Inhibition of tumour and non-tumour cell proliferation by pygidial gland secretions of four ground beetle species (Coleoptera: Carabidae)

Inhibition of the proliferation of human tumour cells and porcine non-tumour cells by the pygidial gland secretion released by adults of four ground beetle species was observed in this study.The sulphorhodamine B(SRB)assay was applied to establish the percentages of inhibition of the net growth of four human tumour cell lines and porcine liver primary non-tumour cells. The secretions of all tested ground beetle species were shown to have an antiproliferative effect on the tested cell lines. Special emphasisis put on the secretion of Abax parallelepipedus,which showed the highest anti tumour potential and weakest inhibition of non-tumour cell proliferation.The anti tumour and antiproliferative potential of the pygidial gland secretions of ground beetles is here demonstrated for the first time.It is suggested that certain organic acids are responsible for the action.Further investigation needs to be conducted in order to better understand the mechanisms governing the observed cytotoxic and antitumour activity.The study was financially supported by the Serbian Ministry of Education, Science, and Technological Development (Grants Nos. 173038 and 173032) and the Foundation for Science and Technology (FCT, Portugal) (Grant No. SFRH/BPD/68344/2010).info:eu-repo/semantics/publishedVersio

In silico estimation of COX-2 and 5-LOX inhibitory potential of some novel thiourea derivatives of naproxen

Design of dual COX-2/5-LOX inhibitors can be considered an adequate approach in the development of new anti-inflammatory drugs with less pronounced side effects. The aim of the present research was to examine the binding potential of the seven newly designed thiourea derivatives of naproxen towards COX-2 and 5-LOX. The binding analysis of ligand conformations was performed by OEDocking 3.2.0.2 software. The binding potential assessment revealed that thiourea derivatives of naproxen exhibited a comparable binding affinity as naproxen towards COX-2. The highest number of key binding interactions with 5-LOX was formed by compound 5, whereas compound 6 established the most stable complex (-9.29 kcal/mol). According to the obtained results, derivatives 5 and 6 can be considered as dual COX-2/5-LOX inhibitors with potential anti-inflammatory activity. However, none of the investigated compounds were able to form three hydrogen bonds with the binding site of COX-2, as well as three key hydrogen bonds with the active site of 5-LOX

Investigation of binding mode of isoamyl derivative of thiosalicylic acid and human serum albumin

Thiosalicylic acid is known for its diverse pharmacological properties and its frequent use in various synthetic conversions. The unique structure of thiosalicylic acid permits the incorporation of diverse S-alkyl derivatives, resulting in favorable chemical characteristics for numerous applications. Therefore, affinity for one of the binding sites of human serum albumin (HSA) of isoamyl derivative of thiosalicylic acid (ligand, L), were examined. Binding mode of compound L was determined using fluorescence spectroscopy. Warfarin was used as a marker for Sudlow’s Site I (subdomain IIA), while ibuprofen was used as a marker for Sudlow’s Site II (subdomain IIIA). Obtained values of Ka suggested that investigated compound bind to HSA. Results of site marker competitive experiments showed that the tested L bind to HSA in domain IIA (Site I). The presented results will help to improve the research of the mechanism of the interaction between transport proteins and similar compounds.https://sciforum.net/paper/view/15705Publishe

The interaction studies between isobutyl derivative of thiosalicylic acid and human serum albumin

It is well known that thiosalicylic acid and its S-alkyl derivatives have found applications in medicinal inorganic chemistry. Here are the study results on the interactions between the isobutyl derivatives of thiosalicylic acid (ligand, L) and human serum albumin (HSA). In particular, serum albumin is the primary soluble protein found in the human circulatory system. The metabolism of drugs, their distribution, and effectiveness strongly depend on the drug-albumin interaction. This interaction also affects the concentration of free drugs in the body. The interactions of the isobutyl derivatives of thiosalicylic acid (L) with HSA under physiological conditions was investigate by spectroscopy measurements and molecular docking. The results suggest that ligand could interact with HSA and influenced a slight change in the conformation of HSA through the static quenching mechanism. The analysis revealed that the HSA molecule has a moderate reaction to the ligand, as there is only one binding site for the ligand on the protein.https://sciforum.net/paper/view/15767Publishe

Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen

The objective of this study was to synthesize seven novel thiourea derivatives of naproxen (8–14), examine the anti-inflammatory activity of the newly synthesized compounds, investigate the cytotoxic potential of both sets of synthesized compounds (1–7 and 8–14), and select the most promising anti-inflammatory and antitumor drug candidates. The results of the in vivo anti-inflammatory study clearly showed that compounds 8 and 9 were capable of decreasing paw edema, as evident from a high percentage of inhibition (44.83% and 49.29%, respectively). In addition, the results of in vitro enzyme inhibition assays demonstrated that neither of the newly synthesized compounds reached 50% inhibition of 5-LOX at concentrations lower than 100 μM. In terms of antitumor potential, derivatives 3 and 8 exhibited strong cytotoxic effects on the HeLa cell line, suggesting the involvement of the extrinsic pathway of apoptosis. According to the overall results obtained for both sets of synthesized molecules, derivatives 4 and 8 can be underlined as molecules with the strongest anti-inflammatory activity, while derivatives 3 and 8 are the most promising cytotoxic agents

Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen

The aim of the study was a synthesis and investigation of the dose-dependent anti-inflammatory effect of new thiourea derivatives of naproxen with selected aromatic amines and esters of aromatic amino acids. The results of the in vivo study indicate that derivatives of m-anisidine (4) and N-methyl tryptophan methyl ester (7) showed the most potent anti-inflammatory activity four hours after injection of carrageenan, with the percentage of inhibition of 54.01% and 54.12%, respectively. In vitro assays of COX-2 inhibition demonstrated that none of the tested compounds achieved 50% inhibition at concentrations lower than 100 µM. On the other hand, the aromatic amine derivatives (1–5) accomplished significant inhibition of 5-LOX, and the lowest IC50 value was observed for compound 4 (0.30 μM). High anti-edematous activity of compound 4 in the rat paw edema model, together with potent inhibition of 5-LOX, highlight this compound as a promising anti-inflammatory agen

Selected thiourea derivatives of naproxen as potential anti-inflammatory agents: in vivo, in vitro, and in silico approach

The aim of the conducted study was to develop new potential dual COX-2 and 5-LOX inhibitors based on naproxen scaffold. We performed the evaluation of in vivo and in vitro anti-inflammatory activity of newly synthesized thiourea derivatives of naproxen containing m-anisidine and N-methyl tryptophan methyl ester in a side chain. An in vivo study was carried out using a carrageenan-induced paw edema model of acute inflammation. COX-2 and 5-LOX inhibitory potential of synthesized compounds was evaluated using fluorometric inhibitor screening kits. In silico study was performed in OEDocking 3.2.0.2 software with the FRED tool. Two investigated derivatives exhibited comparable anti-inflammatory activity to naproxen (56.32%) four hours after injection of carrageenan, with the percentage of inhibition being 54.01% (m-anisidine derivative) and 54.12% (N-methyl tryptophan methyl ester derivative). In vitro studies of COX-2 inhibition demonstrated that none of the tested compounds achieved 50% inhibition at concentrations below 100 μM, whereas the m-anisidine derivative accomplished comparable inhibition of 5-LOX (IC50 = 0.30 μM) to commercial 5-LOX inhibitor zileuton (IC50 = 0.36 μM). Inability of the tested compounds to form three hydrogen bonds with ARG120 and TYR355 could be a reason why these compounds showed weak COX-2 inhibition. The m-anisidine derivative formed a more stable complex with the 5-LOX enzyme (−8.39 kcal/mol), compared to N-methyl tryptophan methyl ester derivative (−7.98 kcal/mol), with the absence of the iron ion chelation in the active site in both cases. The significant in vivo anti-inflammatory activity of the m-anisidine derivative, together with the potent inhibition of 5-LOX, highlighted this compound as a promising anti-inflammatory agent

The pygidial gland secretion of Laemostenus punctatus (Coleoptera, Carabidae): a source of natural agents with antimicrobial, anti-adhesive, and anti-invasive activities

In the present study, we investigated in vitro the antimicrobial activity of the pygidial gland secretion of the guanophilic ground beetle Laemostenus (Pristonychus) punctatus (Dejean, 1828) and some of its chemicals against resistant and non-resistant bacteria and Candida species, the synergistic and additive potential of combinations of selected chemicals and antimicrobial drugs against resistant bacterial and fungal strains, anti-adhesive and anti-invasive potential of the secretion and formic acid alone and in selected combinations with antimicrobial drugs against methicillin-resistant Staphylococcus aureus (MRSA) toward spontaneously immortalized human keratinocyte cell line (HaCaT cells). In addition, we examined the antiproliferative activity of the secretion and formic acid in vitro. The tested secretion and the standards of formic and oleic acids possessed a significant level of antimicrobial potential against all tested strains (P < 0.05). The isolate from guano Pseudomonas monteilii showed the highest resistance to the secretion and formic acid, while MRSA achieved a significantly high level of susceptibility to all agents tested, particularly to the combinations of formic acid and antibiotics, but at the same time showed a certain level of resistance to the antibiotics tested individually. Candida albicans and C. tropicalis were found to be the most sensitive fungal strains to the secretion. Formic acid (MIC 0.0005 mg/mL) and gentamicin (MIC 0.0010 mg/mL) in the mixture achieved synergistic antibacterial activity against MRSA (FICI = 0.5, P < 0.05). The combination of formic acid, gentamicin and ampicillin accomplished an additive effect against this resistant bacterial strain (FICI = 1.5, P < 0.05). The secretion achieved a better inhibitory effect on the adhesion ability of MRSA toward HaCaT cells compared to formic acid alone, while formic acid showed better results regarding the invasion (P < 0.001). The combinations of gentamicin and ampicillin, as well as of formic acid and gentamicin and ampicillin achieved similar anti-adhesive and anti-invasive effects, with a slight advantage of formic acid and antibiotics in combination (P < 0.001). The secretion and formic acid were found to be non-toxic to HaCaT cells in vitro (IC50 ≥ 401 μg/mL)

Pygidial gland secretions of Carabus Linnaeus, 1758 (Coleoptera: Carabidae): chemicals released by three species

It is a commonly known fact that all ground beetles possess abdominal pygidial glands with relatively similar gross structure and function among species. Still, morphology of the glands and composition of their secretions have not been studied in most ground beetle species. These exocrine glands and their products are mainly associated with defence in natural environments. In this paper, we studied three predatory ground beetle species of the genus Carabus Linnaeus, 1758, namely C. (Archicarabus) montivagus Palliardi, 1825, C. (Megodontus) caelatus Fabricius, 1801, and C. (M.) violaceus Linnaeus, 1758, to identify chemical components of their pygidial gland secretions. Altogether, 10 carboxylic acids were isolated from the analysed secretions [two from the secretion of C. (A.) montivagus, 10 from that of C. (M.) caelatus, and nine from that of C. (M.) violaceus]. The finding of 2-hexenoic acid in the secretion of C. (M.) caelatus is the first finding of it within the entire subfamily Carabinae. In addition, we also analysed the morphology of glands of the species C. (M.) violaceus

Pygidial glands of three ground beetle taxa (Insecta, Coleoptera, Carabidae): a study on their morphology and chemical composition of their secretions

Morphology of the pygidial glands and chemical compositions of their secretion were analysed in the adults of three selected ground beetle taxa. Secretions of pygidial glands of Cychrus (Cychrus) semigranosus, Patrobus atrorufus and Pterostichus (Platysma) niger were chemically tested. Additionally, pygidial glands of the latter two species were investigated using bright-field microscopy and nonlinear microscopy and morphological features of the glands were described in detail. Both C. (C.) semigranosus and P. atrorufus were studied for the first time in terms of chemical ecology, while the latter species was analysed for the first time in terms of pygidial gland morphology. Altogether, eight compounds were detected in the dichloromethane extracts of the pygidial gland secretions of the three ground beetle taxa analysed. The simplest secretion mixtures were present in C. (C.) semigranosus and P. atrorufus (with two compounds each), while the extract of P. (P.) niger contained five compounds. The presence of 1-tetradecanol in the secretion of P. (P.) niger represents the first finding of this compound from the pygidial gland secretion extracts of ground beetles