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1.
Sci Total Environ ; 806(Pt 3): 151255, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-34710424

ABSTRACT

This study aimed to evaluate the influence of Eisenia fetida (Savigny), added to an acidic soil contaminated with potentially toxic elements (PTEs; As, Sb, Cd, Pb, Zn) and amended with a softwood-derived biochar (2 and 5% w/w), on the mobility of PTEs and soil health (i.e. nutrient availability, enzyme activity and soil basal respiration). The PTEs bioaccumulation by E. fetida and the acute ecotoxicity effects of the amended soils were also evaluated. The interaction between earthworms and biochar led to a significant increase in soil pH, organic matter, dissolved organic carbon content, cation exchange capacity, and exchangeable Ca compared to the untreated soil. Moreover, the water-soluble and readily exchangeable PTE fraction decreased (with the exception of Sb) between 1.2- and 3.0-fold in the presence of biochar and earthworms. Earthworms, biochar, and their combination, led to a reduction of phosphomonoesterase activity which in soils amended with biochar and earthworms decreased between 2.2- and 2.5-fold with respect to the untreated soil. On the other hand, biochar and earthworms also enhanced soil basal respiration and protease activity. Although the survival rate and the weight loss of E. fetida did not change significantly with the addition of 2% biochar, adding the highest biochar percentage (5%) resulted in a survival rate that was ~2-fold lower and a weight loss that was 2.5-fold higher than the other treatments. The PTE bioaccumulation factors for E. fetida, which were less than 1 for all elements (except Cd), followed the order Cd > As>Zn > Cu > Pb > Sb and were further decreased by biochar addition. Overall, these results highlight that E. fetida and biochar, especially at 2% rate, could be used for the restoration of soil functionality in PTE-polluted environments, reducing at the same time the environmental risks posed by PTEs, at least in the short time.


Subject(s)
Oligochaeta , Soil Pollutants , Animals , Charcoal , Soil , Soil Pollutants/analysis , Soil Pollutants/toxicity
2.
J Med Chem ; 58(23): 9309-33, 2015 Dec 10.
Article in English | MEDLINE | ID: mdl-26580420

ABSTRACT

A number of indole-3-glyoxylamides have previously been reported as tubulin polymerization inhibitors, although none has yet been successfully developed clinically. We report here a new series of related compounds, modified according to a strategy of reducing aromatic ring count and introducing a greater degree of saturation, which retain potent tubulin polymerization activity but with a distinct SAR from previously documented libraries. A subset of active compounds from the reported series is shown to interact with tubulin at the colchicine binding site, disrupt the cellular microtubule network, and exert a cytotoxic effect against multiple cancer cell lines. Two compounds demonstrated significant tumor growth inhibition in a mouse xenograft model of head and neck cancer, a type of the disease which often proves resistant to chemotherapy, supporting further development of the current series as potential new therapeutics.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Head and Neck Neoplasms/drug therapy , Indoles/chemistry , Indoles/therapeutic use , Tubulin Modulators/chemistry , Tubulin Modulators/therapeutic use , Animals , Antineoplastic Agents/pharmacokinetics , Caco-2 Cells , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/pathology , Heterografts , Humans , Indoles/pharmacokinetics , Male , Mice , Mice, Nude , Microtubules/drug effects , Microtubules/metabolism , Microtubules/pathology , Neoplasm Transplantation , Structure-Activity Relationship , Tubulin/metabolism , Tubulin/ultrastructure , Tubulin Modulators/pharmacokinetics
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