Purpose. Staphylococcus aureus infections have contributed to the global healthcare burden, particularly with regard to hospital-acquired meticillin-resistant S. aureus (MRSA) infections. Methodology. This study describes the antibacterial activity of diacetylcurcumin (DAC) against meticillin-susceptible S. aureus/MRSA biofilm formation, survival, metabolic activity and structure; its ability to prevent bacterial adhesion to human cells; and toxicity in Galleria mellonella larvae. Results. DAC showed excellent antibacterial activity, with MIC ranging between 17.3 and 34.6 µmol l−1, and minimum bactericidal concentration ranging between 69 and 277 µmol l−1. It significantly reduced bacterial biofilm survival – by 22–63 % (at MIC, 10×MIC or 100×MIC) as compared to the 25–42 % reduction by vancomycin (P<0.0001) – and severely affected biofilm cell structures, leading to damaged architecture and the formation of amorphous cell clusters. Treatment with DAC (MIC/4) decreased bacterial adhesion to HaCaT keratinocytes from 1 to 5 h (P<0.0001). Finally, DAC demonstrated low toxicity in G. mellonella at its effective anti-biofilm concentrations. Conclusion. These findings open new avenues for the study of this curcumin derivative as an excellent prototype with anti-MRSA activity.

Alkyl gallates are compounds with reported antibacterial activity. One of the modes of action is binding of the alkyl gallates to the bacterial membrane and interference with membrane integrity. However, alkyl gallates also cause cell elongation and disruption of cell division in the important plant pathogen Xanthomonas citri subsp. citri, suggesting that cell division proteins may be targeted by alkyl gallates. Here, we use Bacillus subtilis and purified B. subtilis FtsZ to demonstrate that FtsZ is a direct target of alkyl gallates. Alkyl gallates disrupt the FtsZ-ring in vivo, and cause cell elongation. In vitro, alkyl gallates bind with high affinity to FtsZ, causing it to cluster and lose its capacity to polymerize. The activities of a homologous series of alkyl gallates with alkyl side chain lengths ranging from five to eight carbons (C5-C8) were compared and heptyl gallate was found to be the most potent FtsZ inhibitor. Next to the direct effect on FtsZ, alkyl gallates also target B. subtilis membrane integrity – however the observed anti-FtsZ activity is not a secondary effect of the disruption of membrane integrity. We propose that both modes of action, membrane disruption and anti-FtsZ activity, contribute to the antibacterial activity of the alkyl gallates. We propose that heptyl gallate is a promising hit for the further development of antibacterials that specifically target FtsZ.

Hepatitis C virus (HCV) is one of the leading causes of liver diseases and transplantation worldwide. The current available therapy for HCV infection is based on interferon-α, ribavirin and the new direct-acting antivirals (DAAs), such as NS3 protease and NS5B polymerase inhibitors. However, the high costs of drug design, severe side effects and HCV resistance presented by the existing treatments demonstrate the need for developing more efficient anti-HCV agents. This study aimed to evaluate the antiviral effects of sorbifolin (1) and pedalitin (2), two flavonoids fromPterogyne nitenson the HCV replication cycle. These compounds were investigated for their anti-HCV activities using genotype 2a JFH-1 subgenomic replicons and infectious virus systems. Flavonoids1and2inhibited virus entry up to 45.0% and 78.7% respectively at non-cytotoxic concentrations. The mechanism of the flavonoid2block to virus entry was demonstrated to be by both the direct action on virus particles and the interference on the host cells. Alternatively, the flavonoid1activity was restricted to its virucidal effect. Additionally, no inhibitory effects on HCV replication and release were observed by treating cells with these flavonoids. These data are the first description of1and2possessingin vitroanti-HCV activity.

Curcumin is the main constituent of turmeric, a seasoning popularized around the world with Indian cuisine. Among the benefits attributed to curcumin are anti‐inflammatory, antimicrobial, antitumoral, and chemopreventive effects. Besides, curcumin inhibits the growth of the gram‐positive bacterium Bacillus subtilis . The anti‐ B. subtilis action happens by interference with the division protein FtsZ, an ancestral tubulin widespread in Bacteria . FtsZ forms protofilaments in a GTP‐dependent manner, with the concomitant recruitment of essential factors to operate cell division. By stimulating the GTPase activity of FtsZ, curcumin destabilizes its function. Recently, curcumin was shown to promote membrane permeabilization in B. subtilis . Here, we used molecular simplification to dissect the functionalities of curcumin. A simplified form , in which a monocarbonyl group substituted the β‐diketone moiety, showed antibacterial action against gram‐positive and gram‐negative bacteria of clinical interest. The simplified curcumin also disrupted the divisional septum of B. subtilis ; however, subsequent biochemical analysis did not support a direct action on FtsZ. Our results suggest that the simplified curcumin exerted its function mainly through membrane permeabilization, with disruption of the membrane potential necessary for FtsZ intra‐cellular localization. Finally, we show here experimental evidence for the requirement of the β‐diketone group of curcumin for its interaction with FtsZ.

Aim: Gallic acid and its ester derivatives have shown antifungal activity in vitro. This study was performed to investigate their activity against Candida albicans and their toxicity in the animal models Caenorhabditis elegans and zebrafish embryos. Results: The compounds protected worms from C. albicans infection. The dodecyl gallate was the most effective. In zebrafish embryo, gallic acid and dodecyl gallate were the least toxic. Conclusion: Gallic acid and its ester derivatives have potential for in vivo use against C. albicans infection. The antifungal effects and toxicity of gallate esters in these alternative animal models were dependent on carbon chain length.