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As extension of previous studies on polycyclic planar systems which synthetic approach and antiproliferative activity against leukemic cells (FLC, DRTL) were reported, now we became interested to test their antireplicative activity against human immunodeficiency virus since the incorporation of the pyrrole moiety has already led to several classes of non nucleoside reverse transcriptase inhibitors. For this purpose new and non new derivatives of the planar system pyrrolo[1,2-f]phenanthridine and their “non-rigid analogues” were chosen as model framework reaching in total to more than forty compounds variously functionalized. The need for the search of new anti-HIV agent is still pursued because of the increasing spread of the disease in spite of several prevention campaigns, and because of the rapid appearance of drug resistant viral strains which limits drug effectiveness. Among the current anti-HIV agents the reverse transcriptase inhibitors the Nevirapine and TIBO have an important clinical role. It is suggested that they interact with an allosteric site of the enzyme assuming a “butterfly conformation.” This type of conformation is proposed in our “non-rigid” analogue derivatives tested. Molecular modelling studies by using some physico-chemical descriptors (molecular volume, accessible surface area) evidenced good similarities when compared with planar derivatives and highly described substituted pyrroles and were found in good agreement with the docking studies performed by Ding et al, which proposed a receptor having a “butterfly shape region”. At the same time, the superimposition in the conformation of the minimum of energy between Nevirapine, some selected planar compounds and the corresponding non-rigid analogues showed a good geometric fit between the structures (RMS in the range 0.0270-0.0455). These data suggest that a lot of our derivatives could fit favourably in the same binding pocket. Biological screenings evidenced that only few derivatives showed a moderate selectivity against HIV-1, suggesting that even planar molecules having suitable size can inhibit virus replication probably interacting with the same receptor. Moreover, an interesting biological new data has emerged: a planar derivative showed unique properties being able not only to reduce the virus-induced cyto-pathogenecity, but also to stimulate the growth (20-35%) of the same lymphocytes. Considering that the stimulation of the lymphocytes cells can be a crucial factor in anti-AIDS therapy, this class of compounds can be considered for further developments of new candidates which join anti-AIDS and immuno-stimulant activity.

A set of variously substituted 1-arylpyrazol-3-one derivatives, including the di-ortho-aryl substituted ones, was synthesized as new potential anticancer compounds. To fulfill this aim, herein a regiospecific synthesis was proposed utilizing a new revisited one pot procedure, starting from commercial anilines and easily accessible 2,5-dimethyl-furan-3-one. In the course of the sequential ordered steps, in some cases, a nitro group displacement by chlorine took place to a minor extent. The in vitro screening against the full panel of ~60 human cancer cell lines (NCI) showed a moderate, but promising selective antiproliferative activity against the UO31 renal tumor cell line, only in compounds with the introduction on the phenyl moiety of a -CF3 or two Cl groups.

The X-ray emission of the young Sun was much harder and intense than today and might have played a significant role in the evolution of complex organics in protoplanetary environments. We investigate the effects of soft X-rays on tryptophan molecules in aqueous solutions at room temperature. As results of the irradiation experiments we detect several light species indicative of fragmentation, together with large molecular structures such as tryptophan dipeptide and tripeptide. Complexification is more evident in H2O solution than in D2O, probably due to isotopic effects. The abundances of peptides depend on the irradiation dose and decrease with increasing energy deposition. Radicals such as D, OD, H and OH, induced by the X-ray interaction with solvents, play a major role in determining the final products.

The IKK kinases family represents a thrilling area of research because of its importance in regulating the activity of NF-kB transcription factors. The discovery of the central role played by IKK-β in the activation of transcription in response to apoptotic or inflammatory stimuli allowed to considerate its modulation as a promising tool for the treatment of chronic inflammation and cancer. To date, several IKK-β inhibitors have been discovered and tested. In this work, an analysis of the interactions between different classes of inhibitors and their biological target was performed, through the application of Molecular Docking and Pharmacophore/3D-QSAR approaches to a set of 141 inhibitors included in the Binding Database. In order to overcome the difficulty due to the lack of crystallographic data for IKK-β, a homology model of this protein has been built and validated. The results allowed to study in depth the structural bases for the interaction of each family of inhibitors and provided clues for further modifications, with the aim of improving the activity and selectivity of designed drugs targeting this enzyme.

New 1,3,4-substituted pyrrolo[3,2-c]quinoline derivatives were synthesised in good yields by oxidative heteroannulation of internal imines starting from easily prepared substituted 5-(2-aminophenyl)pyrroles and commercially available aryl and heteroaryl aldehydes. The reaction occurs as a one-pot process involving an intramolecular acid catalysed reaction.