Two new sponge species (Demospongiae: Chalinidae and Suberitidae) isolated from hyperarid mangroves of Qatar with notes on their potential antibacterial bioactivity.

This study presents the taxonomic description of two new sponge species that are intimately associated with the hyperarid mangrove ecosystem of Qatar. The study includes a preliminary evaluation of the sponges' potential bioactivity against pathogens. Chalinula qatari sp. nov. is a fragile thinly encrusting sponge with a vivid maroon colour in life, often with oscular chimneys and commonly recorded on pneumatophores in the intertidal and shallow subtidal zone. Suberites luna sp. nov. is a massive globular-lobate sponge with a greenish-black colour externally and a yellowish orange colour internally, recorded on pneumatophores in the shallow subtidal zone, with large specimens near the seagrass ecosystem that surrounds the mangrove. For both species, a drug extraction protocol and an antibacterial experiment was performed. The extract of Suberites luna sp. nov. was found to be bioactive against recognized pathogens such as Staphylococcus epidermidis, Staphylococcus aureus and Enterococcus faecalis, but no bioactive activity was recorded for Chalinula qatari sp. nov. This study highlights the importance of increasing bioprospecting effort in hyperarid conditions and the importance of combining bioprospecting with taxonomic studies for the identification of novel marine drugs.

Heavy metals accumulation from sewage sludge in the Nile tilapia Oreochromis niloticus (Trewavas, 1983) during a sludge-earthworm-fish short-term cycling.

Municipal sewage sludge from waste-water treatment is an important nutritional source for sustainable agriculture. Here, we report on the assessment of the accumulation of heavy metals in Nile tilapia Oreochromis niloticus (Trewavas 1983) fed on earthworms Eisenia fetida reared on soil treated with different concentrations of sewage sludge (25% and 100%) during sludge-earthworm-fish short-term cycling. In this short-term cycling the Nile tilapia collected from the White Nile were chosen as final consumers, whereas the earthworms reared on loam soil mixed with different ratios of sludge were used as a feed for the final consumers. Our results indicate that the concentrations of Cd2+, Cr2+, Pb2+ and Zn2+ in the sludge treated soil are proportional to the sludge content in the soil. Importantly, the accumulation of these heavy metals was significantly low in the earthworms and the Nile tilapia in comparison with the treated soil and that these concentrations in the Nile tilapia were below the international limits recommended by the US Environmental Protection Agency (2014). Moreover, the growth and overall flesh quality of the fish were improved as indicated by the growth increase up to 146% when fed on earthworm reared in 100% sludge. Additionally, our physico-chemical properties (i.e. pH, soil moisture, electric conductivity and organic matters) evaluation on the soil indicates an improvement of the soil quality when mixed with sewage sludge. These results suggest a sustainable application of sewage sludge in fish culture owing to its high nutritional values, low cost, and low risk of hazardous heavy metals when using primary consumers with heavy metals bioaccumulation capability such as E. fetida.

3-amino-benzo[d]isoxazoles as novel multitargeted inhibitors of receptor tyrosine kinases.

A series of benzoisoxazoles and benzoisothiazoles have been synthesized and evaluated as inhibitors of receptor tyrosine kinases (RTKs). Structure-activity relationship studies led to the identification of 3-amino benzo[ d]isoxazoles, incorporating a N, N'-diphenyl urea moiety at the 4-position that potently inhibited both the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor families of RTKs. Within this series, orally bioavailable compounds possessing promising pharmacokinetic profiles were identified, and a number of compounds demonstrated in vivo efficacy in models of VEGF-stimulated vascular permeability and tumor growth. In particular, compound 50 exhibited an ED 50 of 2.0 mg/kg in the VEGF-stimulated uterine edema model and 81% inhibition in the human fibrosarcoma (HT1080) tumor growth model when given orally at a dose of 10 mg/kg/day.

Post-harvest losses of fish in developing countries.

As the world population grows, increasing food supply becomes an evermore urgent priority. One vital aspect is the reduction of food loss after harvesting. For fish and seafood, being perishable, the situation is more crucial and the reduction in quantity and/or quality is enormous and difficult to estimate. The effort to reduce these after harvest losses must begin with a quantitative assessment of the problem. The low accuracy of loss survey techniques and limitation of extrapolating means stands against reliable economic estimation in undeveloped countries where greater and more effective losses exist. In the present paper, post-harvest losses were assessed with special emphasis on the following topics: Cultural and socioeconomic aspects including traditional food conservation; economic factors for food conservation and cost-benefit; assessment of the effect of globalization and liberalization of food markets and the fish trade in artisanal fisheries. Strategies for loss reduction included estimation of loss, education and training for individuals and the organizations actively involved in post-harvest food conservation.

Discovery of N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N'-(2-fluoro-5-methylphenyl)urea (ABT-869), a 3-aminoindazole-based orally active multitargeted receptor tyrosine kinase inhibitor.

In our continued efforts to search for potent and novel receptor tyrosine kinase (RTK) inhibitors as potential anticancer agents, we discovered, through a structure-based design, that 3-aminoindazole could serve as an efficient hinge-binding template for kinase inhibitors. By incorporating an N,N'-diaryl urea moiety at the C4-position of 3-aminodazole, a series of RTK inhibitors were generated, which potently inhibited the tyrosine kinase activity of the vascular endothelial growth factor receptor and the platelet-derived growth factor receptor families. A number of compounds with potent oral activity were identified by utilizing an estradiol-induced mouse uterine edema model and an HT1080 human fibrosarcoma xenograft tumor model. In particular, compound 17p (ABT-869) was found to possess favorable pharmacokinetic profiles across different species and display significant tumor growth inhibition in multiple preclinical animal models.

Thienopyridine urea inhibitors of KDR kinase.

A series of substituted thienopyridine ureas was prepared and evaluated for enzymatic and cellular inhibition of KDR kinase activity. Several of these analogs, such as 2, are potent inhibitors of KDR (<10 nM) in both enzymatic and cellular assays. Further characterization of inhibitor 2 indicated that this analog possessed excellent in vivo potency (ED50 2.1 mg/kg) as measured in an estradiol-induced mouse uterine edema model.

Isothiazolopyrimidines and isoxazolopyrimidines as novel multi-targeted inhibitors of receptor tyrosine kinases.

A series of isothiazolopyrimidines and isoxazolopyrimidines were synthesized and identified as potent KDR inhibitors. SAR studies led to isothiazolopyrimidine urea analogs that potently inhibit VEGFR tyrosine kinases (KDR enzymatic and cellular IC(50) values below 10 nM) as well as cKIT and TIE2. The selected compounds 8 and 13 display 56% and 48% oral bioavailability in mice, respectively.

Thienopyrimidine ureas as novel and potent multitargeted receptor tyrosine kinase inhibitors.

A series of novel thienopyrimidine-based receptor tyrosine kinase inhibitors has been discovered. Investigation of structure-activity relationships at the 5- and 6-positions of the thienopyrimidine nucleus led to a series of N,N'-diaryl ureas that potently inhibit all of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor tyrosine kinases. A kinase insert domain-containing receptor (KDR) homology model suggests that these compounds bind to the "inactive conformation" of the enzyme with the urea portion extending into the back hydrophobic pocket adjacent to the adenosine 5'-triphosphate (ATP) binding site. A number of compounds have been identified as displaying excellent in vivo potency. In particular, compounds 28 and 76 possess favorable pharmacokinetic (PK) profiles and demonstrate potent antitumor efficacy against the HT1080 human fibrosarcoma xenograft tumor growth model (tumor growth inhibition (TGI) = 75% at 25 mg/kg.day, per os (po)).

Isoindolinone ureas: a novel class of KDR kinase inhibitors.

A series of substituted isoindolinone ureas was prepared and evaluated for enzymatic and cellular inhibition of KDR kinase activity. Several of these analogs, such as 14c, are potent inhibitors of KDR both enzymatically (< 50 nM) and cellularly < or = 100 nM). A 3D KDR/CDK2/MAP kinase overlay model with several structurally related tyrosine kinase inhibitors was used to predict the binding interactions of the isoindolinone ureas with the KDR active site.