Sangermano, Felicia (2021) MICROBIAL BIOACTIVE METABOLITES FOR AGRICULTURE AND PHARMACEUTICAL INDUSTRY. [Tesi di dottorato]

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As the human population continues to grow, more and more crops are needed to meet this growing demand. This has increased the use of pesticides and herbicides causing damage to both the environment and human health. For this reason, industries are increasingly active in seeking viable alternatives that are safe and can minimize the environmental impact. Bioactive metabolites produced by plants and microorganisms are an excellent biodegradable alternative to satisfy these requests; preserving agrarian production and environmental heritage. Natural products are considered a major source of new bioactive agents. Fungi and plant-derived natural products are also an excellent source of pharmaceuticals, cosmeceuticals and nutraceuticals. They are appreciated for their immunostimulant, antimicrobial, antibiotic, anti-oxidative and anti-cancer properties. During my PhD, I focused on isolating and characterizing metabolites extracted from fungi. I then studied their biological activity and tested their toxicity using in vivo and in vitro assays. The result was the discovery of new fungal metabolites to be used as bioherbicides against particular types of weeds. In particular, radicinin isolated from Cochliobolus australiensis, was found to be effective in the management of buffelgrass (Cenchrus ciliaris), a perennial C4 bunchgrass that becomes invasive. I demonstrated the absence of radicinin toxicity on zebrafish embryonic development, a useful fish model to study toxicity. I also studied the activity of two diterpenoid α-pyrones, named higginsianins A and B, isolated from Colletotrichum higginsianum that showed interesting cytotoxic activity against tumor cells. These metabolites can induce DNA damage and cell cycle arrest. In the last part of my PhD training I performed toxicological studies on ten natural compounds extracted from plants and fungi with potential application as bioherbicides and biopesticides. I found that cyclopaldic acid among them is embryotoxic and exhibits selective toxicity against transformed murine fibroblasts. Further investigations will be required to assess its potential application in the anticancer field.

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