Study on in vitro Toxicity of Biometal(II) Monensinates Against Rat Zajdela Liver Tumour

The ability of Monensic acid A (MonH∙H2O) and its neutral metal complexes [M(Mon)2(H2O)2]with ions of Mg2+, Ca2+, Mn2+, Co2+, Ni2+ and Zn2+ to decrease viability and proliferation of primary cell cultures, originating from a chemically induced transplantable liver tumour of Zajdela in rats, and bone marrow cells from the same tumour-bearers, was evaluated. Experimental data revealed that manganese(II) and nickel(II) complexes of Monensin A are relatively more selective against the tumour as compared to the healthy bone marrow cells.

Stereoselective Synthesis of 1,6,9-Tri-oxaspiro[4.5]decanes From d-Glucose: Novel Structural Motifs of Spiroacetal Natural Products

Spiroacetals are the central structural core element of numerous natural products and are essential for their biological activity. A typical structural representative of a spiroacetal is the bicyclic 1,6-dioxaspiro[4.5]decane ring system. It represents the complete or partial structure of many biologically potent natural products such as the Paravespula pheromone 1, the antibiotic (+)-monensin A 2, the anticancer agent (−)-berkelic acid 3, the antimitotic ingredient spirastrellolide F, characterized after methylation as (+)-methyl ester 4, and the marine toxin (−)-calyculin A 5. In these compounds, the 1,6-dioxaspiro[4.5]decane ring system is found in either spiro ( R)-6 or ( S) - 6 configuration. The corresponding 1,6,9-trioxaspiro[4.5]decane framework ( S)-7 and ( R)-7 with opposite chirality at the spiro center due to an additional oxygen atom at position 9 in the pyran portion has so far not been found in living organisms or been synthesized. To close this gap and enable structure–activity relationship studies, potentially leading to novel antibiotics and selective anticancer agents, we have developed an efficient and stereocontrolled route to the ( R)- and ( S)-configurated 1,6,9-trioxaspiro[4.5]decane ring system leading to oxa analog motifs of the above natural products.

Biological Redox Impact of Tocopherol Isomers Is Mediated by Fast Cytosolic Calcium Increases in Living Caco-2 Cells

Most of the biological impacts of Vitamin E, including the redox effects, have been raised from studies with α-tocopherol only, despite the fact that tocopherol-containing foods carry mixed tocopherol isomers. Here, we investigated the cellular mechanisms involved in the immediate antioxidant responses evoked by α-, γ- and δ-tocopherol in Caco-2 cells. In order to track the cytosolic redox impact, we performed imaging on cells expressing HyPer, a fluorescent redox biosensor, while cytosolic calcium fluctuations were monitored by means of Fura-2 dye and imaging. With this approach, we could observe fast cellular responses evoked by the addition of α-, γ- and δ-tocopherol at concentrations as low as 2.5 μM. Each isomer induced rapid and consistent increases in cytosolic calcium with fast kinetics, which were affected by chelation of extracellular Ca2+, suggesting that tocopherols promoted a calcium entry upon the contact with the plasma membrane. In terms of redox effects, δ-tocopherol was the only isomer that evoked a significant change in the HyPer signal at 5 μM. By mimicking Ca2+ entry with ionomycin and monensin, a decline in the HyPer signal was induced as well. Finally, by silencing calcium with 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA), an intracellular Ca2+ chelator, none of the isomers were able to induce redox changes. Altogether, our data indicate that an elevation in cytoplasmic Ca2+ is necessary for the development of a tocopherol-induced antioxidant impact on the cytoplasm of Caco-2 cells reported by HyPer biosensor.

Factors governing the competition between group IA and IB cations for monensin A: a DFT/PCM study

The results obtained suggest that the metal selectivity of monensin can be modulated by changing the solvents used.

PSXIV-9 Effect of monensin, a blend of essential oils and Lithothamnium calcareum over two racial groups in finishing cattle diets

This study aimed the evaluation of the effects of three feed additives – sodium monensin (MON; 32 mg/kg DM), Lithothamnium calcareum plus sodium monensim (LC+MON; LithoNutri® 5g/kg DM + 32 mg/kg DM) or a blend of essential oils (BEO; BioPhitus® 0.3g/kg DM) – and its interaction with two ratial groups of beef cattle – Nellore (NEL) vs. Crossbreds (CROSS) – on a finishing diet. Ninety Nellore bulls (initial BW = 394 ± 34 kg) and ninety crossbreds (initial BW = 406 ± 31 kg), were fed for 112 days, diets containing 8.5% sugarcane bagasse, 42.2% of fine ground corn, 41.7% of citrus pulp, 5% of soybean meal, 1.3% of urea, 0.35% of sodium chloride and 0.95% of minerals and vitamins. Treatments were NEL+MON; NEL+LC+MON; NEL+BEO; CROSS+MON; CROSS+LC+MON; CROSS+BEO in a randomized complete block with a 2 x 3 factorial arrangement (2 racial groups and 3 feed additives). There were no interactions between racial groups and feed additives (P > 0.05). Regardless of the additive used there were no differences in final BW (P = 0.237), ADG (P = 0.610), HCW (P = 0.120) or dressing (P = 0.095). Animals fed LC+MON had lower DMI (P < 0.01) than animals fed MON or BEO (7.74 kg, 8.64 kg, 9.26 kg, respectively). However, feed efficiency (G:F) of LC+MON did not differ from MON. Animals fed diets with BEO had lower G:F than animals fed diets with MON or LC+MON (P < 0.01; 0.1382, 0.1469 and 0.1550 respectively). Animals fed diets with MON or LC+MON were 6.3% and 12% more efficient than animals fed with BEO. Crossbred bulls had higher DMI (P < 0.001), ADG (P < 0.001), FBW (P < 0.001) and HCW (P < 0.001) than Nellore bulls. In summary, LC reduced DMI not altering feed efficiency. Diets containing BEO reduced G:F of the animals when compared with animals receiving diets containing MON.

Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial Drugs

Actinomycetes are remarkable producers of compounds essential for human and veterinary medicine as well as for agriculture. The genomes of those microorganisms possess several sets of genes (biosynthetic gene cluster (BGC)) encoding pathways for the production of the valuable secondary metabolites. A significant proportion of the identified BGCs in actinomycetes encode pathways for the biosynthesis of polyketide compounds, nonribosomal peptides, or hybrid products resulting from the combination of both polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs). The potency of these molecules, in terms of bioactivity, was recognized in the 1940s, and started the “Golden Age” of antimicrobial drug discovery. Since then, several valuable polyketide drugs, such as erythromycin A, tylosin, monensin A, rifamycin, tetracyclines, amphotericin B, and many others were isolated from actinomycetes. This review covers the most relevant actinomycetes-derived polyketide drugs with antimicrobial activity, including anti-fungal agents. We provide an overview of the source of the compounds, structure of the molecules, the biosynthetic principle, bioactivity and mechanisms of action, and the current stage of development. This review emphasizes the importance of actinomycetes-derived antimicrobial polyketides and should serve as a “lexicon”, not only to scientists from the Natural Products field, but also to clinicians and others interested in this topic.