Mutagenic, genotoxic and cytotoxic studies of invasive corals Tubastraea coccinea and Tubastraea tagusensis.

The high diversity of species in the marine environment gives rise to compounds with unique structural patterns not found as natural products in other systems and with great potential for pharmacological, cosmetic and nutritional use. The genus Tubastraea (Class Anthozoa, Order Scleractinia, Family Dendrophylliidae) is characterized as a hard coral without the presence of zooxanthellae. In species of this genus alkaloids derived from the compound aplysinopsin with pharmacological activity are known. In Brazil T. coccinea and T. tagusensis are characterized as non-indigenous and invasive and are currently found along the Brazilian coast, from Santa Catarina to Bahia states. This study aims to analyze the mutagenic, cytotoxic and genotoxic potential of methanolic and ethanolic extracts from T. coccinea and T. tagusensis collected in Ilha Grande Bay, Rio de Janeiro state, Brazil. Bacterial reverse mutation assay on the standard strains TA97, TA98, TA100, TA102 and TA104, in vitro micronucleus formation test and colorimetric assays for cytotoxic signals on the cell lines HepG2 and RAW264.7 were used. We also synthesized an oxoaplysinopsin derivate alkaloid (APL01) for comparative purposes. No mutagenic (250; 312.5; 375; 437.5 and 500 µg/plate) or genotoxic (0.05; 0.5; 5.0; 50 and 500 µg/mL) effects were observed in any sample tested for all measured concentrations. Cytotoxic responses were observed for eukaryotic cells in all tested samples at 500 and 5000 µg/mL concentrations. Cytotoxicity found in the WST-1 assay was independent of the metabolism of substances present in samples compositions. The cytotoxicity observed in the LDH release assay depended on metabolism.

Pharmacological activity of novel 2-hydroxyacetophenone isatin derivatives on cardiac and vascular smooth muscles in rats.

Isatin (1H-indole-2,3 dione) is an endogenous compound with biological activities. Many of its derivatives have pharmacological effects, including inhibition of cyclic guanosine monophosphate levels in cardiac tissue; sedative-hypnotic profiles; anticonvulsant, analgesic, antithermic, and anti-inflammatory activities; and anxiolytic, antimicrobial, and proapoptotic effects. Carbamates derived from isatin have a vasorelaxant profile. This study investigated the activity of 2 novel 2-hydroxyacetophenone derivatives of isatin (named MB101 and MB130) on the contractility of rat aorta and papillary muscles. Both compounds induced a concentration-dependent relaxation (5-100 µM) in the endothelium-intact aorta that was abolished by N-nitro-L-arginine methyl ester. Atropine, a muscarinic receptor antagonist, significantly prevented vasodilatation of 100 µM MB101. In contrast, atropine caused no significant alteration in MB130-induced vasorelaxation. Naloxone, a nonselective opioid receptor antagonist, completely prevented the relaxing effect of MB101 and MB130 at all concentrations. In papillary muscles, only MB130 induced a significant depression, and this contractile response was not altered by propranolol and atropine. Both the compounds reduced systolic and diastolic pressures in a dose-dependent manner in anesthetized rats. The 2-hydroxyacetophenones produced direct effects on vascular tonus through either muscarinic or opioid pathways. MB130 produced cardiac depression by opioid receptors and bradykinin because pretreatment HOE140 or with naloxone, an antagonist of type-2, bradykinin were able to partially block the decrease in twitch amplitude in papillary muscles induced by MB130. These findings provide information for designing new strategies for the treatment of cardiovascular disorders.

Anti-inflammatory potential of invasive sun corals (Scleractinia: Tubastraea spp.) from Brazil: alternative use for management?

OBJECTIVES: The objective was to analyse the anti-inflammatory potential of the invasive coral species Tubastraea coccinea and Tubastraea tagusensis. METHODS: Methanolic extracts, fractions and synthesized compounds were evaluated for their anti-inflammatory ability, and their composition was elucidated through chemical analysis. KEY FINDINGS: The genus Tubastraea (Order Scleractinia, Family Dendrophylliidae) (known as sun corals) presents compounds with pharmacological value. The introduction of these azooxanthellate hard corals into Brazil, initially in Rio de Janeiro state, occurred through their fouling of oil and gas platforms from the Campos oil Basin. The two invasive species have successfully expanded along the Brazilian coast and threaten endemic species and biodiversity. The HPLC-MS and GC-MS data suggest the presence of aplysinopsin analogues (alkaloids). Anti-inflammatory activity was observed in all samples tested in in-vivo assays, especially in T. coccinea. The ethyl acetate fraction from this sample was more effective in in-vitro assays for anti-inflammatory activity. Depending on the concentration, this fraction showed cytotoxic responses. CONCLUSIONS: These species have potential pharmacological use, and considering their invasive nature, this study presents a potential alternative use, which may enhance the management of this biological invasion.

Isatins inhibit cyclooxygenase-2 and inducible nitric oxide synthase in a mouse macrophage cell line.

Isatin is a versatile compound with a diversity of effects. We designed to investigate the inhibitory effect of isatin derivatives on lipopolysaccharide/interferon-gamma-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins, production of prostaglandin E(2) (PGE(2)), nitric oxide (NO), tumor necrosis factor (TNF-alpha), and their capacity to scavenge NO. Isatins inhibit TNF-alpha production and iNOS and COX-2 protein expression resulting on reduced levels of NO and PGE(2). Our results indicate isatin and it derivatives as inhibitors of iNOS and COX-2 enzymes, which might be used as anti-inflammatory and antitumoral agents.

Silica nanoparticles doped with anthraquinone for lung cancer phototherapy.

In the present study, SiO2 nanoparticles functionalized with 3-(2-aminoethylamino)propyl group (SiNP-AAP) were used, for the first time, to covalently bond rose bengal (SiNP-AAP-RB) or 9,10-anthraquinone-2-carboxylic acid (SiNP-AAP-OCAq). The functionalized SiNP were characterized by: Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM); elemental analysis (CHN) for determination of the dye concentration; FTIR and UV-vis diffuse reflectance (DR-UV-vis) and a surface area study (BET). The functionalized SiNPs were applied in photodynamic therapy (PDT) against lung cancer cell lines. The evaluated cytotoxicity revealed 20-30% cell survival after 15min of PDT for both materials but the OCAq concentration was half of the RB nanomaterial. The phototoxicity was mainly related to oxidative stress generated in the cellular environment by singlet oxygen and by hydrogen abstraction as confirmed by the laser flash photolysis technique. The unprecedented results indicate that SiNP-AAP-OCAq is a possible system for promoting cell apoptosis by both type I and type II mechanisms.