Discovery of antifungal and antibacterial volatile natural products and synthetic drug analogs

Abstract

The discovery of antibiotics is considered as one of the great revolutions in the history of medication. This group of drugs is focusing on controlling infectious diseases and is indeed beneficial to the health of human being and animal. However, overdosing this form of medicines resulted in the development of antibiotic resistance which turned into a serious global health issue nowadays. The demand of fresh new leads for antimicrobial agents is still severely large. Therefore, the aim of my study is to search interesting molecules with antibiotic properties, either from nature, like fungal volatile organic compounds, or digging into the existed synthetic drugs, for example linezolid and tedizolid derivatives. The closed-loop stripping apparatus (CLSA) headspace technique was used into the extraction of the volatile organic compounds released from endophytic fungi Geniculosporium sp. and Xylariaceae, respectively. The extracts were detected and characterized via GC-MS based on their mass spectra and retention indices in comparison to literature data and commercially available or synthetic reference compounds. The drawbacks of this methodology are the incomplete digital data base and highly similar isomers. On the other hand, an in silico-study provided several new and promising lead compounds related to linezolid. Thus, the total synthesis was planned and conducted. Besides, several tedizolid derivatives were also obtained via synthesis. At last, bioassay of authentic synthetic samples and natural products was evaluated against a panel of common fungal and bacterial microorganisms. Interestingly, some fungal volatiles exhibited a moderate antifungal and antibacterial activity, whilst the synthetic drug analogs displayed yet no significant antimicrobial effect as expected.