66166-59-4Relevant academic research and scientific papers
First synthesis of parazoanthine-A and its O-Me derivative
Manzo, Emiliano,Pagano, Dario,Nuzzo, Genoveffa,Gavagnin, Margherita,Ciavatta, Maria Letizia
, p. 7083 - 7084 (2012)
Parazoanthine A (7.0% overall yield) and its O-methyl derivative (6.2% overall yield) were prepared by a concise biomimetic synthesis based on the coupling reaction of l-arginine methyl ester dihydrochloride with isocyanate derivatives of p-coumaric acid and 4-methoxy-cinnamic acid, respectively. The synthetic approach is designed to obtain a wider class of parazoanthine analogs.
Identification of the hydantoin alkaloids parazoanthines as novel CXCR4 antagonists by computational and in vitro functional characterization
Vitale, Rosa Maria,Thellung, Stefano,Tinto, Francesco,Solari, Agnese,Gatti, Monica,Nuzzo, Genoveffa,Ioannou, Efstathia,Roussis, Vassilios,Ciavatta, Maria Letizia,Manzo, Emiliano,Florio, Tullio,Amodeo, Pietro
supporting information, (2020/10/29)
CXCR4 chemokine receptor represents an attractive pharmacological target due to its key role in cancer metastasis and inflammatory diseases. Starting from our previously-developed pharmacophoric model, we applied a combined computational and experimental approach that led to the identification of the hydantoin alkaloids parazoanthines, isolated from the Mediterranean Sea anemone Parazoanthus axinellae, as novel CXCR4 antagonists. Parazoanthine analogues were then synthesized to evaluate the contribution of functional groups to the overall activity. Within the panel of synthesized natural and non-natural parazoanthines, parazoanthine-B was identified as the most potent CXCR4 antagonist with an IC50 value of 9.3 nM, even though all the investigated compounds were able to antagonize in vitro the down-stream effects of CXC12, albeit with variable potency and efficacy. The results of our study strongly support this class of small molecules as potent CXCR4 antagonists in tumoral pathologies characterized by an overexpression of this receptor. Furthermore, their structure–activity relationships allowed the optimization of our pharmacophoric model, useful for large-scale in silico screening.
