Daniele Giallombardo

Aza-isoindolo and isoindolo-azaquinoxaline derivatives with antiproliferative activity

Three new ring systems, pyrido[2,3:3,4]pyrrolo[1,2-a]quinoxalines, pyrido[3,2:3,4]pyrrolo[1,2-a]quinoxalines and pyrido[2,3:5,6]pyrazino[2,1-a]isoindoles, were synthesized through an aza-substitution on the already active isoindolo-quinoxaline system and in particular in the position 7 or 4 of the isoindole moiety and in position 5 of the quinoxaline portion. All new compounds were screened by the National Cancer Institute (Bethesda, MD) against a panel of 60 human tumor cell lines. Biological results of the most active derivatives, with pGI50 values between 7.09 and 7.27, confirmed the importance of the presence of methoxy substituents for biological activity. The anti-proliferative effect of selected quinoxalines was associated with apoptosis of the cells and arrest in G2/M phase of the cell cycle. DNA binding properties of the compounds was also assessed to investigate the possible mechanism of action.

Synthesis of a fluorinated graphene oxide–silica nanohybrid: improving oxygen affinity

An easy method to achieve a fluorinated graphene oxide–silica nanohybrid (GOSF) is presented. Graphene oxide (GO) was synthesized by Hummers modified method, the GO–silica nanohybrid (GOS) was obtained via Fischer esterification, the fluorinated moiety (3-pentadecafluoroheptyl-5-perfluorophenyl-1,2,4-oxadiazole) was introduced by nucleophilic substitution operated by the hydroxyl functionalities onto the GOS surface. Full characterization of the new materials confirmed the formation of covalent bonds between the graphene oxide/silica hybrid matrix and the fluorinated moieties. The proposed methodology offers an easy way to get fluorinated carbon/silica hybrid nanomaterials avoiding the harsh reaction conditions usually involved in the preparation of fluorinated materials, and allowing the selective immobilization of specific fluorotails. Moreover, performed oxygen uptake and release kinetics showed that the introduction of fluorinated moieties increases the oxygen exchange, making the material interesting for prospective applications in the biomedical field, as oxygen delivery system, as filler for biocompatible materials, and in the preparation of membranes for the purification of water.

Synthesis and antiproliferative mechanism of action of pyrrolo[3',2':6,7] cyclohepta[1,2-d]pyrimidin-2-amines as singlet oxygen photosensitizers.

A new series of pyrrolo[3,2:6,7]cyclohepta[1,2-d]pyrimidin-2-amines, was conveniently prepared using a versatile and high yielding multistep sequence. A good number of derivatives was obtained and the cellular photocytotoxicity was evaluated inxa0vitro against three different human tumor cell lines with EC50 (0.08-4.96xa0μM) values reaching the nanomolar level. Selected compounds were investigated by laser flash photolysis. The most photocytotoxic derivative, exhibiting a fairly long-lived triplet state (τ ∼ 7xa0μs) and absorbance in the UV-Vis, was tested in the photo-oxidations of 9,10-anthracenedipropionic acid (ADPA) by singlet oxygen. The photosentizing properties are responsible for the compounds ability to photoinduce massive cell death with involvement of mitochondria.

Pyrrolo[3′,2′:6,7]cyclohepta[1,2-b]pyridines with potent photo-antiproliferative activity

Pyrrolo[3,2:6,7]cyclohepta[1,2-b]pyridines were synthesized as a new class of tricyclic system in which the pyridine ring is annelated to a cycloheptapyrrole scaffold, with the aim of obtaining new photosensitizing agents with improved antiproliferative activity and lower undesired toxic effects. A versatile synthetic pathway was approached, which allowed the isolation of derivatives of the title ring system with a good substitution pattern on the pyrrole moiety. Photobiological studies revealed that the majority of the new compounds showed a potent cytotoxic effect upon photoactivation with light of the proper wavelength, especially when decorated with a 2-ethoxycabonyl group and a N-benzyl substituted moiety, with EC50 values reaching the submicromolar level. The mechanism of action was evaluated.