Background: Malignant melanoma is one of the most aggressive skin cancer and chemotherapeutic agents currently in use are still unsatisfactory. Prevention and early diagnosis are the only effective tools against this tumour whose incidence and mortality rates are highly increased during the last decades in fair skin populations. Therefore the search for novel therapeutic approaches is warranted. Aim of this work was to identify and test new compounds with antiproliferative and cytotoxic activity on melanoma cells. We tested eugenol together with six natural and synthetic eugenol-related compounds for their capability to inhibit cell growth on primary melanoma cell lines established from patients' tissue samples. Results: Eugenol and isoeugenol monomers and their respective O-methylated forms did not show to inhibit melanoma cells proliferation. Conversely, the dimeric forms (biphenyls) showed some antiproliferative activity which was mild for dehydrodieugenol, higher for its O,O'- methylated form (O,O'-dimethyl-dehydrodieugenol), and markedly pronounced for the racemic mixture of the brominated biphenyl (6,6'-dibromo-dehydrodieugenol) (S7), being its enantiomeric form (S) the most effective compared to the other compounds. Such activity resulted to be selective against tumour cells, without affecting cultured normal human skin fibroblasts. Dose and time dependence curves have been obtained for the enantiomeric form S7-(S). Then IC₅₀ and minimal effective doses and times have been established for the melanoma cell lines tested. TUNEL and phosphatidylserine exposure assays demonstrated the occurrence of apoptotic events associated with the antiproliferative activity of S7-(S). Cytotoxic activity and apoptosis induced by treating melanoma cells with eugenol-related biphenyls was partially dependent by caspase activation. Conclusion: Our findings demonstrate that the eugenol related biphenyl (S)-6,6'-dibromo-dehydrodieugenol elicits specific antiproliferative activity on neuroectodermal tumour cells partially triggering apoptosis and its activity should be further investigated on in vivo melanoma models in order to evaluate the real anticancer effectiveness on such tumour.

The antifungal activity of magnolol and honokiol, two naturally occurring hydroxylated biphenyls, and of their synthetic derivatives was evaluated on a collection of representative isolates of Fusarium oxysporum, F. solani and F. verticillioides of clinical and ecological concern. The tested compounds were proposed as a ‘natural’ alternative to conventional fungicides, even though a larger range of concentrations (5–400 μg/ml) was applied. The activity of magnolol and honokiol was compared with that of terbinafine (0.1–10 μg/ml), and fluconazole (1–50 μg/ml), two fungicides widely used in treating fungal infections on humans. Magnolol showed similar fungicidal activity compared to fluconazole, whereas honokiol was more effective in inhibiting mycelium growth compared to this fungicide on all tested clinical Fusarium spp. isolates. Compared to terbinafine, honokiol showed similar antifungal activity when tested on clinical F. solani isolates, whereas magnolol was less effective at all selected concentrations (5–400 μg/ml). The different position of the phenol-OH group, as well as its protection, explain different in vitro activities between magnolol, honokiol, and their derivatives. Furthermore, magnolol showed mycelium dry weight reduction at a concentration of 0.5 mM when tested on a set of agricultural isolates of Fusaria, leading to complete inhibition of some of them. Magnolol and honokiol are proposed as efficient and safe candidates for treating clinically relevant Fusaria.

This study compares the ability to scavenge different peroxyl radicals and to act as chain-breaking antioxidants of monomers related to curcumin (1): dehydrozingerone (2), zingerone (3), (2Z,5E)-ethyl 2-hydroxy-6-(4-hydroxy-3-methoxyphenyl)-4-oxohexa-2,5-dienoate (4), ferulic acid (5) and their corresponding C₂-symmetric dimers 6–9. Four models were applied: model 1 – chemiluminescence (CL) of a hydrocarbon substrate used for determination of the rate constants (k_A) of the reactions of the antioxidants with peroxyl radicals; model 2 – lipid autoxidation (lipidAO) used for assessing the chain-breaking antioxidant efficiency and reactivity; model 3 – oxygen radical absorbance capacity (ORAC), which yields the activity against peroxyl radicals generated by an azoinitiator; model 4 – density functional theory (DFT) calculations at UB3LYP/6-31+G(d,p) level, applied to explain the structure–activity relationship. Dimers showed 2–2.5-fold higher values of k_A than their monomers. Model 2 gives information about the effects of the side chains and revealed much higher antioxidant activity for monomers and dimers with α,β-unsaturated side chains. Curcumin and 6 in fact are dimers of the same monomer 2. We conclude that the type of linkage between the two “halves” by which the molecule is made up does not exert influence on the antioxidant efficiency and reactivity of these two dimers. The dimers and the monomers demonstrated higher activity than Trolox (10) in aqueous medium (model 3). A comparison of the studied compounds with DL-α-tocopherol (11), Trolox and curcumin is made. All dimers are characterized through lower bond dissociation enthalpies (BDEs) than their monomers (model 4), which qualitatively supports the experimental results.

Fusarium spp. are ubiquitous fungi able to cause Fusarium head blight and Fusarium foot and root rot on wheat. Among relevant pathogenic species, Fusarium graminearum and Fusarium culmorum cause significant yield and quality loss and result in contamination of the grain with mycotoxins, mainly type B trichothecenes, which are a major health concern for humans and animals. Phenolic compounds of natural origin are being increasingly explored as fungicides on those pathogens. This review summarizes recent research activities related to the antifungal and anti-mycotoxigenic activity of natural phenolic compounds against Fusarium, including studies into the mechanisms of action of major exogenous phenolic inhibitors, their structure-activity interaction, and the combined effect of these compounds with other natural products or with conventional fungicides in mycotoxin modulation. The role of high-throughput analysis tools to decipher key signaling molecules able to modulate the production of mycotoxins and the development of sustainable formulations enhancing potential inhibitors’ efficacy are also discussed.

The hepatocellular carcinoma is one of the most common malignant tumour with high level of mortality rate due to its rapid progression and high resistance to conventional chemotherapies. Thus, the search for novel therapeutic leads is of global interest. Herein, a small set of derivatives of magnolol 1 and honokiol 2, the main components of Magnolia grandiflora and Magnolia obovata, were evaluated in in vitro assay using tumoral hepatocytes. The pro-drug approach was applied as versatile strategy to the improve bioactivity of the compounds by careful transformation of the hydroxyl groups of magnolol 1 and honokiol 2 in suitable ester derivatives. Compounds 10 and 11 resulted to be more potent than the parental honokiol 2 at concentration down to 1 μM with complete viability of treated fibroblast cells up to concentrations of 80 μM. The combination of a butyrate ester and a bare phenol-OH group in the honokiol structure seemed to play a significant role in the antiproliferative activity identifying an interesting pharmacological clue against hepatocellular carcinoma.