A new strain, namely Lysinibacillus sp. BV152.1 was isolated from the rhizosphere of ground ivy (Glechoma hederacea L.) producing metabolites with potent ability to inhibit biofilm formation of an important human pathogens Pseudomonas aeruginosa PAO1, Staphylococcus aureus, and Serratia marcescens. Structural characterization revealed di-rhamnolipids mixture containing rhamnose (Rha)-Rha-C10-C10, Rha-Rha-C8-C10 and Rha-Rha-C10-C12 in the ratio 7:2:1 as the active principle. Purified di-rhamnolipids as well as commercially available di-rhamnolipids (Rha-Rha-C10-C10, 93%) were used as the substrate for the chemical derivatization for the first time, yielding three semi-synthetic amide derivatives, benzyl-, piperidine- and morpholine. A comparative study of the anti-biofilm, antibacterial and cytotoxic properties revealed that di-Rha from Lysinibacillus sp. BV152.1 were more potent in biofilm inhibition, both cell adhesion and biofilm maturation, than commercial di-rhamnolipids inhibiting 50% of P. aeruginosa PAO1 biofilm formation at 50 μg mL-1 and 75 μg mL-1, respectively. None of the di-rhamnolipids exhibited antimicrobial properties at concentrations of up to 500 μg mL-1. Amide derivatization improved inhibition of biofilm formation and dispersion activities of di-rhamnolipids from both sources, with morpholine derivative being the most active causing more than 80% biofilm inhibition at concentrations 100 μg mL-1. Semi-synthetic amide derivatives showed increased antibacterial activity against S. aureus, and also showed higher cytotoxicity. Therefore, described di-rhamnolipids are potent anti-biofilm agents and the described approach can be seen as viable approach in reaching new rhamnolipid based derivatives with tailored biological properties.

Disruption of the redox balance in the body causes oxidative stress that can initiate many diseases. While antioxidants reduce the level of oxidizing compounds in the medium, prooxidants promote the opposite process and have been used in therapies in particular those of cancer diseases. In this study, a series of azolyl lactones, were tested in human serum as a biological matrix and the obtained values of their oxy scores (OS) were compared. The antioxidative properties of these compounds were also tested under conditions of induced oxidative stress using an external prooxidant, t-butylhydroperoxide. The results showed that the sulphur analogue 4-azolyl coumarin 5 has the best antioxidant properties (OS ?2.2), while the halogenated derivatives of pyrazolylcoumarin 7 and 8 act as prooxidants, but successfully resist oxidative stress (OS 2.7 and 2.0, respectively). Related phthalides and isocoumarins showed prooxidative properties, but azolyl isocoumarins 10 and 11 show the strongest resistance to oxidative stress, reflected in their negative oxy score value (OS ?2.1 and ?1.1, respectively). The results demonstrated that combining two pharmacophores with known redox properties can produce potent compounds in both directions, with the antioxidative and the prooxidative characteristics.

The redox balance plays a crucial role in maintaining biological processes under normal conditions. Antioxidants inhibit and reduce harmful oxidation processes, while pro-oxidants can act as anti-cancer agents by promoting ROS-mediated cell death. The aim of this study is to compare the redox properties of seven newly synthesised tribromopyrrole derivatives with three novel and four previously synthesized non-halogenated analogues in an in vitro model (in human serum) and with exogenously induced oxidative stress. The obtained values of their oxy scores (OS) were compared and the result showed that four non-halogenated pyrrole derivatives with secondary amide group M2, M10, M11 and M12 have lower OS values than Trolox, a water-soluble analogue of vitamin E with proven antioxidant properties. All four compounds show strong resistance to oxidative stress, which is reflected in the maintenance of negative OS values when exposed to exogenous oxidative stress using TBH in the reaction mixture. This capability to resist invading ROS should be expected also in an endogenous environment, where constant prooxidant production takes place at a low, homeostatic level, but even more so in pathological conditions. The tribrominated derivative M15 showed prooxidant activity with a significantly higher OS value than all other compounds tested. The comparison of the dose-response of Trolox and the five compounds with the lowest OS also shows that compounds M2, M7 and M10 have better antioxidant activity than Trolox.