Abstract
The exceptional diversity of the genus Rhododendron has a strong potential for identification, characterization, and production of bioactive lead compounds for health purposes. A particularly relevant field of application is the search for new antibiotics. Here, we present a comparative analysis of nearly 90 Rhododendron species targeted toward the search for such candidate substances. Through a combination of phytochemical profiles with antimicrobial susceptibility and cytotoxicity, complemented by phylogenetic analyses, we identify seven potentially antimicrobial active but non-cytotoxic compounds in terms of mass-to-charge ratios and retention times. Exemplary bioactivity-guided fractionation for a promising Rhododendron species experimentally supports in fact one of these candidate lead compounds. By combining categorical correlation analysis with Boolean operations, we have been able to investigate the origin of bioactive effects in further detail. Intriguingly, we discovered clear indications of systems effects (synergistic interactions and functional redundancies of compounds) in the manifestation of antimicrobial activities in this plant genus.
Highlights
The World Health Organization declared antibiotic resistance a public health emergency of yet unknown proportions (WHO, 2011)
To assess the exceptional diversity of the genus Rhododendron, a combined phylogeny based on three DNA regions, trnK, trnLF, and ITS, was constructed
Thereby, Bayesian inference and Maximum Likelihood analyses resulted in phylogenetic trees of the genus Rhododendron with the same topology (Figure 2)
Summary
The World Health Organization declared antibiotic resistance a public health emergency of yet unknown proportions (WHO, 2011). Emerging resistance of pathogens to treatment with antibiotics is responsible for >30,000 deaths per year in the European Union alone, with worldwide incidences predicted to be orders of magnitude higher. In excess of 300,000 different plant species have so far been cataloged by botanists around the globe (Angiosperm Phylogeny Group, 2016), and 25% of Bioactivity in Rhododendron all commercial pharmaceutical drugs are based on plant natural products (Cragg et al, 1997; Cragg and Newman, 2013). Plants offer an immense resource of chemical diversity to be exploited in pharmaceutical research and drug discovery, in particular in the search for novel antibiotics (Harvey et al, 2015)
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