Novel C3-Methylene-Bridged Indole Derivatives with and without Substituents at N1: The Influence of Substituents on Their Hemolytic, Cytoprotective, and Antimicrobial Activity.

Alkaloids are natural compounds useful as scaffolds for discovering new bioactive molecules. This study utilized alkaloid gramine to synthesize two groups of C3-substituted indole derivatives, which were either functionalized at N1 or not. The compounds were characterized by spectroscopic methods. The protective effects of the new compounds against in vitro oxidative hemolysis induced by standard oxidant 2,2'-azobis(2-amidinopropane dihydro chloride (AAPH) on human erythrocytes as a cell model were investigated. Additionally, the compounds were screened for antimicrobial activity. The results indicated that most of the indole derivatives devoid of the N1 substitution exhibited strong cytoprotective properties. The docking studies supported the affinities of selected indole-based ligands as potential antioxidants. Furthermore, the derivatives obtained exhibited potent fungicidal properties. The structures of the eight derivatives possessing indole moiety bridged to the imidazole-, benzimidazole-, thiazole-, benzothiazole-, and 5-methylbenzothiazoline-2-thiones were determined by X-ray diffraction. The C=S bond lengths in the thioamide fragment pointed to the involvement of zwitterionic structures of varying contribution. The predominance of zwitterionic mesomers may explain the lack of cytoprotective properties, while steric effects, which limit multiple the hydrogen-bond acceptor properties of a thione sulfur, seem to be responsible for the high hemolytic activity.

Temporal arsenic form changes dynamics and accumulation patterns in Tilia cordata Mill. seedlings: Insights into metalloid transformation and tolerance mechanisms in trees.

Arsenic (As) remediation is challenging due to the complex nature and the persistence of these metalloid compounds. While it may seem that differences between As forms influence have been extensively described, new findings challenge the previously accepted knowledge, particularly for woody plants. Therefore, this study focused on 2-year-old Tilia cordata Mill. seedlings early (0, 2, 4, 12, 24 h) and late (3, 7, 12, 18, 25, 33 days) responses during growth under: As(III), As(V) or dimethylarsinic acid (DMA) (0.3 mM). Time-dependent transformations of As forms, distribution in plants, and microbiological characteristics (actinobacteria, bacteria, fungi, enzyme activity) were investigated. The highest increase in total As content was observed in plants exposed to As(V) and As(III). Dynamic metalloid form changes in the solution and tree organs were indicated. The most phytotoxic was DMA. This form was the main factor limiting the growth and effective accumulation of As. Despite experimenting in hydroponics, microorganisms played an important role in As form transformations, suggesting the potential for microbial-assisted dendroremediation strategies. The study confirmed that trees can convert more toxic forms into less toxic ones (e.g. As(III) to phytochelatins - As(III)-(PC3)), whose presence in roots seedlings exposed to As(III) and As(V) has been identified. The formation of hydrophobic forms (e.g. dimethylarsinoyl lipid) in the roots of seedlings grown under As(V) was confirmed. It is the first discovery for trees, previously observed only in bacteria and algae. The dynamics of metalloid form changes indicated that T. cordata transforms As forms according to their needs, which may give tree species an advantage in phytoremediation techniques. It holds great promise for the potential of dendroremediation.

Synthesis, Structure and Biological Activity of Indole-Imidazole Complexes with ZnCl2: Can Coordination Enhance the Functionality of Bioactive Ligands?

The ability of the indole-imidazole hybrid ligands to coordinate with the Zn(II) ion and the resulting structures of this new class of coordination compounds were analyzed in order to determine their structural properties and biological functionalities. For this purpose, six novel Zn(II) complexes, [Zn(InIm)2Cl2] (1), [Zn(InMeIm)2Cl2] (2), [Zn(IniPrIm)2Cl2] (3), [Zn(InEtMeIm)2Cl2] (4), [Zn(InPhIm)2Cl2] (5) and [Zn2(InBzIm)2Cl2] (6) (where InIm is 3-((1H-imidazol-1-yl)methyl)-1H-indole), were synthesized by the reactions of ZnCl2 and the corresponding ligand in a 1:2 molar ratio in methanol solvent at an ambient temperature. The structural and spectral characterization of these complexes was performed using NMR, FT-IR and ESI-MS spectrometry and elemental analysis, and the crystal structures of 1-5 were determined using single-crystal X-ray diffraction. Complexes 1-5 form polar supramolecular aggregates by utilizing, for this purpose, the N-H(indole)∙∙∙Cl(chloride) intermolecular hydrogen bonds. The assemblies thus formed differ depending on the distinctive molecular shape, which can be either compact or extended. All complexes were screened for their hemolytic, cytoprotective, antifungal, and antibacterial activities. The results show that the cytoprotective activity of the indole/imidazole ligand significantly increases upon its complexation with ZnCl2 up to a value comparable with the standard antioxidant Trolox, while the response of its substituted analogues is diverse and less pronounced.

Indole Derivatives Bearing Imidazole, Benzothiazole-2-Thione or Benzoxazole-2-Thione Moieties-Synthesis, Structure and Evaluation of Their Cytoprotective, Antioxidant, Antibacterial and Fungicidal Activities.

In the search for new bioactive compounds, a methodology based on combining two molecules with biological properties into a new hybrid molecule was used to design and synthesize of a series of ten indole derivatives bearing imidazole, benzothiazole-2-thione, or benzoxazole-2-thione moieties at the C-3 position. The compounds were spectroscopically characterized and tested for their antioxidant, antibacterial, and fungicidal activities. The crystal structures were determined for five of them. Comparison of the closely related structures containing either benzothiazole-2-thione or benzoxazole-2-thione clearly shows that the replacement of -S- and -O- ring atoms modify molecular conformation in the crystal, changes intermolecular interactions, and has a severe impact on biological activity. The results indicate that indole-imidazole derivatives with alkyl substituent exhibit an excellent cytoprotective effect against AAPH-induced oxidative hemolysis and act as effective ferrous ion chelating agents. The indole-imidazole compound with chlorine atoms inhibited the growth of fungal strains: Coriolus versicolor (Cv), Poria placenta (Pp), Coniophora puteana (Cp), and Gloeophyllum trabeum (Gt). The indole-imidazole derivatives showed the highest antibacterial activity, for which the largest growth-inhibition zones were noted in M. luteus and P. fluorescens cultures. The obtained results may be helpful in the development of selective indole derivatives as effective antioxidants and/or antimicrobial agents.

Protozoa and metazoa relations to technological conditions of non-woven textile filters for wastewater treatment.

The objective of this study was a preliminary identification of basic groups of micro-organisms in the cross-sectional profile of geotextile filters for septic tank effluent (STE) treatment and their relations to technological conditions. Reactors with textile filters treating wastewater were investigated on a semi-technical scale. Filters were vertically situated and STE was filtered through them under hydrostatic pressure at a wastewater surface height of 7-20 cm. Filters were made of four layers of non-woven TS 20 geotextile of 0.9 mm thickness. Various groups of organisms were observed; the most abundant group comprised free-swimming and crawling ciliates, less abundant were stalked ciliates and the least numerous were nematodes. The individual counts of all groups of micro-organisms investigated during the study were variable according to time and space. The high abundance of Opercularia, a commonly observed genus of stalked ciliates, was related to the high efficiency of wastewater treatment and dissolved oxygen concentration of about 1.0 g/m3. Numbers of free-swimming and crawling ciliates had a tendency to decrease in relation to the depth of filter cross-sectional profile. The variability in counts of particular groups of organisms could be related to the local stress conditions. No correlation between identified organism count and total mass concentration in the cross-sectional filter profile was found.

Bacteria in non-woven textile filters for domestic wastewater treatment.

The objective of this study was preliminary identification of heterotrophic and ammonia oxidizing bacteria (AOB) cell concentration in the cross-sectional profile of geotextile filters for wastewater treatment. Filters of thicknesses 3.6 and 7.2 mm, made of non-woven textile TS20, were supplied with septic tank effluent and intermittently dosed and filtered under hydrostatic pressure. The cumulative loads of chemical oxygen demand (COD) and total solids were about 1.36 and 1.06 kg/cm2, respectively. The filters under analysis reached a relatively high removal efficiency for organic pollution 70-90% for biochemical oxygen demand (BOD5) and 60-85% for COD. The ammonia nitrogen removal efficiency level proved to be unstable (15-55%). Biomass samples for dry mass identification were taken from two regions: continuously flooded with wastewater and intermittently flooded with wastewater. The culturable heterotrophic bacteria were determined as colony-forming units (CFUs) on microbiological-selective media by means of the plate method. AOB and nitrite oxidizing bacteria (NOB) were examined using the FISH technique. A relatively wide range of heterotrophic bacteria was observed from 7.4×10(5)/cm2 to 3.8×10(6)/cm2 in geotextile layers. The highest concentration of heterotrophic bacteria (3.8×10(6)/cm2) was observed in the first layer of the textile filter. AOB were identified occasionally--about 8-15% of all bacteria colonizing the last filter layer, but occasionally much higher concentrations and ammonia nitrogen efficiency were achieved. Bacteria oxidizing nitrite to nitrate were not observed. The relation of total and organic fraction of biomass to culturable heterotrophic bacteria was also found.