Design, synthesis and biological activity of novel triketone-containing quinoxaline as HPPD inhibitor.

BACKGROUND: 4-Hydroxyphenyl pyruvate dioxygenase (EC 1.13.11.27, HPPD) is one of the important target enzymes used to address the issue of weed control. HPPD-inhibiting herbicides can reduce the carotenoid content in plants and hinder photosynthesis, eventually causing albinism and death. Exploring novel HPPD-inhibiting herbicides is a significant direction in pesticide research. In the process of exploring new high-efficiency HPPD inhibitors, a series of novel quinoxaline derivatives were designed and synthesized using an active fragment splicing strategy. RESULTS: The title compounds were unambiguously characterized by infrared, 1 H NMR, 13 C NMR, and high-resolution mass spectroscopy. The results of the in vitro tests indicated that the majority of the title compounds showed potent inhibition of Arabidopsis thaliana HPPD (AtHPPD). Preliminary bioevaluation results revealed that a number of novel compounds displayed better or excellent herbicidal activity against broadleaf and monocotyledonous weeds. Compound III-5 showed herbicidal effects comparable to those of mesotrione at a rate of 150 g of active ingredient (ai)/ha for post-emergence application. The results of molecular dynamics verified that compound III-5 had a more stable protein-binding ability. Molecular docking results showed that compound III-5 and mesotrione shared homologous interplay with the surrounding residues. In addition, the enlarged aromatic ring system adds more force, and the hydrogen bond formed can enhance the synergy with π-π stacking. CONCLUSIONS: The present work indicates that compound III-5 may be a potential lead structure for the development of new HPPD inhibitors.

Design, Synthesis, and Bioevaluation of Substituted Phenyl Isoxazole Analogues as Herbicide Safeners.

Herbicide safeners enhance herbicide detoxification in crops without affecting target weed sensitivity. To enhance crop tolerance to the toxicity-related stress caused by the herbicide acetochlor (ACT), a new class of substituted phenyl isoxazole derivatives was designed by an intermediate derivatization method as herbicide safeners. Microwave-assisted synthesis was used to prepare the phenyl isoxazole analogues, and all of the structures were confirmed via IR, 1H NMR, 13C NMR, and HRMS. Compound I-1 was further characterized by X-ray diffraction analysis. Bioassay results showed that most of the obtained compounds provided varying degrees of safening against ACT-induced injury by increasing the corn growth recovery, glutathione content, and glutathione S-transferase activity. In particular, compound I-20 showed excellent safener activity against ACT toxicity, comparable to that of the commercial safener benoxacor. Gaussian calculations have been performed and the results indicated that the nucleophilic ability of compound I-20 is higher than that of benoxacor, thus the activity is higher than that of benoxacor. These findings demonstrate that phenyl isoxazole derivatives possess great potential for protective management in cornfields.

Efficacy and safety of laparoscopic bile duct exploration versus endoscopic sphincterotomy for concomitant gallstones and common bile duct stones: A meta-analysis of randomized controlled trials.

BACKGROUND: The purpose of this study was to compare the efficacy and safety of laparoscopic cholecystectomy (LC) plus laparoscopic common bile duct (CBD) stones exploration (LCBDE) with LC plus endoscopic sphincterotomy (EST) in the treatment of patients with gallstones and CBD stones. METHODS: The authors searched PubMed, Web of Science, and Embase to identify relevant studies. Risk ratios (RRs) were pooled to compare stone clear, retained stone, conversion to other procedures, and complications. Weighted mean differences (WMDs) were pooled to compare operative time, and length of hospital stay. A fixed-effects model or random-effects model was used to pool the estimates, according to the heterogeneity among the included studies. RESULTS: A total of 11 randomized controlled trials (RCTs) involving 1663 patients were included in this meta-analysis. The pooled estimate suggested that LC-LCBDE had comparable effects with LC-EST in terms of CBD stone clear rate (RR = 1.02, 95% CI: 0.95, 1.09; P = .583), retained stones rate (RR = 1.27, 95% CI: 0.51, 3.19; P = .607), and length of hospital stay (WMD = -0.96 days, 95% CI: -2.20, 0.28). In addition, LC-LCBDE was associated with significantly higher conversion rate (RR = 1.59, 95% CI: 1.08, 2.35; P = .019) and less operative time (WMD = -11.55 minutes, 95% CI: -16.68, -6.42; P < .001) than LC-EST. The incidence of complications was not significant difference between the 2 surgical approaches (RR = 1.07, 95% CI: 0.86, 1.34; P = .550). CONCLUSION: Based on the current evidence, both LC-LCBDE and LC-EST were highly effective in detecting and removing CBD stones and were equivalent in complications. However, our results might be biased by the limitations. Large-scale well-designed RCTs are needed to confirm our findings.

[Effects of preoperative carbohydrate loading on the changes in serum tumor necrosis factor receptors 1 and 2 and insulin resistance in patients of colon carcinoma].

OBJECTIVE: To investigate the effects of preoperative carbohydrate loading and new fasting protocol treatment on the postoperative changes in serum tumor necrosis factor receptor1 (sTNFR1), sTNFR2, and insulin resistance (IR) in patients of colon carcinoma. METHODS: 51 patients of colon carcinoma were randomly divided into 2 groups: carbohydrate-rich beverage group (n = 24), undergoing fasting 6 h before operation and water deprivation 2 h before operation, receiving carbohydrate-rich beverage 3 h before operation and fluid therapy with glucose post-operatively, and placebo group (n = 27) undergoing routine fasting and water deprivation pre-operatively. Peripheral blood samples were collected before, during, and 1, 4, and 7 d after operation. ELISA was used to detect the sTNFR1 and sTNFR2 of preoperative, 1, 4, 7day Insulin sensitivity index (S1) was calculated. RESULTS: The S(1) levels at different post-operational time points of the treatment group were not significantly different from those preoperatively (all P > 0.05), while the S(1) levels of the control group decreased significantly compared to those before operation (all P < 0.05). The sTNFR1 level of the treatment group increased postoperatively and did not return to the pre-operative level 7 d after operation(all P < 0.05). The sTNFR1 levels at different post-operative time points of the treatment group were all significantly higher than those of the control group (all P < 0.05). The sTNFR2 level of the treatment group decreased postoperatively and did not return to the pre-operative level 7d after operation (all P < 0.05). The sTNFR2 levels at different post-operative time points of the treatment group were all significantly lower than those of the control group (all P < 0.05). There was not significant differences in the sTNFR1 level in the control group before and after operation (all P > 0.05). The time to first flatus and days staying in hospital of the treatment group were (77 +/- 15) hours and (11 +/- 1.2) gays respectively, both significantly shorter than those of the control group [(86 +/- 13) hours and (15.1 +/- 3.8) days respectively, both P < 0.05]. CONCLUSION: Preoperative carbohydrate loading and new fasting protocol reduce the degree and course of IR, increase the sTNFR1 level, and decrease the sTNFR2 level and days of staying in hospital.