Marine Anticancer Agents: An Overview with a Particular Focus on Their Chemical Classes

The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve different pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more than 36,000 compounds have been isolated from marine micro- and macro-organisms including but not limited to fungi, bacteria, microalgae, macroalgae, sponges, corals, mollusks and tunicates, with hundreds of new marine natural products (MNPs) being discovered every year. Marine-based pharmaceuticals have started to impact modern pharmacology and different anti-cancer drugs derived from marine compounds have been approved for clinical use, such as: cytarabine, vidarabine, nelarabine (prodrug of ara-G), fludarabine phosphate (pro-drug of ara-A), trabectedin, eribulin mesylate, brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, belantamab mafodotin, plitidepsin, and lurbinectedin. This review focuses on the bioactive molecules derived from the marine environment with anticancer activity, discussing their families, origin, structural features and therapeutic use.     

Antioxidative activity of amino phospholipids and phospholipid/amino Acid mixtures in edible oils as determined by the Rancimat method

Phosphatidylethanolamine (PE), phosphatidylcholine (PC), lysine (Lys), and mixtures of them were tested for antioxidative activity in refined olive oil by the Rancimat method to investigate the role of the chemical reactions produced in the Rancimat vessel on the induction periods (IPs) obtained. PE and Lys, but not PC, increased the IPs of the oil when tested alone. In addition, PE/Lys and PC/Lys mixtures, but not PC/PE mixtures, exhibited a synergistic effect. All these results can be understood considering the in situ formation of oxidized lipid/amino compound reaction products with antioxidative activities. Thus, the formation of pyrroles could be detected after derivatization with p-(dimethylamino)benzaldehyde, and some of these compounds could be unambiguously identified by GC-MS after their conversion into volatile derivatives. In addition, the formed products contributed to the color developed, and a correlation was observed between the Rancimat IPs obtained and the yellowness index of the oxidized oils recovered from the Rancimat. Furthermore, the differences observed in the antioxidative activities of PE, PC, Lys, and their mixtures could be explained according to the lipophility and hydrophility of the oxidized lipid/amino compound reaction products formed. All these results suggest that chemical reactions are being produced in the Rancimat vessel and the Rancimat IPs obtained are a consequence of the antioxidative activities of the products formed in these reactions. Furthermore, Rancimat may be a valuable tool for testing antioxidative activities of antioxidants produced during food processing if favorable conditions for antioxidant formation are employed.     

Complexation of several fungicides with beta-cyclodextrin: determination of the association constants and isolation of the solid complexes

The formation of inclusion complexes with beta-cyclodextrin was studied for several popular fungicides of different types: prochloraz, 2-phenylphenol, thiophanate methyl, 8-hydroxyquinoline, and benalaxyl. Phase solubility diagrams showed that in all cases complexation takes place, leading to an important increase of water solubility in prochloraz and benalaxyl. Equilibrium association constants could be determined from the phase solubility data and from NMR titrations in the case of 2-phenylphenol. Because of the low solubility of the complex formed between 8-hydroxyquinoline and beta-cyclodextrin, the corresponding association constant could not be determined. The solid complexes of fungicide-cyclodextrin were prepared and isolated by different methods. The isolation of real complexes and not physical mixtures was confirmed in the cases of prochloraz, 2-phenylphenol, and benalaxyl by differential scanning calorimetry.     

Tequila authenticity assessment by headspace SPME-HRGC-IRMS analysis of 13C/12C and 18O/16O ratios of ethanol

By use of headspace SPME sampling and a PLOT column, on-line capillary gas chromatography-isotope ratio mass spectrometry was employed in the combustion (C) and the pyrolysis (P) modes (HRGC-C/P-IRMS) to determine the delta(13)C(VPDB) and delta(18)O(VSMOW) values of ethanol in authentic (n = 14) and commercial tequila samples (n = 15) as well as a number of other spirits (n = 23). Whereas with delta(13)C(VPDB) values ranging from -12.1 to -13.2 per thousand and from -12.5 to -14.8 per thousand similar variations were found for 100% agave and mixed tequilas, respectively, the delta(18)O(VSMOW) data differed slightly within these categories: ranges from +22.1 to +22.8 per thousand and +20.8 to +21.7 per thousand were determined for both the authentic 100% agave and mixed products, respectively. The data recorded for commercial tequilas were less homogeneous; delta(13)C(VPDB) data from -10.6 to -13.9 per thousand and delta(18)O(VSMOW) values from +15.5 to +22.7 per thousand were determined in tequilas of both categories. Owing to overlapping data, attempts to differentiate between white, rested, and aged tequilas within each of the two categories failed. In addition, discrimination of tequila samples from other spirits by means of delta(13)C(VPDB) and delta(18)O(VSMOW) data of ethanol was restricted to the products originating from C(3) as well as C(4)/CAM raw materials.     

Nutritional utilization by the rat of diets based on lentil (Lens culinaris) seed meal or its fractions

The nutritional effects in the rat of raw lentil meal or its fractions have been evaluated in three feeding trials. Growth, gain/feed ratio, apparent N digestibility, and N retention were significantly (p < 0.05) reduced by the inclusion of whole lentil meal, dehulled lentil meal, or ethanol-extracted lentil meal as the sole source of protein in the diet. Pure lentil lectin and lectin-depleted albumin proteins had no significant negative effect on nutritional performance. In contrast, growth, gain/feed ratio, protein conversion efficiency, N digestibility, and N retention were significantly (p < 0.05) reduced by diets containing lentil globulins or lentil hulls. The poor nutritional quality of raw lentil meal for rats is therefore likely to be primarily due to the combined effects of these two components.     

A new insight into the influence of habitat on the biochemical properties of three commercial sea cucumber species

International Aquatic Research - This work makes a comparative evaluation of the biochemical profile of three sea commercial cucumber species (Holothuria mammata, H. polii and H. tubulosa) caught...     

Molecular characterization of microalgae used in aquaculture with biotechnology potential

Microalgae are the main component of first tropic level in aquatic food chain; it is for this reason that they are used as food in aquaculture. Also due to its biotechnological potential properties, they are used in the production of diverse components, dyes, antioxidants, enzymes, emulsifiers, etc. The extended ways of microalgae applications require physiologically and genetically stable cultures as well as correctly identified organisms to guarantee reproducibility and reliability. But the variety of species and the morphological similarity between some of them make difficult the identification of some microalgae. The use of molecular markers has supplied a very useful tool for identification of microalgae in fast mode, such as in classification. The present study has worked on the molecular characterization of main species of microalgae used in aquaculture in base of the molecular markers 18S rRNA and 16S rRNA. Microalgae DNA has been amplified and sequenced, and the resultant sequences were analyzed and reflected in phylogenetic trees. The phylogenetic analyses obtained reflect as both molecular markers allow to differentiate the main genus used in aquaculture.     

Non‐invasive fast real‐time PCR assay for detection of the enteric parasite Enteromyxum scophthalmi in cultured turbot (Scophthalmus maximus L.)

Enteromyxum scophthalmi is a myxozoan parasite that causes severe parasitic diseases in cultured turbot affecting mainly the intestine of the host. It is characterized by producing acute enteritis, starvation and eventually death. Current diagnosis of E. scopthalmi use traditional techniques, based on the identification of the morphology of the parasite. These techniques take extended time to be carried out and do not favour the adoption of control measure at turbot farms and require the sacrifice of fish. This study develops a fast real‐time PCR molecular tool for the detection of E. scophthalmi in infected farmed turbot. This methodology is applicable for routine controls on the farm at every stage of the parasite infection. Results of the study demonstrate the robustness, specificity, efficiency and reliability of the technique. In addition, this study also provides a non‐invasive procedure of sampling through swaps. This allows control, prevention and diagnosis of the parasite infection at turbot farms while maintaining the welfare of the cultivated fish and avoiding sacrifice of the fish sampled.     

Precision phenotyping of imidazolinone-induced chlorosis in sunflower

Chlorosis level is a useful parameter to assess imidazolinone resistance in sunflower (Helianthus annuus L.). The aim of this study was to quantify chlorosis through two different methods in sunflower plantlets treated with imazapyr. The genotypes used in this study were two inbred lines reported to be different in their resistance to imidazolinones. Chlorosis was evaluated by spectrophotometrical quantification of photosynthetic leaf pigments and by a bioinformatics-based color analysis. A protocol for pigment extraction was presented which improved pigment stability. Chlorophyll amount decreased significantly when both genotypes were treated with 10 μM of imazapyr. Leaf color was characterized using Tomato Analyzer^® color test software. A significant positive correlation between color reduction and chlorophyll concentration was found. It suggests that leaf color measurement could be an accurate method to estimate chlorosis and infer chlorophyll levels in sunflower plants. These results highlight a strong relationship between imidazolinone-induced chlorosis and variations in leaf color and in chlorophyll concentration. Both methods are quantitative, rapid, simple, and reproducible. Thus, they could be useful tools for phenotyping and screening large number of plants when breeding for imidazolinone resistance in this species.     

Comparison of lignin and cellulose solubilities in ionic liquids by COSMO-RS analysis and experimental validation

In this work, the solubilities of lignin and cellulose in ionic liquids (ILs) have been analyzed and compared by COSMO-RS simulation. The excess enthalpy of the IL + lignin/cellulose mixtures is evaluated as reference property to describe the affinity of lignin and cellulose for different ionic liquids, in terms of the intermolecular interactions contributing to their mixing properties. Thus, the anion plays the main role in the dissolution process of both lignin and cellulose, in which the hydrogen bonding forces are the major interactions. The most promising anions for the cellulose and lignin dissolution are acetate, formate and chloride, whereas different cations can be employed. Computational results indicated that a rational combination of the anions and cations allows designing ILs able to dissolve with different selectivity lignin and cellulose. Some of these solutions are tested in the laboratory to validate the model employed and the regenerated solids are analyzed by FTIR spectroscopy.