Copper is an endogenous metal ion that has been studied to prepare a new antitumoral agent with less side-effects. Copper is involved as a cofactor in several enzymes, in ROS production, in the promotion of tumor progression, metastasis, and angiogenesis, and has been found at high levels in serum and tissues of several types of human cancers. Under these circumstances, two strategies are commonly followed in the development of novel anticancer Copper-based drugs: the sequestration of free Copper ions and the synthesis of Copper complexes that trigger cell death. The latter strategy has been followed in the last 40 years and many reviews have covered the anticancer properties of a broad spectrum of Copper complexes, showing that the activity of these compounds is often multi factored. In this work, we would like to focus on the anticancer properties of mixed Cu(II) complexes bearing substituted or unsubstituted 1,10-phenanthroline based ligands and different classes of inorganic and organic auxiliary ligands. For each metal complex, information regarding the tested cell lines and the mechanistic studies will be reported and discussed. The exerted action mechanisms were presented according to the auxiliary ligand/s, the metallic centers, and the increasing complexity of the compound structures.

Five coumarin derivatives, able to coordinate Fe(III) and exhibit a ratiometric and turn-on fluorescence response, were prepared and tested. The derivative with the –OCH₃ substituent exhibited a high fluorescence enhancement in the presence of Fe(III), Ga(III), Au(III) and Y(III). Thanks to the higher stability of the Fe(III) complexes, this molecule could be proposed as a selective fluorescent sensor for the detection of Fe(III) in CH₃CN and CH₃CN : H₂O (1 : 1, v/v) solutions, showing a linear response up to 35.0 μM Fe(III) concentration and a limit of detection of 2.4 μM Fe(III) concentration. The fluorescence response towards this ion was also tested on a solid surface with a simple cellulose paper-strip test. The peculiarity of the proposed sensor lies in its easy and low-cost synthesis, relevant ratiometric response and, since it is derived from a natural product, low impact on the environment and its organisms.

The design of novel antityrosinase agents appears extremely important in medical and industrial sectors because an irregular production of melanin is related to the insurgence of several skin-related disorders (e.g., melanoma) and the browning process of fruits and vegetables. Because melanogenesis also involves a nonenzymatic oxidative process, developing dual antioxidant and antityrosinase agents is advantageous. In this work, we evaluated the antioxidant and tyrosinase inhibition ability of two new bishydroxylated and two new monohydroxylated derivatives of (1E)-2-(1-(2-oxo-2H-chromen-3-yl)ethylidene)hydrazine-1-carbothioamide (T1) using different experimental and computational approaches. The study was also carried out on another monohydroxylated derivative of T1 for comparison. Interestingly, these molecules have more potent tyrosinase-inhibitory properties than the reference compound, kojic acid. Moreover, the antioxidant activity appears to be influenced according to the number and substitution pattern of the hydroxyl groups. The safety of the compounds without (T1), with one (T3), and with two (T6) hydroxyl groups, has also been assessed by studying their cytotoxicity on melanocytes. These results indicate that (1E)-2-(1-(2-oxo-2H-chromen-3-yl)ethylidene)hydrazine-1-carbothioamide and its hydroxylated derivatives are promising molecules for further drug development studies.

The novel copper complex [Cu(phen)2(salubrinal)](ClO4)2 (C0SAL) has been synthesised and characterised. Copper(ii) is coordinated by salubrinal through the thionic group, as shown by the UV-Vis, IR, ESI-MS and tandem mass results, together with the theoretical calculations. The formed complex showed a DPPH radical scavenging ability higher than that of salubrinal alone. Studies on lipid oxidation inhibition showed that the C0SAL concentration, required to inhibit the enzyme, was lower than that of salubrinal. The inhibition of the enzyme could take place via allosteric modulation, as suggested by docking calculations. C0SAL showed a good cytotoxic activity on A2780 cells, 82 fold higher than that of the precursor salubrinal and 1.4 fold higher than that of [Cu(phen)2(H2O)](ClO4)2. Treatment with C0SAL in SKOV3 ovarian cancer cells induced expression of GRP-78 and DDIT3 regulators of ER-stress response. The cytotoxic effect of C0SAL was reverted in the presence of TUDCA, suggesting that C0SAL induces cell death through ER-stress. In A2780 cells treated with C0SAL γ-H2AX was accumulated, suggesting that DNA damage was also involved.

Background: The Enterovirus genus of the Picornaviridae is represented by several viral pathogens that are associated with human disease, namely Poliovirus 1, Enterovirus 71 and Rhinoviruses. Enterovirus 71 has been associated with encephalitis, while Rhinoviruses are a major cause of asthma exacerbations and chronic obstructive pulmonary disease. Based on the structure of both pleconaril and pirodavir, we previously synthesized some original compounds as potential inhibitors of Rhinovirus replication. Methods: These compounds were explored for in vitro antiviral potential on other human pathogenic Enteroviruses, namely Enterovirus 71 on rhabdo-myosarcoma cells, Coxsackievirus B3 on Vero cells, Poliovirus 1 and Echovirus 11 on BGM cells. Results: Activity was confirmed for compound against Rhinovirus 14. Furthermore, few compounds showed a cell-protective effect on Enterovirus 71, presented a marked improvement as compared to the reference drug pleconaril for inhibitory activity on both Enterovirus 71 and Poliovirus 1. The most striking observation was the clear cell protective effect for the set of analogues in a virus-cell-based assay for Echovirus 11 with an effective concentration (EC₅₀) as low as 0.3 µM (Selectivity index or SI = 483), and selectivity indexes greater than 857 (EC₅₀ = 0.6 µM) and 1524 (EC₅₀ = 0.33 µM). Conclusion: Some of the evaluated compounds showed potent and selective antiviral activity against several enterovirus species, such as Enterovirus 71 (EV-A), Echovirus 11 (EV-B), and Poliovirus 1 (EV-C). This could be used as a starting point for the development of other pleconaril/pirodavir-like enterovirus inhibitors with broad-spectrum activity and improved effects as compared to the reference drugs.