[Effects of PES and 2,4-DCP on the Extracellular Polymeric Substances and Microbial Community of Anaerobic Granular Sludge].

The effects of polyether sulfone (PES) microplastics and 2,4-dichlorophenol (2,4-DCP) on the loosely-bound extracellular polymeric substances (LB-EPS) and tightly-bound EPS (TB-EPS) of anaerobic granular sludge were investigated. In addition, high-throughput sequencing technology was used to analyze the changes in the microbial community and gene functions in the anaerobic granular sludge. The results revealed that the chemical oxygen demand (COD) removal rates of the 2,4-DCP and PES+2,4-DCP experimental groups were 35% and 37%, which were 57% and 55% lower than that of the blank control group, while the COD removal rates of the PES experimental group remained around 90%. After the addition of the PES microplastics and 2,4-DCP, the protein and polysaccharide contents in the LB-EPS decreased compared with the control group, and the polysaccharide content in TB-EPS increased the least. In presence of the PES microplastics and 2,4-DCP, the activity of coenzyme F420 was inhibited. Through high-throughput sequencing, the microbial richness and diversity of the anaerobic granular sludge in the experimental group were reduced with the addition of the PES microplastics or 2,4-DCP. In the control group and the experimental group, the dominant bacteria at the phylum level were Proteobacteria (13.45%-44.47%), Firmicutes (6.86%-21.67%), and Actinobacteria (3.16%-18.11%). The abundance of ß-Proteobacteria in the PES+2,4-DCP experimental group was reduced by 15.28%, while the abundance of γ-Proteobacteria increased by 28.44% compared with the control group. Based on the phylogenetic investigation of the communities using the reconstruction of unobserved states (PICRUSt) analysis, it was found that in the experimental group with the PES microplastics or 2,4-DCP, the genes related to the sludge energy metabolism function were 0.25%-0.72% more than the control group; therefore, the abundance of genes related to the transport function group decreased significantly.

[Synthesis and anti-proliferative activity of fluoroquinolone (rhodanine unsaturated ketone) amide derivatives].

To discover novel antitumor rhodanine unsaturated ketones, a series of fluoroquinolone (rhodanine α, ß-unsaturated ketone) amine derivatives (5a-5r) were designed and synthesized with fluoroquinolone amide scaffold as a carrier. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS. The in vitro anti-proliferative activity against Hep-3B, Capan-1 and HL60 cells was evaluated by MTT assay. The results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. The SAR revealed that some compounds carrying aromatic heterocyclic rings or phenyl attached to an electron-withdrawing carboxyl or sulfonamide substituent were comparable to or better than comparison doxorubicin against Capan-1 cells. As such, it suggests that fluoroquinolone (rhodanine α, ß-unsaturated ketone) amines are promising leads for the development of novel antitumor fluoroquinolones or rhodanine analogues.

[Synthesis and anti-proliferative activity of fluoroquinolone C-3 fused heterocyclic α,ß-unsaturated ketones derived from ciprofloxacin].

To discover novel antitumor fluoroquinolone lead compounds from a rational modification for antibacterial fluoroquinolones, a fused heterocyclic ketone corresponding to thiazolo[2,3- b][1,2,4]triazolone used as a bioisosteric replacement of the C-3 carboxylic acid group of ciprofloxacin 1, and further modification by a Claisen condensation reaction with substituted benzaldehydes formed novel fluoroquinolone C-3 fuse heterocyclic α, ß-unsaturated ketones as the title compounds (6a-6r), separately. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS, and the in vitro anti-proliferative activity against human hepatoma Hep-3B cells, pancreatic Capan-1 cells and leukemia HL60 cells was evaluated by a MTT assay. The preliminary results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. In particular, compounds carrying an electron-withdrawing carboxyl (6k, 6m) or sulfonamide substituent (6q, 6r) attached to benzene ring were comparable to or better than constractive drug doxorubicin against Capan-1 cells. As such, it suggests that it is favorable for a fused heterocyclic α, ß-unsaturated ketone scaffold instead of the C-3 carboxylic acid group to improve the antitumor activity of fluoroquinolones.

[Synthesis and antitumor activity of fluoroquinolon-3-yl-s-triazole sulfide ketones and their derivatives from ciprofloxacin].

To discover an efficient strategy for the conversion of the antibacterial activity of fluoroquinolones into the antitumor activity, the three series of C-3 s-triazole-based derivatives including sulfide ketones (6a-6g), thiosemicarbazones (7a-7g) and fused heterocyclic thiazolotriazoles (8a-8g) were synthesized from ciprofloxacin (1), respectively. The structures were characterized by elemental analysis and spectral data. The antitumor activity was tested against three tumor cell lines (Hep-3B, Capan-1 and HL60) using the MTT assay. The three types of compounds all exhibited stronger anti-proliferative activities than ciprofloxacin in the test. The order of their activities was in compounds 7>8>6, and the order of selectivity against cancer cell lines was Capan-1, Hep-3B and HL60. Meanwhile, the SAR revealed that some compounds with electron-drawing group substituted such as fluoro- and nitro-phenyl compounds (6f, 7f, 8f) and (6g, 7g, 8g) displayed more significant activity than the control compounds, especially the IC50 values of thiosemicarbazone compounds 7f and 7g against Capan-1 was comparable to doxorubicin. Thus, a five-membered triazole as the C-3 bioisostere modified with the functionalized side-chain of sulfide-ketone thiosemicarbazone warrants special attention and further investigation.

Photodynamic effects of 5-aminolevulinic acid and its hexylester on several cell lines.

5-aminolevulinic acid (ALA) and its hexyl-ester (He-ALA) has shown promising results in photodynamic detection and therapy of tumors. In this work, the photodynamic effects of ALA and He-ALA on neuroblastoma cells, hepatoma cells and fibroblast cells were comparatively studied. With the detection of fluorescence emission spectra, protoporphyrin IX (PpIX) induced by ALA or He-ALA was observed in these three cell lines. Confocal laser scanning microscope showed the diffuse PpIX fluorescence in cytoplasm of neuroblastoma cells. The kinetics of PpIX accumulation were different in these three kinds of cells. The PpIX content in hepatoma cells and fibroblast cells continuously increased with the incubation time of drugs until 12 h, while in neuroblastoma cells the PpIX content saturated around 8 h after incubation with ALA or He-ALA. In addition, the PpIX concentration in neuroblastoma cells was obviously higher than that in hepatoma cells and fibroblast cells, indicating that the PpIX production is cell line dependent. When incubated with ALA and irradiated with light, near 90% neuroblastoma cells were destroyed, while for hepatoma cells and fibroblast cells the death rate was around 50%. The results demonstrate that neuroblastoma cells are more sensitive to ALA-PDT and the neuro-tumor cells may be well suited for the treatment of ALA mediated photosensitization. Comparing to ALA, He-ALA can reach the similar results concerned PpIX production and PDT damaging in all three kinds of cells but with 10 times lower incubation concentration, demonstrating that He-ALA has higher efficiency than ALA on inactivation of cancer cells in vitro.