Beneficial effects of abscisic acid and melatonin in overcoming drought stress in cotton (Gossypium hirsutum L.).

Pot experiments were performed to study the effects of abscisic acid (ABA) and melatonin (MT) on cotton drought tolerance and to explore their combined effects. ABA or MT spraying promoted water status and antioxidant capacity of drought-stressed leaves, which was conducive to scavenge ROS, finally increasing lint yield. However, the mitigation mechanisms of ABA and MT on drought were not identical, which were mainly manifested as: (1) ABA increased the relative water content (RWC) of drought-stressed leaves via, reducing water loss, but MT increased it via, promoting water uptake efficiency; (2) for enzymatic antioxidant system, ABA and MT might modulate different kinds of superoxide dismutase to catalyze the reduction of O2 - under drought; and (3) for ascorbic acid (AsA)-glutathione (GSH) cycle, MT increased the glutathione reductase activity in drought-stressed leaves, but ABA did not. ABA + MT spraying led to higher leaf RWC and total antioxidant capacity than single hormone under drought, leading to a lower H2 O2 level. For the enzymatic antioxidant system, single hormone treatment affected Cu/ZnSOD or MnSOD expression, but ABA + MT upregulated both genes in drought-stressed leaves. Hormones combined application also had higher CAT expression than single hormone. For AsA-GSH cycle, ABA + MT had higher dehydroascorbic acid reductase activity than single hormone, resulting in higher AsA content. Moreover, hormones combined application caused higher ascorbate peroxidase activity than single hormone, suggesting that their combination synergistically improved the ability of AsA to eliminate ROS. All these confirmed that ABA plus MT had synergistic effects on improving crop drought resistance.

Design and synthesis of 2-((1H-indol-3-yl)thio)-N-phenyl-acetamides as novel dual inhibitors of respiratory syncytial virus and influenza virus A.

Respiratory syncytial virus (RSV) and influenza A virus (IAV) are two of the most common viruses that cause substantial morbidity and mortality in infants, young children, elderly persons, and immunocompromised individuals worldwide. Currently, there are no licensed vaccines or selective antiviral drugs against RSV infections and most IAV strains become resistant to clinical anti-influenza drug. Here, we described the discovery of a series of 2-((1H-indol-3-yl)thio)-N-phenyl-acetamide as novel and potent RSV and IAV dual inhibitors. Thirty-five derivatives were designed, prepared, and evaluated for their anti-RSV and anti-IAV activities. Among the tested compounds, 14'c, 14'e, 14'f, 14'h, and 14'i exhibited excellent activity against both RSV and IAV, which showed low micromolar to sub-micromolar EC50 values. Further, compounds 14'c and 14'e were identified as the most promising dual inhibitors with lesser cytotoxicity than the clinical drug, ribavirin. These findings may contribute to the development of a lead compound for the treatment of RSV and/or IAV infections.

Synthesis and Biological Evaluation of Substituted Indole and Its Analogs as Influenza A Virus Inhibitors.

Influenza A virus (IAV), a highly pathogenic virus to human beings, is most susceptible to mutation and thus causes rapid, severe global pandemics resulting in millions of fatalities worldwide. Since resistance to the existing anti-influenza drugs is developing, innovative inhibitors with a different mode of action are urgently needed. The lead compound 6092B-E5 has proven to be an effective antiviral reagent in our previous work. Using the principles of substitution and bioisosterism of the indole ring, six series of novel anti-IAV target products were designed, synthesized and evaluated for their antiviral effect in this work. Compounds D1 , D3 , D9 , G1 , G3 , G12 and G23 were identified as promising anti-IAV candidates with excellent anti-IAV efficacy (IC50 values of 3.06-5.77 µm) and low cytotoxicity (CC50 values up to and beyond 100 µm). This work represents a successful application of the substitution and bioisosteric replacement strategy for the discovery of novel antiviral molecules that can be used for further structural optimization.