Design, synthesis and biological evaluation of indole-2-carboxylic acid derivatives as novel HIV-1 integrase strand transfer inhibitors.

Integrase plays an important role in the life cycle of HIV-1, and integrase strand transfer inhibitors (INSTIs) can effectively impair the viral replication. However, drug resistance mutations have been confirmed to decrease the efficacy of INSTI during the antiviral therapy. Herein, indole-2-carboxylic acid (1) was found to inhibit the strand transfer of integrase, and the indole nucleus of compound 1 was observed to chelate with two Mg2+ ions within the active site of integrase. Through optimization of compound 1, a series of indole-2-carboxylic acid derivatives were designed and synthesized, and compound 17a was proved to markedly inhibit the effect of integrase, with IC50 value of 3.11 µM. Binding mode analysis of 17a demonstrated that the introduced C6 halogenated benzene ring could effectively bind with the viral DNA (dC20) through π-π stacking interaction. These results indicated that indole-2-carboxylic acid is a promising scaffold for the development of integrase inhibitors.

Design, synthesis, and in vitro protective effect evaluation of α-carboline derivatives against H2O2-induced cardiomyocyte injury.

As one of the most important features of myocardial ischemia reperfusion (MI/R) injury, the overproduction of reactive oxygen species (ROS) overwhelms the intrinsic antioxidant and impairs the function of mitochondria and, finally, leads to cardiomyocyte death. To improve the damage of cardiomyocyte caused by oxidative stress, a series of α-carboline derivatives were designed and synthesized in this study. The biological studies revealed that most of the α-carbolines exhibited obvious protective activities against H2O2-induced cardiomyocyte injury. Among them, compound 14b significantly increased the cell viability in H2O2-induced oxidative stress in H9c2 cardiomyoblasts with a concentration-dependent manner, which was more potent than polydatin. Pretreatment of 14b obviously inhibited H2O2-induced lactate dehydrogenase (LDH) leakage, enhanced the capacity of endogenous antioxidant defenses, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and reduced the formation of the toxic product of lipid peroxidation (malondialdehyde, MDA). In addition, 14b effectively reduced the overproduction of ROS and restored the mitochondrial membrane potential ΔΨm, better than that of polydatin. Flow cytometry analysis demonstrated that 14b markedly reduced both necrosis and apoptosis in H9c2 cells after the exposure to H2O2. Further Western blot analysis revealed that 14b obviously decreased the ratio of Bax/Bcl-2 and reduced the expression of cytochrome c. Overall, these results revealed the potential of α-carboline 14b as a promising cardioprotective agent against H2O2-induced oxidative injury.

[Life history traits of an Echinochloa crus-galli var. crus-galli population with extreme adaptations to rice planting systems]. / 特异性适应稻作系统的稗草种群生活史特性.

Long-term herbicide application may facilitate the adaptive evolution of weed populations. With Echinochloa crus-galli var. crus-galli population A from a rice field used for the experiment of effectiveness of herbicide in Nanling County, Anhui Province, we conducted common garden experi-ments with seeds of population A and three control populations collected from normal rice fields. Compared with the three control populations, population A had significantly lower seed production for individual plant, but higher 1000-seed weight. Population A had faster in seedling growth, higher in number of reproductive tillers, shorter life span, lower in height and biomass of individual plant, as well as lower in sensitivity to herbicide penoxsulam. Individuals from population A survived from 2× label dose (60 g·hm-2) of penoxsulam treatment at the three- to four-leaf stage showed significantly reduction in plant height, biomass, and mature seed production (1066 seeds per plant), but no difference in heading period, number of reproductive tillers, number of seeds per raceme and 1000-seed weight. The short lifespan, heavy seeds, dwarf architecture, more reproductive tillers and penoxsulam resistance made E. crus-galli var. crus-galli population A extremely adapting to rice planting systems, which should be prevented to spread to normal rice fields.

Typhaneoside prevents acute myeloid leukemia (AML) through suppressing proliferation and inducing ferroptosis associated with autophagy.

Leukemia remains a fatal disease for most patients and effective therapeutic strategies are urgently required. Typhaneoside (TYP) is a major flavonoid in the extract of Pollen Typhae, showing significant biological and pharmacological effects. In the present study, we explored the effects of TYP on acute myeloid leukemia (AML) progression. The results indicated that TYP markedly reduced the cell viability of AML cells and arrested the cell cycle at the G2/M phase by regulating the expression of associated proteins. In addition, TYP significantly induced apoptosis in AML cells by promoting the activation of Caspase-3. Intracellular and mitochondrial reactive oxygen species (ROS) accumulation were highly detected in AML cells after treatment with TYP. Moreover, TYP clearly induced ferroptosis in AML cells, and this process was iron-dependent and attendant with mitochondrial dysfunction. We also found that TYP significantly triggered autophagy in AML cells by promoting the activation of AMP-activated protein kinase (AMPK) signaling, contributing to ferritin degradation, ROS accumulation and ferroptotic cell death ultimately. In conclusion, the findings above provided solid evidences that TYP could be a promising therapeutic agent to prevent AML progression by inducing apoptosis, ROS production, autophagy and ferroptosis.

Increasing seriousness of plant invasions in croplands of eastern china in relation to changing farming practices: a case study.

Arable areas are commonly susceptible to alien plant invasion because they experience dramatic environmental influences and intense anthropogenic activity. However, the limited reports on relevant factors in plant invasion of croplands have addressed single or a few invasive species and environmental factors. To elucidate key factors affecting plant invasions in croplands, we analyzed the relationship between 11 effective factors and changes in composition of alien plants, using field surveys of crop fields in Anhui Province conducted during 1987-1990 (historical dataset) and 2005-2010 (recent dataset), when rapid urbanization was occurring in China. We found that in the past few decades, the dominance and richness of alien plant populations approximately doubled, despite differences among the 4 regions of Anhui Province. Among the 38 alien invasive plant species observed in the sites, the dominance values of 11 species increased significantly, while the dominance of 4 species decreased significantly. The quantity of chemical fertilizer and herbicide applied, population density, agricultural machinery use, traffic frequency, and annual mean temperature were significantly related to increased richness and annual dominance values of alien plant species. Our findings suggest that the increase in alien plant invasions during the past few decades is primarily a result of increased application of chemical fertilizer and herbicides.