In this contribution we report the design, fabrication and properties of hydrosoluble platinum nanoparticles decorated with a nitric oxide (NO) caging compound. Direct monitoring of NO through an ultrasensitive NO electrode demonstrate that the nanoparticles are stable in the dark but supply NO at nanomolar levels exclusively upon light excitation. The biocompatibility of these nanohybrid systems and their potential in photoactivated anticancer therapy have been explored by in vitro experiments using tumor cell lines. Overall these nanoparticles meet a combination of ideal prerequisites in the context of biomedical applications. Indeed, they associate small sizes, good water solubility and thermal stability under physiological conditions with excellent biocompatibility and appreciable tumor cell mortality upon irradiation with visible light. All these features make our photoactivable nanoparticles very appealing point sources of NO from the viewpoint of practical application in the emerging field of nanomedicine.

The aim of this work was to evaluate the potential anti-inflammatory activity of eleven (5-15) new synthesized derivatives of benzo-thieno[3,2-d]pyrimidine on two cell models, namely human keratinocytes NCTC 2544 and mouse monocyte-macrophages J774. For the synthesis of test compounds an efficient approach was developed: the key isothiocyanate was prepared through a simple and ecological method using di-2-pyridyl thionocarbonate (DPT) in substitution of thiophosgene, a highly toxic agent, and the cyclization reaction of benzo-thiosemicarbazide derivates was performed through Wamhoff methods. This procedure can be a new alternative method economically and environmentally advantageous by the simplicity of procedure, reduction of isolation and purification steps, time, costs, and waste production. The potential anti-inflammatory activity of 5-15 was evaluated by determining the expression of cyclooxygenase (COX)-2, inducible NO synthase (iNOS), and intercellular adhesion molecule-1 (ICAM-1), and the release of prostaglandins (PG)E[Formula: see text] and interleukin-8 (IL-8). Our results demonstrate that the compounds 7, 10, 12, 13, 14, and 15 act as a potent inhibitor of COX-2, iNOS, ICAM-1 expression while also suppressing the production of PGE[Formula: see text] and IL-8 in human keratinocytes NCTC 2544 exposed to interferon-gamma (IFN-[Formula: see text]) and histamine and monocyte-macrophages J774 cells treated with lipopolysaccharides (LPS). In conclusion, some derivatives of benzo-thieno[3,2-d]pyrimidine could be developed as a novel class of anti-inflammatory agents.

In this contribution the design and fabrication of bifunctional, photoresponsive hybrid metal nanoparticle assemblies is reported. Integration of tailored porphyrin and NO photodonor units into ca. 1 nm carboxy-terminated platinum induces the formation of particle nanoassemblies of ca. 10 nm, which are quite soluble in aqueous solution at physiological pH and exhibit a bichromophoric behavior. Direct monitoring of NO through an ultrasensitive NO electrode demonstrates that the nanoparticles are stable in the dark but supply NO at nanomolar level in a way exclusively regulated by light excitation. Besides, the typical red fluorescence arising from the porphyrin centers in the nanoassembly is not quenched extensively, offering a useful tool for mapping the localization of the nanoparticles in bio-environments. Overall these nanohybrids represent appealing bright point sources of NO to be tested in biological research in the perspective of practical application in the emerging field of nanomedicine.

Abstract:The aims of this study were: (i) to explore the structure-activity relationship of some new anti-inflammatory benzothieno[3,2-d]pyrimidin-4-one sulphonamide thio-derivatives 1-11; and (ii) to evaluate the possibility of using the most active compounds as fluorescent probes to determine tumours or their progression. Therefore, to know the precise mechanism by which these compounds interact with cyclooxygenase (COX)-2 enzyme, a molecular docking study was carried out; to assess spectroscopic characteristics, their absorption and emission properties were determined. The results demonstrated that some derivatives of benzothieno[3,2-d] pyrimidine exhibit interesting anti-inflammatory properties related to interactions with active sites of COX-2 and are fluorescent. The antipyrine-bearing compound 4 displayed high COX-2 affinity (ΔG = −9.4) and good fluorescent properties (Φ fl = 0.032). Thus, some members of this new class of anti-inflammatory may be promising for fluorescence imaging of cancer cells that express the COX-2 enzyme. Further in vitro and in vivo studies are needed to confirm this hypothesis.

Eight new sulfonilamidothienopyrimidinone derivatives (1-8) were synthesized and evaluated for their antiinflammatory activity on the human keratinocyte line NCTC 2544. The potential anti-inflammatory activity of the derivatives (1-8) was evaluated by determining, through Western blot, the expression of cyclooxygenase (COX)-2, inducible NO synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), and the release of prostaglandins (PG)E2 and interleukin- 8 (IL-8). Moreover, through ELISA assay, the release of monocyte chemoattractant protein-1 (MCP-1), and interleukin- 8 (IL-8) was analyzed. Our results demonstrated that the derivatives 3, 5, 6 and 8 act as excellent inhibitors of inflammatory markers: iNOS, COX-2, ICAM-1, MCP-1, and IL-8. These findings could be useful for the development of new drugs for the treatment of various inflammatory pathologies.