Nature's gifts have been used by mankind since ancient times, from the Amazon poisons used by natives up to more modern phytochemical based drugs. The use of medicinal plants represents a good source of novel natural therapeutic drugs and for the improvement of pharmacophore moieties in medicinal chemistry. Pharmacologically active substances can be obtained from natural sources such as plants, marine organisms and insects. Indeed, common intermediates coming from the metabolism of distant kingdoms often show a wider variety of biological activities also thanks to the ability to interact and ¿communicate¿ with different biological systems. An example is represented by iridoids, a central bridge between plant and animal kingdom. These compounds, synthesized both in plants and insects, are a key tool for intra-species and inter-kingdom communication and their functions and biological activities are strongly connected. Another biochemical bridging point between two distant worlds such as terrestrial and marine organisms is represented by sulfur-containing compounds. This project is aimed to identify and characterize key intermediates of the organic sulfur metabolism and unique sulfur biological compounds obtained by prokaryotes, plant and animal kingdoms with potential therapeutic activity. A metabolomics-based approach coupled with advanced analytical methods, i.e. chromatographic, spectroscopic and spectrometric methods, will be performed. In-vitro and in-vivo experiments in different biological models will be performed for the evaluation of the role of sulfur-containing compounds in physiological and pathological conditions. Sulfur metabolism will be furthermore investigated in terrestrial and marine organisms in relation to nitrogen and carbon (e.g. amines, amino acids and keto acids) in order to provide a more complete scenario and shed light on sulfur biochemical cycle
My research at Sapienza University of Rome has led to high impact published results. It was focused on organic natural compounds and on the modulation of oxidative stress in biological and pathological processes such as inflammation and neurodegeneration. During this period we investigated the stability and the antiviral activity of the natural antioxidant Resveratrol developing a novel bioactive formulation with a natural biopolymer that was patented by my former research group from Sapienza University of Rome (EP2674155B1). During this last year the research field on natural products led me to identify and determine an interesting class of common metabolites belonging to extremely distant species such as terrestrial and marine organisms, the class of sulfur-containing compounds. These chemical "meeting points" aroused my curiosity on the origin of life and on the role of marine ancestral sulfurous compounds in higher organisms due to their evolutionary conservation.
The aim of this project will be to elucidate the structure of novel natural active products such as sulfur-containing compounds and to study their biosynthetic pathways in distant species.
The scientific research on the chemical evolution and the biochemistry of organic sulfur is an essential field of research that can be defined still "virgin" from a scientific point of view with respect to the knowledge acquired on the biochemistry of other chemical elements of "life" such as carbon, oxygen and nitrogen. In the current scientific context of biochemistry it is extremely important to deepen and better understand the role of organic sulfur in the metabolism of different species given the emerging role that this element covers in primary and fundamental functions of living beings.
This grant will help me to combine the two research interests described above to advance a new fertile research strategy on the chemical evolution of metabolism and sulfur biochemical cycle.