Ismail, Shurooq (2023) Exploitation of synergistic effects between plant-derived compounds and antimicrobial peptides for biotechnological purposes. [Tesi di dottorato]

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Abstract

The discovery of penicillin by Sir Alexander Fleming in 1928 started the golden age of natural product antibiotic discovery that peaked in the mid-1950s. Since then, a gradual decline in antibiotic discovery as well as the development and evolution of drug resistance in many human pathogens has led to the current antimicrobial resistance crisis. Plants are one of the dominant creatures on earth and represent the primitive rich source of antimicrobial natural products. Indeed, plants adapt and encounter diverse environmental challenges since their existence. For this reason, they have evolved sophisticated and effective defense mechanisms against predators, abiotic stress, and diseases. Due to this adaptive process, plants can produce a massive chemical arsenal of secondary metabolites effective in combating even the most dangerous infections. Here, a bio-guided purification of Centaurea hyalolepis and Ephedra foeminea extracts were performed for the first time to identify bioactive compounds. The molecular structure of the identified compounds was determined by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) analyses. Six compounds were isolated and identified from E. foeminea extracts including both monoterpenoid phenols carvacrol and thymol, in addition to four acylated kaempferol glycosides. Regarding C. hyalolepis extracts, three sesquiterpene lactones were isolated and identified as cnicin, 11β,13-dihydrosalonitenolide and salonitenolide. Among the identified compounds,kaempferol-3-O-α-L-(2”,4”-di-E-p-coumaroyl)-rhamnopyranoside which was found to be endowed with pronounced antibacterial properties and significant anti-biofilm activity against S. aureus bacterial strains. Moreover, significant additive effects were observed when this compound was tested in combination with r(P)ApoBLPro peptide against the tested S. aureus MRSA WKZ-2 and A. baumannii ATCC 17878 bacterial strains. Preliminary experiments were also performed to load this compound on hydroxyethyl cellulose (HEC) films cross-linked with citric acid, thus developing an active food packaging system that might be able to prevent food spoilage. Altogether, the achieved results open interesting perspectives to the applicability of the identified plant-derived compounds in several fields, such as biomedical, pharmaceutical, cosmeceutical, as well as in food preservation and active packaging areas.

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