ABSTRACT
Systemic mycoses are fungal diseases attacking the body through an internal organ. They are the cause of increasing morbidity rates, especially among the immunocompromised population (e.g. with HIV), but also exist as a co-infection in patients with COVID-19. Nowadays, the 'life-saving/last chance' drug (and a poison to humans), Amphotericin B (AmB), is the representative of nonaromatic heptaene macrolides. However, previously obtained data indicate significantly higher antifungal activity of the aromatic heptaene subgroup (AHM), which is unfortunately correlated with their high mammalian toxicity. The undertaken studies concern Partricin and Candicidin complexes as the main representatives of AHMs. Three aromatic heptaene macrolides: Partricin A, Partricin B and Candicidin D were isolated from fermentation broths of S. aureofaciens and S. griseus, respectively, by initial purification, followed by selected chromatographic techniques such as centrifugal partitioning chromatography (CPC) and prep-HPLC. Later on, they were subjected to controlled chromophore geometry change (cis-trans to all-trans) via photochemical isomerization, using UV light of k = 365 nm. The obtained all-trans isomers, regarded as aromatic analogues of AmB, were tested for in vitro selective toxicity indexes (STIs) towards C. albicans cells versus human erythrocyte model. Due to the diminished hemotoxicity of the all-trans isomers - which were maintaining most of their fungicidal power - the obtained STIs were very promising and far better than for AmB (previously published in: J.Górska et al. (2021) Int. J. Mol. Sci. 22). Hence, the all-trans AHMs bear a great potential to be weaponized on the antifungal battlefield. Nevertheless, since individual AHMs are commercially unavailable and difficult to obtain due to their complex nature, our studies will focus on facilitation of the isolation process and further improvement of their STIs, mainly through rational, structural modifications.
ABSTRACT
A comparative phytochemical study on the phenylethanoid glycoside (PhEG) composition of the underground organs of three Plantago species (P. lanceolata, P. major, and P. media) and that of the fruit wall and seed parts of Forsythia suspensa and F. europaea fruits was performed. The leaves of these Forsythia species and six cultivars of the hybrid F. × intermedia were also analyzed, demonstrating the tissue-specific accumulation and decomposition of PhEGs. Our analyses confirmed the significance of selected tissues as new and abundant sources of these valuable natural compounds. The optimized heat treatment of tissues containing high amounts of the PhEG plantamajoside (PM) or forsythoside A (FA), which was performed in distilled water, resulted in their characteristic isomerizations. In addition to PM and FA, high amounts of the isomerization products could also be isolated after heat treatment. The isomerization mechanisms were elucidated by molecular modeling, and the structures of PhEGs were identified by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectrometry (HR-MS) techniques, also confirming the possibility of discriminating regioisomeric PhEGs by tandem MS. The PhEGs showed no cytostatic activity in non-human primate Vero E6 cells, supporting their safe use as natural medicines and allowing their antiviral potency to be tested.