antioxidants, usd\betausd-carotene, Vitamin E and Vitamin C, did not show activity. Diethyldithiocarbamic acid was found to inhibit melanin production in Cryptococcus neoformans without having any significant fungicidal activity and was therefore used as a positive control.

Pharmacology

Pure sciences

A. M. Clark

D. M. Hatch

Electronic name

p

[Thesis]

276903

a

Y