Efficiency of phytoremediation and identification of biotransformation pathways of fluoroquinolones in the aquatic environment.

Phytoremediation is a low-cost and sustainable green technology that uses plants to remove organic and inorganic pollutants from aquatic environments. The aim of this study was to investigate the phytoextraction, phytoaccumulation, and phytotransformation of three fluoroquinolones (FQs) (ciprofloxacin [CIP], enrofloxacin [ENF], and levofloxacin [LVF]) by Japanese radish (Raphanus sativus var. longipinnatus) and duckweed (Lemma minor). Determination of FQs and identification of their transformation products (TPs) were performed using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Inter-tissue translocation of FQs in Japanese radish tissues depended on their initial concentration in the medium. CIP (IT = 14.4) and ENF (IT = 17.0) accumulated mainly in radish roots, while LVF in leaves (IT = 230.8) at an initial concentration of 10 µg g-1. CIP (2,104 ng g-1) was detected in the highest concentration, followed by ENF (426.3 ng g-1) and LVF (273.3 ng g-1) in the tissues of both plants. FQs' bioaccumulation factors were significantly higher for duckweed (1.490-18.240) than Japanese radish (0.027-0.103). The removal of FQs from water using duckweed was mainly due to their photolysis and hydrolysis than plant sorption. In the screening, analysis detected 29 FQ TPs. The biotransformation pathways of FQs are described in detail, and the factors that influence their formation are indicated.

This study has presented the efficiency of fluoroquinolone (FQ) residues phytoextraction from water by two plant species (water duckweed, Japanese radish). The use of two plant species allowed for a holistic study of the FQ phytoremediation process by determining the efficiency of extraction, tissue distribution, bioaccumulation tendency, and biotransformation. The research gap regarding FQ transformation products in the phytoremediation process and the factors determining their formation has been filled. This study indicated that duckweed can be used with great efficiency to purify water from FQ contamination.

Glycoconjugates of Mucochloric Acid-Synthesis and Biological Activity.

The pharmacological effects of the presence of a sugar moiety, 1,2,3-triazole ring and silyl groups in the structure of biologically active compounds have been extensively studied in drug design and medicinal chemistry. These components can be useful tools to tailoring the bioavailability of target molecules. Herein we present the study on the impact of the sugar substituent structure and triisopropylsilyl group presence on the anticancer activity of mucochloric acid (MCA) derivatives containing the furan-2(5H)-one or 2H-pyrrol-2-one core. The obtained results clearly indicated that tested compounds caused a significant decrease in cell viability of HCT116 and MCF-7 cell lines. MCF-7 cells indicate serious resistance toward investigated compounds in comparison with HCT116 cell line, it suggests that estrogen-dependent breast cancer cells are significantly less sensitive to the tested derivatives. Depending on the structure of the sugar, the type and site of connection with the furanone or 2H-pyrrol-2-one derivative and the presence of the silyl group, the selectivity of the compound towards cancer cells can be controlled. The obtained results may have an impact on the design of new furanone-based anticancer compounds.

Transient binding sites at the surface of haloalkane dehalogenase LinB as locations for fine-tuning enzymatic activity.

The haloalkane dehalogenase LinB is a well-known enzyme that contains buried active site and is used for many modelling studies. Using classical molecular dynamics simulations of enzymes and substrates, we searched for transient binding sites on the surface of the LinB protein by calculating maps of enzyme-ligand interactions that were then transformed into sparse matrices. All residues considered as functionally important for enzyme performance (e.g., tunnel entrances) were excluded from the analysis to concentrate rather on non-obvious surface residues. From a set of 130 surface residues, twenty-six were proposed as a promising improvement of enzyme performance. Eventually, based on rational selection and filtering out the potentially unstable mutants, a small library of ten mutants was proposed to validate the possibility of fine-tuning the LinB protein. Nearly half of the predicted mutant structures showed improved activity towards the selected substrates, which demonstrates that the proposed approach could be applied to identify non-obvious yet beneficial mutations for enzyme performance especially when obvious locations have already been explored.

Effect of Selected Silyl Groups on the Anticancer Activity of 3,4-Dibromo-5-Hydroxy-Furan-2(5H)-One Derivatives.

The pharmacological effects of carbon to silicon bioisosteric replacements have been widely explored in drug design and medicinal chemistry. Here, we present a systematic investigation of the impact of different silyl groups on the anticancer activity of mucobromic acid (MBA) bearing furan-2(5H)-one core. We describe a comprehensive characterization of obtained compounds with respect to their anticancer potency and selectivity towards cancer cells. All four novel compounds exert stronger antiproliferative activity than MBA. Moreover, 3b induce apoptosis in colon cancer cell lines. A detailed investigation of the mechanism of action revealed that 3b activity stems from the down-regulation of survivin and the activation of caspase-3. Furthermore, compound 3b attenuates the clonogenic potential of HCT-116 cells. Interestingly, we also found that depending on the type of the silyl group, compound selectivity towards cancer cells could be precisely controlled. Collectively, we demonstrated the utility of silyl groups for adjusting both the potency and selectivity of silicon-containing compounds. These data reveal a link between the types of silyl group and compound potency, which could have bearings for the design of novel silicon-based anticancer drugs.

Anticancer Activity and Topoisomerase II Inhibition of Naphthalimides with ω-Hydroxylalkylamine Side-Chains of Different Lengths.

BACKGROUND: The substituted 1,8-Naphthalimides (1H-benzo[de]isoquinoline-1,3(2H)- diones) are known as DNA intercalators stabilizing DNA-Topoisomerase II complexes. This interaction disrupts the cleavage-relegation equilibrium of Topo II, resulting in formation of broken strands of DNA. OBJECTIVE: To investigate the influence of type of substituents and substitution positions in 1,8- naphthalimde skeleton on the inhibition of Topoisomerase II activity. METHODS: The starting 1,8-naphthalimide were prepared from acenaphthene by introduction of appropriate substituents followed by condensation with ω-hydroxylakylamines of different chain length. The substituents were introduced to 1,8-naphthalimide molecule by nucleophilic substitution of leaving groups like nitro or bromo present in 4 or 4,5- positions using the ω- hydroxylalkylamines. The bioactivity of obtained compounds was examined in model cell lines. RESULTS: Antiproliferative activity of selected compounds against HCT 116 human colon cancer cells, human non-small cell lung cells A549 and non-tumorigenic BEAS-2B human bronchial epithelium cells was examined. Several of investigated compounds exhibit a significant activity (IC50 µM to 7 µM) against model cancer cell lines. It was demonstrated that upon treatment with concentration of 200 µM, all derivatives display Topo II inhibitory activity, which may be compared with activity of Amonafide. CONCLUSION: The replacement of the nitro groups in the chromophore slightly reduces its anticancer activities, whereas the presence of both nitro group and ω-hydroxylalkylamine chain resulted in seriously increased anticancer activity. Obtained compounds showed Topo II inhibitory activity, moreover, influence of the substitution pattern on the ability to inhibit Topo II activity and cancer cells proliferation was observed.

Simple 2(5H)-furanone derivatives with selective cytotoxicity towards non-small cell lung cancer cell line A549 - Synthesis, structure-activity relationship and biological evaluation.

A series of 5-alkoxy derivatives of 3,4-dichloro-5-hydroxyfuran-2-(5H)-one (mucochloric acid, MCA) were obtained and subsequently subjected to modification in the C-4 position of 2(5H)-furanone ring. The cytotoxicity of newly synthesized compounds was evaluated in MTT assay against non-small cell lung cancer (A549) and healthy lung epithelial cell line (BEAS-2B). The derivatives containing a branched alkoxy substituent in the C-5 position demonstrated the highest anticancer properties, whereas modification of compounds in the C-4 position of 2(5H)-furanone ring only slightly improve their antiproliferative properties. Compounds 12 and 15 exhibited the best selectivity towards A549 cells and were also evaluated in a panel of cancer cell lines of different origin. Further investigation revealed that treatment of A549 cell line with compounds 12 and 15 led to G2 phase cell cycle arrest and induction of caspase-independent cell death. Moreover, compound 12 was found to act synergistically with erlotinib.

Synthesis and preliminary biological assay of uridine glycoconjugate derivatives containing amide and/or 1,2,3-triazole linkers.

A series of UDP-sugar analogues was synthesized and their preliminary biological activity was evaluated. Glycoconjugates of uridine 1 and 2 were synthesized by condensation of uridine-5'-carboxylic acid and 1-amino sugars derivatives of d-glucose and d-galactose, glycoconjugates 3 and 4 were synthesized by azide-alkyne 1,3-dipolar cycloaddition (CuAAC) of 1-azido sugars and propargylamide derivatives of uridine while glycoconjugates 5 and 6 were synthesized by CuAAC of propargyl ß-O-glycosides and 5'-azido uridine. Evaluation of inhibitory activity of compounds 1-6 against commercially available ß-1,4-galactosyltransferase I (ß4GalT) show that compound 5 inhibited the enzyme in µmolar range. Additionally, the antitumor activity of the obtained glycoconjugates 1-6 were tested using MTT assay.