Ricerc@Sapienza

Introduction: Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies (representing 15–40% of fatal TC cases), classified as stage IV by the American Joint Committee on Cancer, regardless of tumor size or presence of lymph node and distant metastases. A large number of genetic alterations are associated with ATC, especially causing dysfunctions in the ERK1/2-MEK1/2 and PI3K-AKT signaling pathways (BRAF, p53, RAS, EGFR, VEGFR1, VEGFR2, chromosomal rearrangements, etc). New drugs targeting these molecular pathways have recently been evaluated in ATC.

Phosphodiesterases (PDEs) regulate the intracellular levels of cAMP and cGMP. The great clinical success of the PDE5 inhibitors, Sildenafil (Viagra), Vardenafil (Levitra) and Tadalafil (Cialis) has led to an increasing interest for this class of enzymes. Recent studies have shown a correlation between tumor growth and PDE5 overexpression, making PDE5-selective inhibitors promising candidates for cancer treatment. The search for such inhibitors rests today on radioactive assays.

The structural characterization of the lipopolysaccharide (LPS) from extremophiles has
important implications in several biomedical and therapeutic applications. The polyextremophile
Gram-negative bacterium Halobacteroides lacunaris TB21, isolated from one of the most extreme
habitats on our planet, the deep-sea hypersaline anoxic basin Thetis, represents a fascinating
microorganism to investigate in terms of its LPS component. Here we report the elucidation of

The stability of lycopene in two vegetable oils, sunflower seed oil (SSO) and grape seed oil (GSO), was investigated by analyzing the carotenoid degradation kinetics in the temperature range of 10–40°C. A tomato oleoresin containing 6% (w/w) of lycopene was used to prepare lycopene-enriched oil samples. Analysis of kinetic data showed that lycopene degradation follows first-order kinetics, with an apparent activation energy of 70.7 kJ mol–1 in SSO and 69 kJ mol–1 in GSO. The estimated half-life of lycopene was found to depend on oil type and storage temperature.

We discovered a series of azole antifungal compounds as effective antiprotozoal agents. They displayed promising inhibitory activities within the micromolar-submicromolar range against P. falciparum, L. donovani, and T. b. rhodesiense. Moreover, most of such compounds showed excellent nanomolar IC50against T. cruzi, showing also very low cytotoxicity. Discussion of structure-activity relationships and biological data for these compounds are provided against the different parasites. To assess the mechanism of action against T.

Aberrant activation of the Hedgehog (Hh) pathway is responsible for the onset and progression of several malignancies. Small molecules able to block the pathway at the upstream receptor Smoothened (Smo) or the downstream effector Gli1 have thus emerged recently as valuable anticancer agents. Here, we have designed, synthesized, and tested new Hh inhibitors taking advantage by the highly versatile and privileged isoflavone scaffold. The introduction of specific substitutions on the isoflavone's ring B allowed the identification of molecules targeting preferentially Smo or Gli1.