Oleocanthal is one of the phenolic compounds of extra virgin olive oil with important anti-inflammatory properties. Although its potential anticancer activity has been reported, only limited evidence has been provided in cutaneous malignant melanoma. The present study is aimed at investigating the selective in vitro antiproliferative activity of oleocanthal against human malignant melanoma cells. Since oleocanthal is not commercially available, it was obtained as a pure standard by direct extraction and purification from extra virgin olive oil. Cell viability experiments carried out by WST-1 assay demonstrated that oleocanthal had a remarkable and selective activity for human melanoma cells versus normal dermal fibroblasts with IC50s in the low micromolar range of concentrations. Such an effect was paralleled by a significant inhibition of ERK1/2 and AKT phosphorylation and downregulation of Bcl-2 expression. These findings may suggest that extra virgin olive oil phenolic extract enriched in oleocanthal deserves further investigation in skin cancer.

Endocannabinoids (ECs) are signalling lipids which exert their actions by activation cannabinoid receptor type-1 (CB1) and type-2 (CB2). These receptors are involved in many physiological and pathological processes in the central nervous system (CNS) and in the periphery. Despite many potent and selective receptor ligands have been generated over the last two decades, this class of compounds achieved only a very limited therapeutic success, mainly because of the CB1-mediated side effects. The endocannabinoid system (ECS) offers several therapeutic opportunities beyond the direct activation of cannabinoid receptors. The modulation of EC levels in vivo represents an interesting therapeutic perspective for several CNS-related diseases. The main hydrolytic enzymes are fatty acid amide hydrolase (FAAH) for anandamide (AEA) and monoacylglycerol lipase (MAGL) and ,-hydrolase domain-6 (ABHD6) and -12 (ABHD12) for 2-arachidonoyl glycerol (2-AG). EC metabolism is also regulated by COX-2 activity which generates oxygenated-products of AEA and 2-AG, named prostamides and prostaglandin-glycerol esters, respectively. Based on the literature and patent literature this review provides an overview of the different classes of inhibitors for FAAH, MAGL, ABHDs and COX-2 used as tool compounds and for clinical development with a special focus on CNS-related diseases.

The CB2 receptor is a therapeutic target of increasing importance for several diseases, including pain, inflammation, neurodegeneration, cancer and osteoporosis. While several compounds showing CB2-selective agonist or inverse agonist properties have been developed, only few CB2 receptor selective neutral antagonists are actually known. Such type of compounds could be useful to study more in depth the role of the CB2 receptor, because they lack the ability to counteract its "constitutive" activity. Here we describe the synthesis and biological activity of a series of biphenylic carboxamides as a new class of CB2 receptor selective ligands. In binding assays, one of these compounds showed good CB2 receptor affinity and selectivity (Ki = 11.48 nM; Selectivity Index = 130). Furthermore, in functional assays, the same compound showed a very interesting pharmacological profile as CB2 receptor selective neutral antagonist. These results pave the way to further developments, including structural optimization, with the aim to obtain more potent CB2 receptor ligands with this peculiar feature.

(1) Background: Neutropenic enterocolitis (NEC) is a life-threatening complication following chemotherapy with high mortality rates. Early diagnosis is crucial to improve outcomes. We designed a large prospective study employing bedside ultrasonography (US) as a novel approach to allow early diagnosis and prompt treatment to reduce mortality. (2) Methods: NEC was defined as US or computed tomography (CT)-proven bowel wall thickness ≥ 4 mm at the onset of at least one of the following symptoms: fever and/or abdominal pain and/or diarrhea during neutropenia. From 2007 to 2018, 1754 consecutive patients underwent baseline bedside US that was invariably repeated within 12 h from the onset of symptom(s) suggestive of NEC. (3) Results: Overall, 117 episodes of NEC were observed, and overall mortality was 9.4%. Bowel wall thickening was invariably absent in the negative control group. Abdominal pain associated with one or more symptoms correlated with the highest relative risk (17.33), sensitivity (89.7%), specificity (100%), and accuracy (96.2%) for diagnosis. The combination of abdominal pain and fever at onset significantly correlated with worse survival (p < 0.0001, OR 13.85). BWT (p = 0.046), type of therapy (p = 0.049) and blood culture positivity (p = 0.003) correlated with worse survival. (4) Conclusions: Bedside ultrasound is a non-invasive and radiation free imaging technique for early diagnosis of NEC and its prompt treatment significantly reduced mortality.

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