2,4,5-Trichloro-6-((2,4,6-trichlorophenyl)amino)isophthalonitrile, Exerts Anti-bladder Activities through IGF-1R/STAT3 Signaling.

2,4,5-Trichloro-6-((2,4,6-trichlorophenyl)amino)isophthalonitrile (SYD007) is a small molecule compound that was synthesized according to the structure of diarylamine. In this study, we evaluated the anti-bladder activities of SYD007, and determined its cytotoxic mechanism. We found that SYD007 exerted cytotoxicity to bladder cancer cells. Furthermore, SYD007 induced bladder cancer cell early apoptosis and arrested cell cycle. Mechanistically, SYD007 suppressed phosphorylated signal transducer and activator of transcription 3 (p-STAT3) (Tyr705) level in parallel with increases of p-extracellular signal-regulated kinase (ERK) and p-AKT. SYD007 significantly inhibited insulin-like growth factor 1 (IGF-1)-induced STAT3 activation through down-regulation of total IGF-1R level. No dramatic changes in IGF-1R mRNA levels were observed in SYD007-treated cells, suggesting that SYD007 acted primarily at a posttranscriptional level. Using molecular docking analysis, SYD007 was identified as an IGF-1R inhibitor. In summary, we reported that SYD007 exerted anti-bladder activities, and these effects were partially due to inhibition of IGF-1R/STAT3 signaling.

B2, an abscisic acid mimic, improves salinity tolerance in winter wheat seedlings via improving activity of antioxidant enzymes.

Salinity severely inhibits growth and reduces yield of salt-sensitive plants like wheat, and this effect can be alleviated by plant growth regulators and phytohormones, among which abscisic acid (ABA) plays a central role in response to various stressful environments. ABA is highly photosensitive to light disruption, which this limits its application. Here, based on pyrabactin (a synthetic ABA agonist), we designed and synthesized a functional analog of ABA and named B2, then evaluated its role in salt resistance using winter wheat seedlings. The phenotypes showed that B2 significantly improved the salt tolerance of winter wheat seedlings by elevating the biomass. The physiological analysis found that B2 treatment reduced the generation rate of O2 -, electrolyte leakage, the content of proline, and the accumulation of malonaldehyde (MDA) and H2O2 and also significantly increased the contents of endogenous hormones zeatin riboside (ZA) and gibberellic acid (GA). Further biochemical analysis revealed that the activities of various antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX), were enhanced by B2, and the activities of antioxidase isozymes SOD3, POD1/2, and APX1/2 were particularly increased, largely resembling ABA treatment. The abiotic stress response-related gene TaSOS1 was significantly upregulated by B2, while the TaTIP2;2 gene was suppressed. In conclusion, an ABA analog B2 was capable to enhance salt stress tolerance in winter wheat seedlings by stimulating the antioxidant system, providing a novel regulator for better survival of crops in saline soils and improving crop yield.

Computational and Experimental Investigation of the Selective Adsorption of Indium/Iron Ions by the Epigallocatechin Gallate Monomer.

Selective recovery of indium has been widely studied to improve the resource efficiency of critical metals. However, the interaction and selective adsorption mechanism of indium/iron ions with tannin-based adsorbents is still unclear and hinders further optimization of their selective adsorption performance. In this study, the epigallocatechin gallate (EGCG) monomer, which is the key functional unit of persimmon tannin, was chosen to explore the ability and mechanism of selective separation/extraction of indium from indium-iron mixture solutions. The density functional theory calculation results indicated that the deprotonated EGCG was easier to combine with indium/iron cations than those of un-deprotonated EGCG. Moreover, the interaction of the EGCG-Fe(III) complex was dominated by chelation and electrostatic interaction, while that of the EGCG-In(III) complex was controlled by electrostatic interactions and aromatic ring stacking effects. Furthermore, the calculation of binding energy verified that EGCG exhibited a stronger affinity for Fe(III) than that for In(III) and preferentially adsorbed iron ions in acidic or neutral solutions. Further experimental results were consistent with the theoretical study, which showed that the Freundlich equilibrium isotherm fit the In(III) and Fe(III) adsorption behavior very well, and the Fe(III) adsorption processes followed a pseudo-second-order model. Thermodynamics data revealed that the adsorption of In(III) and Fe(III) onto EGCG was feasible, spontaneous, and endothermic. The adsorption rate of the EGCG monomer for Fe(III) in neutral solution (1:1 mixed solution, pH = 3.0) was 45.7%, 4.3 times that of In(III) (10.7%). This study provides an in-depth understanding of the relationship between the structure of EGCG and the selective adsorption capacity at the molecular level and provides theoretical guidance for further optimization of the selective adsorption performance of structurally similar tannin-based adsorbents.

Computational Analysis on Antioxidant Activity of Four Characteristic Structural Units from Persimmon Tannin.

Antioxidants are molecules that can prevent the harmful effects of oxygen, help capture and neutralize free radicals, and thus eliminate the damage of free radicals to the human body. Persimmon tannin (PT) has excellent antioxidant activity, which is closely related to its molecular structure. We report here a comparative study of four characteristic structural units from PT (epicatechin gallate (ECG), epigallocatechin gallate (EGCG), A-type linked ECG dimer (A-ECG dimer), A-type linked EGCG dimer (A-EGCG dimer)) to explore the structure-activity relationship by using the density functional theory. Based on the antioxidation mechanism of hydrogen atom transfer, the most favorable active site for each molecule exerts antioxidant activity is determined. The structural parameters, molecular electrostatic potential, and frontier molecular orbital indicate that the key active sites are located on the phenolic hydroxyl group of the B ring for ECG and EGCG monomers, and the key active sites of the two dimers are located on the phenolic hydroxyl groups of the A and D' rings. The natural bond orbital and bond dissociation energy of the phenolic hydroxyl hydrogen atom show that the C11-OH in the ECG monomer and the C12-OH in the EGCG monomer are the most preferential sites, respectively. The most active site of the two A-linked dimers is likely located on the D' ring C20' phenolic hydroxyl group. Based on computational analysis of quantum chemical parameters, the A-ECG dimer is a more potent antioxidant than the A-EGCG dimer, ECG, and EGCG. This computational analysis provides the structure-activity relationship of the four characteristic units which will contribute to the development of the application of PT antioxidants in the future.

Enantioselective induction of a glutathione-S-transferase, a glutathione transporter and an ABC transporter in maize by Metolachlor and its (S)-isomer.

The metabolism of chiral herbicides in plants remains poorly understood. Glutathione conjugation reactions are one of the principal mechanisms that plants utilize to detoxify xenobiotics. The induction by rac- and S-metolachlor of the expression of three genes, ZmGST27, ZmGT1 and ZmMRP1, encoding respectively a glutathione-S-transferase, a glutathione transporter and an ATP-binding cassette (ABC) transporter was studied in maize. The results demonstrate that the inducing effect of rac- and S-metolachlor on the expression of ZmGST27 and ZmGT1 is comparable. However, the inducing effect of rac-metolachlor on ZmMRP1 expression is more pronounced than that of S-metolachlor. Furthermore, vanadate, an ABC transporter inhibitor, could greatly reduce the difference in herbicidal activity between rac- and S-metolachlor. These results suggest that the ABC transporters may preferentially transport conjugates of rac-metolachlor, leading to a faster metabolism of the latter. Through comparing the expression of ZmGST27, ZmMRP1 and ZmGT1 after treatment by rac- and S-metolachlor, we provide novel insights into the metabolic processes of chiral herbicides in plants.