A5011872889- Axon Guidance and Neuronal Signaling
- Chromatography in Natural Products
- Apelin-related biomedical research
- Computational Drug Discovery Methods
- Flavonoids in Medical Research
- Angiogenesis and VEGF in Cancer
- Protein Tyrosine Phosphatases
- Free Radicals and Antioxidants
- Natural product bioactivities and synthesis
- Click Chemistry and Applications
- Plant-based Medicinal Research
- Nerve injury and regeneration
- Nuclear Receptors and Signaling
- HER2/EGFR in Cancer Research
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Bioactive Compounds in Plants
University of Parma
2012-2015
The Eph receptor-ephrin system is an emerging target for the development of novel antiangiogenetic agents. We recently identified lithocholic acid (LCA) as a small molecule able to block EphA2-dependent signals in cancer cells, suggesting that its (5β)-cholan-24-oic scaffold can be used template design new generation improved EphA2 antagonists. Here, we report and synthesis extended set LCA derivatives obtained by conjugation carboxyl group with different α-amino acids. Structure-activity...
The Eph receptor tyrosine kinases and their ephrin ligands are key players in tumorigenesis many reports have correlated changes expression with a poor clinical prognosis solid tumours. Agents targeting the Eph-ephrin system might emerge as new tools useful for inhibition of different components cancer progression. Even if classes small molecules interactions been reported, use is hampered by chemical stability low potency. Stable potent crucial to achieve robust pharmacological...
The Eph-ephrin system comprises emerging proteins involved in many pathophysiological processes. pharmacological activity of the main metabolites derived from intake some classes (poly)phenolic compounds, such as caffeoylquinic acids, flavan-3-ols, and ellagitannins, on interaction was evaluated at physiological concentrations. Functional studies to elucidate their role prostate cancer were also performed.Among 21 phenolics screened by an ELISA-binding assay, just urolithin C, D, ellagic...
The Eph-ephrin system, including the EphA2 receptor and ephrinA1 ligand, plays a critical role in tumor vascular functions during carcinogenesis. We previously identified (3α,5β)-3-hydroxycholan-24-oic acid (lithocholic acid) as an antagonist that is able to inhibit activation; it therefore potentially useful novel receptor-targeting agent. Herein we explore structure-activity relationships of focused set lithocholic derivatives based on molecular modeling investigations displacement binding...
Abstract Lithocholic acid (LCA), a physiological ligand for the nuclear receptor FXR and G‐protein‐coupled TGR5, has been recently described as an antagonist of EphA2 receptor, key member ephrin signalling system involved in tumour growth. Given ability LCA to recognize FXR, receptors, we hypothesized that structural requirements small molecule bind each these receptors might be similar. We therefore selected set commercially available or TGR5 ligands tested them their inhibit by targeting...
The Eph–ephrin system plays a critical role in tumor growth and vascular functions during carcinogenesis. We had previously identified cholanic acid as competitive reversible EphA2 antagonist able to disrupt EphA2-ephrinA1 interaction inhibit activation prostate cancer cells. Herein, we report the synthesis biological evaluation of set derivatives obtained by conjugation its carboxyl group with panel naturally occurring amino acids aim improve receptor inhibition. Structure-activity...
The EPH receptor A2 (EPHA2) represents an attractive anticancer target. With the aim to identify novel EPHA2 antagonists, a virtual screening campaign, combining shape-similarity and docking calculations, was conducted on set of commercially available compounds. A combined score, taking into account both ligand- structure-based results, then used most promising candidates. Two compounds, selected among best-ranked ones, were identified as antagonists with micromolar affinity.