Trehalose Lipid Biosurfactant Reduces Adhesion of Microbial Pathogens to Polystyrene and Silicone Surfaces: An Experimental and Computational Approach

Rhodococcus fascians BD8, isolated from Arctic soil, was found to produce biosurfactant when grown on n-hexadecane as the sole carbon source. The glycolipid product was identified as the trehalose lipid with a molecular mass of 848 g mol−1. The purified biosurfactant reduced the surface tension of water from 72 to 34 mN m−1. The critical micelle concentration of trehalose lipid was 0.140 mg mL−1. To examine its potential for biomedical applications, the antimicrobial and antiadhesive activity of the biosurfactant was evaluated against several pathogenic microorganisms. Trehalose lipid showed antimicrobial activity against resistant pathogens. The largest antimicrobial activities of trehalose lipid were observed against Vibrio harveyi and Proteus vulgaris. The highest concentration tested (0.5 mg mL−1) caused a partial (11–34%) inhibition of other Gram-positive and Gram-negative bacteria and 30% inhibition of Candida albicans growth. The trehalose lipid also showed significant antiadhesive properties against all of the tested microorganisms to polystyrene surface and silicone urethral catheters. The biosurfactant showed 95 and 70% antiadhesive activity against C. albicans and Escherichia coli, respectively. Finally, the role and application of trehalose lipid as an antiadhesive compound was investigated by the modification of the polystyrene and silicone surfaces. The intermolecular interaction energy calculations were performed for investigated complexes at the density functional level of theory. The results indicate that the presence of aromatic moieties can be substantial in the stabilization of trehalose lipid-surface complexes. The antimicrobial and antiadhesive activities of trehalose lipid make them promising alternatives to synthetic surfactants in a wide range of medical applications. Based on our findings, we propose that, because of its ability to inhibit microbial colonization of polystyrene and silicone surfaces, trehalose lipid can be used as a surface coating agent

A quantum-chemical study of the binding ability of βXaaHisGlyHis towards copper(II) ion

The present study analyzed binding of Cu2+ to tetrapeptides in water solution at several levels of theoretical approximation. The methods used to study the energetic and structural properties of the complexes in question include semiempirical hamiltonians, density functional theory as well as ab initio approaches including electron correlation effects. In order to shed light on the character of interactions between Cu2+ and peptides, which are expected to be mainly electrostatic in nature, decomposition of interaction energy into physically meaningful components was applied

Long-range corrected DFT calculations of charge-transfer integrals in model metal-free phthalocyanine complexes

An assessment of several widely used exchange--correlation potentials in computing charge-transfer integrals is performed. In particular, we employ the recently proposed Coulomb-attenuated model which was proven by other authors to improve upon conventional functionals in the case of charge-transfer excitations. For further validation, two distinct approaches to compute the property in question are compared for a phthalocyanine dimer

Design and Synthesis of N-Substituted 3,4-Pyrroledicarboximides as Potential Anti-Inflammatory Agents

In the present paper, we describe the biological activity of the newly designed and synthesized series N-substituted 3,4-pyrroledicarboximides 2a–2p. The compounds 2a–2p were obtained in good yields by one-pot, three-component condensation of pyrrolo[3,4-c]pyrrole scaffold (1a–c) with secondary amines and an excess of formaldehyde solution in C2H5OH. The structural properties of the compounds were characterized by 1H NMR, 13C NMR FT-IR, MS, and elemental analysis. Moreover, single crystal X-ray diffraction has been recorded for compound 2h. The colorimetric inhibitor screening assay was used to obtain their potencies to inhibit COX-1 and COX-2 enzymes. According to the results, all of the tested compounds inhibited the activity of COX-1 and COX-2. Theoretical modeling was also applied to describe the binding properties of compounds towards COX-1 and COX-2 cyclooxygenase isoform. The data were supported by QSAR study

Interaction of Oxicam Derivatives with the Artificial Models of Biological Membranes—Calorimetric and Fluorescence Spectroscopic Study

The modified 1,2-benzothiazine analogues designed as new drug candidates and discussed in this paper are oxicam derivatives. Oxicams are a class of non-steroidal anti-inflammatory drugs (NSAIDs). Their biological target is cyclooxygenase (COX), a membrane protein associated with the phospholipid bilayer. In recent decades, it has been proven that the biological effect of NSAIDs may be closely related to their interaction at the level of the biological membrane. These processes are often complicated and the biological membranes themselves are very complex. Therefore, to study these mechanisms, simplified models of biological membranes are used. To characterize the interaction of six oxicam derivatives with DPPC, DMPC and EYPC, artificial models of biological membranes (multi-bilayers or liposomes), differential scanning calorimetry (DSC) and fluorescence spectroscopy techniques were applied. In spectroscopic measurements, two fluorescent probes (Laurdan and Prodan) localized in different membrane segments were used. All tested oxicam derivatives interacted with the lipid bilayers and may penetrate the artificial models of biological membranes. They intercalated into the lipid bilayers and were located in the vicinity of the polar/apolar membrane interface. Moreover, a good drug candidate should not only have high efficiency against a molecular target but also exhibit strictly defined ADMET parameters, therefore these activities of the studied compounds were also estimated

Sustainable Production of Biosurfactant from Agro-Industrial Oil Wastes by <i>Bacillus subtilis</i> and Its Potential Application as Antioxidant and ACE Inhibitor

The microbial conversion of agro-industrial oil wastes into biosurfactants shows promise as a biomass refinery approach. In this study, Bacillus subtilis #309 was applied to produce surfactin using rapeseed and sunflower cakes, the most common oil processing side products in Europe. Studies of the chemical composition of the substrates were performed, to determine the feasibility of oil cakes for surfactin production. Initially, screening of proteolytic and lipolytic activity was performed to establish the capability of B. subtilis #309 for substrate utilization and hence effective surfactin production. B. subtilis #309 showed both proteolytic and lipolytic activity. The process of surfactin production was carefully analyzed by measurement of the surfactin concentration, pH, surface tension (ST) and emulsification index (E24). The maximal surfactin concentration in the sunflower and rapeseed cake medium reached 1.19 ± 0.03 and 1.45 ± 0.09 g/L, respectively. At the same time, a progressive decrease in the surface tension and increase in emulsification activity were observed. The results confirmed the occurrence of various surfactin homologues, while the surfactin C15 was the dominant one. Finally, the analysis of surfactin biological function exhibited antioxidant activity and significant angiotensin-converting enzyme (ACE)-inhibitory activity. The half-maximal inhibitory concentration (IC50) value for ACE inhibition was found to be 0.62 mg/mL for surfactin. Molecular docking of the surfactin molecule to the ACE domains confirmed its inhibitory activity against ACE. Several interactions, such as hydrophobic terms, hydrogen bonds and van der Waals interactions, were involved in the complex stabilization. To the best of our knowledge, this is the first report describing the effect of a lipopeptide biosurfactant, surfactin, produced by B. subtilis for multifunctional properties in vitro, namely the ACE-inhibitory activity and the antioxidant properties, using different assays, such as 2,2-azinobis (3-ethyl-benzothiazoline-6-sulfonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP). Thus, the ACE-inhibitory lipopeptide biosurfactant shows promise to be used as a natural antihypertensive agent

Design and Synthesis of N-Substituted 3,4-Pyrroledicarboximides as Potential Anti-Inflammatory Agents

In the present paper, we describe the biological activity of the newly designed and synthesized series N-substituted 3,4-pyrroledicarboximides 2a–2p. The compounds 2a–2p were obtained in good yields by one-pot, three-component condensation of pyrrolo[3,4-c]pyrrole scaffold (1a–c) with secondary amines and an excess of formaldehyde solution in C2H5OH. The structural properties of the compounds were characterized by 1H NMR, 13C NMR FT-IR, MS, and elemental analysis. Moreover, single crystal X-ray diffraction has been recorded for compound 2h. The colorimetric inhibitor screening assay was used to obtain their potencies to inhibit COX-1 and COX-2 enzymes. According to the results, all of the tested compounds inhibited the activity of COX-1 and COX-2. Theoretical modeling was also applied to describe the binding properties of compounds towards COX-1 and COX-2 cyclooxygenase isoform. The data were supported by QSAR study

Design, Synthesis, Biological Evaluation, and Molecular Docking Study of 4,6-Dimethyl-5-aryl/alkyl-2-[2-hydroxy-3-(4-substituted-1-piperazinyl)propyl]pyrrolo[3,4-<i>c</i>]pyrrole-1,3(2<i>H</i>,5<i>H</i>)-diones as Anti-Inflammatory Agents with Dual Inhibition of COX and LOX

In the present study, we characterize the biological activity of a newly designed and synthesized series of 15 compounds 2-[2-hydroxy-3-(4-substituted-1-piperazinyl)propyl] derivatives of pyrrolo[3,4-c]pyrrole 3a–3o. The compounds were obtained with good yields of pyrrolo[3,4-c]pyrrole scaffold 2a–2c with secondary amines in C2H5OH. The chemical structures of the compounds were characterized by 1H-NMR, 13C-NMR, FT-IR, and MS. All the new compounds were investigated for their potencies to inhibit the activity of three enzymes, i.e., COX-1, COX-2, and LOX, by a colorimetric inhibitor screening assay. In order to analyze the structural basis of interactions between the ligands and cyclooxygenase/lipooxygenase, experimental data were supported by the results of molecular docking simulations. The data indicate that all of the tested compounds influence the activity of COX-1, COX-2, and LOX