New cytotoxic natural products from the mangrove biome: covering the period 2007–2015

<p>Nowadays, the mangrove biome is considered to be a profound resource of natural products usually possessing cytotoxicity of a broader range. Covering the period 2007–2015, a total of 21 new naturally occurring compounds has stood out. For example, xylogranin B and swietephragmin C were found to exhibit very potent cytotoxic activity against the colon HCT-116 cells reaching IC₅₀ values of 0.05 and 0.06 μM, respectively. Bearing in mind the efficacy of the majority compounds in the preliminary <i>in vitro</i> screens, these studies should be expanded to both <i>ex vivo</i> and <i>in vivo</i> screens including the evaluation of the relevant toxicological profiles.</p

An insight into the cytotoxic activity of phytol at <i>in vitro</i> conditions

<div><p>The cytotoxicity of the diterpene alcohol, phytol, was evaluated by using the MTT assay <i>in vitro</i> against seven tumour cells and one normal cell of human origin. The compound tested induced concentration-dependent cytotoxic response in all cell lines, demonstrating to be most and least effective against the breast adenocarcinoma MCF-7 and the prostate adenocarcinoma PC-3 cells, respectively (IC₅₀ 8.79 ± 0.41 μM and 77.85 ± 1.93 μM). The IC₅₀ values towards the other five tumours (HeLa, HT-29, A-549, Hs294T and MDA-MB-231) ranged from 15.51 to 69.67 μM. However, mild toxicity was detected against the foetal lung fibroblast MRC-5 cells at the concentrations used (IC₅₀ 124.84 ± 1.59 μM). According to the experimental data obtained, this cost-effective natural product widely present in the biosphere may inspire the development of new drug-like substances with improved cytotoxic activity on breast cancer.</p></div

<i>In vitro</i> avarol does affect the growth of <i>Candida</i> sp.

<p>This work extends <i>in vitro</i> screening of antimicrobial activity of avarol, the marine natural product firstly isolated from the Mediterranean sponge <i>Dysidea avara</i>. Its anticandidial activity was evaluated by microdilution method against eight <i>Candida</i> strains, two ATCC and six clinical ones. At a different extent this compound was proven to be active against all the strains tested (MIC 0.8–6.0 μg/mL and MFC 1.6–12.0 μg/mL, respectively). According to the best of our knowledge, this is the first report on avarol activity towards any yeast strain which may be of relevance for Alzheimer’s disease. Indeed, avarol derivatives showing moderate AChE activity should be screened for anticandidial activity both <i>in vitro</i> and <i>in vivo</i>.</p

<i>In vitro</i> anti-quorum sensing activity of phytol

<div><p>Anti-quorum sensing activity of the diterpene phytol was evaluated <i>in vitro</i> for the first time. This compound (at three sub-MIC concentrations – 0.5, 0.25 and 0.125 MIC, respectively) reduced the formation of <i>Pseudomonas aeruginosa</i> PAO1 biofilm in the range of 74.00–84.33% exhibiting higher activity than the both positive controls used, streptomycin and ampicillin. Phytol (0.5 MIC) also effectively reduced <i>P. aeruginosa</i> twitching and flagella motility. Indeed, the bacteria treated were incapable of producing a twitching zone and had almost round, smooth and regular colony edges. Finally, the tested compound (0.5 MIC) exhibited good <i>P. aeruginosa</i> pyocyanin inhibitory activity (51.94%) practically to the same extent as streptomycin (52.09%). According to the experimental data obtained, this phytol property may inspire design of medical foods targeting <i>P. aeruginosa</i> quorum sensing activity.</p></div

Anti-hydroxyl radical activity, redox potential and anti-AChE activity of <i>Amanita strobiliformis</i> polysaccharide extract

<p>This study outlines antioxidant and anti-AChE activities of the polysaccharide (PSH) extract from the mushroom species <i>Amanita strobiliformis</i>. Both the presence of α and ß glucans within the aforementioned extract was recorded. PSH extract displayed a profound scavenging activity of OH radicals (IC₅₀ value, 11.86 ± 0.59 μg/mL) and high potential for reduction of Fe³⁺ ions (174.11 ± 8.70 mg eq. AA/g d.w.) being almost 48- and 5-fold more effective than mannitol and butylated hydroxytoluene used as a positive control, respectively. Compared with galanthamine (0.001 μg), the same extract exhibited a moderate anti-AChE activity (10 μg) <i>in solid</i>. Since purified PSH extract exhibited higher bioactivity (IC₅₀ value 7.27 ± 0.31 μg/mL, 197.68 ± 9.47 mg eq. AA/g d.w. and 0.1 μg, respectively), it can be predominantly ascribed to the polysaccharide compounds. <i>A. strobiliformis</i> PSH extract may be considered as a promising resource of potent bioactive polysaccharides of natural origin successfully addressing both oxidative stress and lack of acetylcholine.</p

A contribution to pharmaceutical biology of freshwater sponges

<p><i>In vitro</i> anti-tumour and anti-radical activities of the acetone extract of the freshwater sponge <i>Ochridaspongia rotunda</i> were the subject of this study. The extract was found to be highly cytotoxic to human lung tumour cell line A-549 reaching IC₅₀ value of 5.01 ± 0.21 μg/mL. Indeed, it displayed only 2-fold less anti-tumour activity than doxorubicin (IC₅₀ value 2.42 ± 0.13 μg/mL) used as a positive control. The same extract was also found to be almost 37-fold more selective against A-549 vs. MRC-5 (normal) lung cells, in difference to weak selectivity of doxorubicin (less than 3-fold). Its profound anti-DPPH radical activity comparable to that of quercetin (IC₅₀ values 3.68 ± 0.19 and 3.14 ± 0.09 μg/mL, respectively) coupled with no signs of genotoxicity in the comet assay (MRC-5 cell line, vs. doxorubicin) has actually implicated the importance of this animal bioresource in searching for pharmaceutically useful bioactive compounds of natural origin.</p

The redox couple avarol/avarone in the fight with malignant gliomas: the case study of U-251 MG cells

<p>This study aimed to screen <i>in vitro</i> antitumour activity of the redox couple avarol/avarone against the human malignant glioma cell line U-251 MG for the first time. Compared both with avarol and positive controls used (temozolomide and doxorubicin), avarone was found to be the most active compound with IC₅₀ value below 1 μM (IC₅₀ 0.68 ± 0.04 μM, 96 h). Considerable less DNA damage in the cells treated with avarol and avarone vs. doxorubicin (105 & 123% vs. 299%, respectively; untreated U-251 MG cells were used as a control, 100%), coupled with no sign of cytotoxicity against the normal human foetal lung fibroblast MRC-5 cells (IC₅₀ > 100 μM), has actually pointed out the importance of this marine sesquiterpenoid quinone structure as a promising lead compound in development of novel brain chemotherapeutics.</p

Phenolic natural products of the wines obtained from three new Merlot clone candidates

<p>This work aimed to evaluate the total contents of polyphenolics (the Ribereau-Gayon–Maurié procedure), anthocyanins (using pH differential method) and tannins (the Nègre procedure) as well as the content of phenolic acids (using UPLC/MS chromatography), respectively of the wines obtained from three new Merlot clone candidates in the perennial clonal selection. The aforementioned chemical parameters were determined in the samples covering the period 2009–2012. In comparison both with the standard Merlot wine (mother vine) and the wines obtained from other two clone candidates, the Merlot wine of the clone candidate No. 022 was found to have the highest total content of all three examined components 1.89 ± 0.05 g/L (polyphenolics), 185.59 ± 5.00 mg/L (anthocyanins) and 1.11 ± 0.03 g/L (tannins), as well as six phenolic acids including gallic acid (25.49 ± 0.27 mg/L). These findings are in good agreement with the observed trend for the viticultural parameters indicating the clone candidate No. 022 as more promising than mother.</p

A bryozoan species may offer novel antioxidants with anti-carbon-dioxide anion radical activity

<div><p>The antiradical activity of the freshwater bryozoan <i>Hyalinella punctata</i> water extracts (two samples, seasonal collection) was evaluated by using electron paramagnetic resonance spectroscopy against hydroxyl (√OH), superoxide anion (√O₂⁻), methoxy (√CH₂OH), carbon-dioxide anion (√CO₂⁻), nitric-oxide (√NO) and 2,2-diphenyl-1-picrylhydrazyl (√DPPH) radicals. The extracts reduced the production of all tested radicals but to a varying degree. The better activity was observed against √CO₂⁻ and √CH₂OH radicals (54 ± 5% and 44 ± 4%, and 58 ± 6% and 22 ± 2%, respectively) than towards √DPPH, √NO, √OH and √O₂⁻ radicals (59 ± 6% and 1.0 ± 0.1%, 46 ± 5% and 14 ± 1%, 7.0 ± 0.5% and 34 ± 3%, and 33 ± 3% and 0%, respectively). FTIR spectra of the both extracts indicate the presence of cyclic peptides and polypeptides which might be responsible for the observed activity. According to the experimental data obtained, <i>H. punctata</i> water extract may be considered as a novel promising resource of natural products with anti √CO₂⁻ radical activity.</p></div

<i>In vitro</i> evaluation of cytotoxic and mutagenic activity of avarol

<p>The cytotoxicity of avarol, a main secondary metabolite of the Mediterranean sponge <i>Dysidea avara</i>, was <i>in vitro</i> screened by MTT assay against four human tumour cell lines. The colon HT-29 tumour cells practically showed to be the only sensitive ones towards this organic compound. No toxicity was found against the fetal lung fibroblast MRC-5 cells at the concentrations tested. In comparison with doxorubicin, used as a positive control, avarol actually exhibited at least 588-fold less toxicity towards normal MRC-5 cells. Finally, comet assay indicated that DNA fragmentation was almost fivefold higher upon the treatment with doxorubicin, compared to avarol. The obtained results have actually confirmed that avarol scaffold may contribute to development of new cytostatics inspired by nature.</p