Investigations into the Mechanism of Action and Antifungal Activitiy of the Botanical Coumarin Surangin B
Year: 2004
Type: dissertation
Abstract: The mechanism of action of surangin B, a coumarin from the roots of Mammea longifolia, was examined in bovine heart mitochondria and mouse brain synaptosomal preparations. The potential antifungal activity of surangin B was also investigated. Complexes 11, I11 and IV of bovine heart mitochondria were strongly inhibited by surangin By but complex I was insensitive to this compound. Analysis of surangin B's inhibition of complex I1 used submitochondrial particles. Surangin B displayed noncompetitive kinetics when either succinate or decylubiquinone were used as substrates. indicating that it binds to a site which is distinct from both the succinate binding site and the domain responsible for interacting with ubiquinone. Difference spectra of reduced complex I11 equilibrated with surangin B closely parallelled those of antimycin A, but were very different to those of the selective Q, site inhibitors myxothiazol and famoxadone. Other experiments used the electron acceptor 2-nitrosofluorene, which intercepts electrons specifically from the Qi site. These experiments confirmed that like antimycin A, surangin B selectively blocks electron diversion to 2-nitrosofluorene through Qi within complex 111. Surangin B causes presynaptic release of both neurotransmitter and nonneurotransmitter amino acids from mouse brain synaptosomes. The stimulatory effect of surangin B and other complex 111-specific inhibitors on amino acid release was inhibited by N,N,N1,N'-tetramethyl-p-phenylenediamine suggesting that complex I11 blockade in mitochondria of the nerve ending is an important mechanism causing release. Surangin B also inhibited in vitro mycelial growth and spore germination in several species of fungi. As an inhibitor of mycelial growth surangin B showed strongest activity against Rhizoctonia solani (ICSo = 3.8 pM) and Botrytis cinerea (IC50 =11.2 pM), but inhibitory effects were less pronounced in Alternaria dauci, Fusarium oxysporum and Penicillium sp. (IC50s > 30 pM) and absent in Trichoderma harzianum. Surangin B reduced the level of spore germination in Fusarium oxysporum (IC5o = 2.3 pM) and Botrytis cinerea (IC50 = 1.4 pM), although Alternaria dauci was considerably more tolerant of this coumarin (IC5o = 500 pM). The activity of surangin B compared favorably with certain commercial fungicides indicating that coumarins of this type may have potential as an antifungal agents.
Source: Summit (Simon Fraser University)
Author: Yanshen Deng
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2171308896