A5105458378- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Colorectal Cancer Treatments and Studies
- Vanadium and Halogenation Chemistry
- Inflammasome and immune disorders
- Crystallography and molecular interactions
- Metal complexes synthesis and properties
- Metal-Catalyzed Oxygenation Mechanisms
- Free Radicals and Antioxidants
- Cancer Genomics and Diagnostics
- RNA Interference and Gene Delivery
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Genetic factors in colorectal cancer
- Genomics, phytochemicals, and oxidative stress
- Computational Drug Discovery Methods
- Takotsubo Cardiomyopathy and Associated Phenomena
- Gout, Hyperuricemia, Uric Acid
- Pharmacological Effects of Medicinal Plants
- Selenium in Biological Systems
- Pulmonary Hypertension Research and Treatments
- Heart rate and cardiovascular health
- PI3K/AKT/mTOR signaling in cancer
- Ethnobotanical and Medicinal Plants Studies
- PARP inhibition in cancer therapy
University of Turin
2012-2024
IFOM
2013
Candiolo Cancer Institute
2013
Although recent clinical trials of BRAF inhibitor combinations have demonstrated improved efficacy in BRAF-mutant colorectal cancer, emergence acquired resistance limits benefit. Here, we undertook a comprehensive effort to define mechanisms underlying drug with the goal guiding development therapeutic strategies overcome this limitation. We generated broad panel resistant cell line models across seven different clinically relevant combinations. Combinatorial treatments were able abrogate...
Inspired by the recent advancements in understanding binding mode of sulfonylurea-based NLRP3 inhibitors to sensor protein, we developed new replacing central sulfonylurea moiety with different heterocycles. Computational studies evidenced that some designed compounds were able maintain important interaction within NACHT domain target protein similarly most active inhibitors. Among studied compounds, 1,3,4-oxadiazol-2-one derivative 5 (INF200) showed promising results being prevent...
Several factors contribute to ischemia/reperfusion injury (IRI), including activation of the NLRP3 inflammasome and its byproducts, such as interleukin-1β (IL-1β) caspase-1. However, may paradoxically exhibit cardioprotective properties. This study aimed assess protective effects novel inhibitor, INF195, both in vitro ex vivo. To investigate relationship between myocardial IRI, we synthetized a series inhibitors, investigated their putative binding mode via docking studies. Through studies...
Aldo-keto reductase 1C3 (AKR1C3) is an attractive target in drug design for its role resistance to anticancer therapy. Several nonsteroidal anti-inflammatory drugs such as indomethacin are known inhibit AKR1C3 a nonselective manner because of COX-off effects. Here we designed two analogues by proposing bioisosteric connection between the carboxylic acid function and either hydroxyfurazan or hydroxy triazole rings. Both compounds were found selective manner. In particular, derivative highly...
High Brassicaceae consumption reduces the risk of developing several cancer types, probably due to high levels glucosinolates. Extracts from Sinapis nigra L. (S. nigra) and alba alba) have been obtained leaves seeds under different conditions using ethanol/water mixtures because their glucosinolates are well accepted by food industry. The EtOH/H₂O 8:2 mixture gives better yields in glucosinolate amounts ground seeds, mainly, sinalbin S. sinigrin nigra. highest antiproliferative activity both...
Poor prognosis in high-grade gliomas is mainly due to fatal relapse after surgical resection the absence of efficient chemotherapy, which severely hampered by blood–brain barrier. However, leaky blood–brain–tumour barrier forms upon tumour growth and vascularization, allowing targeted nanocarrier-mediated drug delivery. The homotypic targeting ability cell-membrane fragments obtained from cancer cells means that these can be exploited this aim. In experimental work, injectable nanoemulsions,...
Abstract A critical step toward defining tailored therapy in patients with cancer is the identification of genetic interactions that may impair—or boost—the efficacy selected therapeutic approaches. Cell models able to recapitulate combinations aberrations are important find drug–genotype poorly affected by heterogeneous genetics human tumors. In order identify novel pharmacogenomic relationships, we employed an isogenic cell panel reconstructs scenarios. We screened a library 43 compounds...
In the search for new chemical scaffolds able to afford NLRP3 inflammasome inhibitors, we used a pharmacophore-hybridization strategy by combining structure of acrylic acid derivative INF39 with 1-(piperidin-4-yl)1,3-dihydro-2H-benzo[d]imidazole-2-one substructure present in HS203873, recently identified binder. A series differently modulated benzo[d]imidazole-2-one derivatives were designed and synthesised. The obtained compounds screened vitro test their ability inhibit NLRP3-dependent...
Summary With the aim to develop natural preservatives displaying also chemopreventive activity, different Commiphora myrrha (Nees) Engl. extracts were studied. Myrrh essential oils, obtained by steam distillation and microwave‐assisted hydrodistillation, several other extracts, sequential procedures with petroleum ether (PE), ethanol, ethyl acetate butanol, have been screened for their antioxidant ( DPPH · scavenging assay) antiproliferative activity (on both nontumour colon cancer cell...
Vanadium has a good therapeutic potential, as several biological effects, but few side have been demonstrated. Evidence suggests that vanadium compounds could represent new class of non-platinum, metal antitumor agents. In the present study, we aimed to characterize antiproliferative activities fluorescent vanadyl complexes with acetylacetonate derivates bearing asymmetric substitutions on β-dicarbonyl moiety different cell lines. The effects proliferation and cycle modulation in lines were...
Abstract The ability of some 2-alkyl(aryl)-4,6-dimethoxy-1,3,5-triazine derivatives to interfere with production reactive oxygen species (ROS) by human phagocytes was evaluated in an in-vitro cell model. Superoxide anion (O2−.) polymorphonuclear cells (PMNs), challenged the chemotactic agent N-formylmethionyl-leucyl-phenylalanine (FMLP), inhibited a dose-dependent manner all compounds tested, 3, 4 and 5 being statistically most active. Adhesion PMNs vascular endothelial (ECs) is critical...
High Brassicaceae consumption reduces the risk of developing several cancer types, probably due to their glucosinolate amount. Extracts from Sinapis nigra L. and alba have been obtained leaves seeds under different conditions using ethanol/water mixtures because well accepted by food industry. The EtOH/H2O 8:2 mixture gives better yields in amounts grinded seeds, mainly sinalbin S. sinigrin nigra. highest antiproliferative activity both non-tumour tumour cell lines was induced extract. To...
Abstract This work proposes a novel approach by which to consistently classify cysteine sites in proteins terms of their reactivity toward dimethyl fumarate (DMF) and fumarate. Dimethyl fumarate‐based drug products have been approved for use as oral treatments psoriasis relapsing‐remitting multiple sclerosis. The adduction DMF its (re)active metabolites certain residues is thought underlie effects. However, only few receptors these compounds discovered date. Our takes advantage the growing...
Abstract The mutational landscape of cancer genomes displays a complex combination genetic lesions affecting oncogenes and tumor suppressor genes. construction cellular models closely recapitulating cancer-linked alterations is prerequisite to understand their role in progression identify genotype- specific pharmacological responses. To recapitulate point mutations we used homologous recombination ‘knock-in’ nucleotide changes the genome human cells. We focused on following alleles: EGFR...
Inspired by the recent advancements in understanding binding mode of sulfonylurea-based NLRP3 inhibitors to sensor protein, we developed new replacing central sulfonylurea moiety with different heterocycles. Computational studies evidenced that some designed compounds were able maintain important interaction within NACHT domain target protein similarly most active inhibitors. Among studied compounds, 1,3,4-oxadiazol-2-one derivative 5 (INF200) showed promising results being prevent...