O3浓度升高对小麦根际土壤酶活性和有机酸含量的影响

近地层臭氧(O₃)浓度升高作为全球气候变化的重要因素之一,对土壤生态环境和农作物生长发育造成了很大影响.本研究采用开顶式气室(OTCs)法,探究臭氧浓度升高对小麦不同生育期(分蘖期、拔节期、孕穗期和成熟期)根际土壤酶活性(过氧化氢酶、多酚氧化酶、脱氢酶和转化酶)和有机酸含量(草酸、柠檬酸和苹果酸)的影响规律,并结合根际土壤理化性质、植株根系生长状况等分析其产生影响的原因.结果表明: O₃浓度升高不同程度地提高了小麦成熟期土壤过氧化氢酶、多酚氧化酶、脱氢酶和转化酶活性,其中过氧化氢酶和多酚氧化酶活性提高达显著水平;在抽穗期,脱氢酶和转化酶活性因臭氧浓度升高而显著提高,增幅最高可达76.7%.在成熟期,O₃浓度升高显著提高了根际土壤中柠檬酸和苹果酸含量;显著降低了根际土壤pH、电导率、总碳和总氮含量,增加了土壤氧化还原电位(Eh);显著降低了小麦根系生物量、总根长和根总表面积,而增加了根平均直径.     

不同CO2浓度下大豆叶片的光合生理生态特性

CO₂是光合作用的原料和底物,影响着光合作用的进程和光合产物的数量.利用Li-6400-40B同时测量大豆叶片在不同CO₂浓度(300、400、500和600 μmol·mol^-1)下的光合电子传递速率和光合作用对光的响应曲线,并用构建的光合作用对光响应机理模型拟合这些光响应曲线,获得大豆叶片一系列的光合参数、生理生态参数和捕光色素分子的物理参数.结果表明: 电子利用效率、最大电子传递速率和最大净光合速率随CO₂浓度的升高而增加;光补偿点和暗呼吸速率随CO₂浓度的升高而下降;光能利用效率和内禀(瞬时)水分利用效率随CO₂浓度的升高而增加,不同CO₂浓度下的最大光能利用效率和最大内禀(瞬时)水分利用效率之间存在显著差异,但不同CO₂浓度下的最大羧化效率的差异不显著.CO₂浓度的大小对光合作用中原初光反应存在一定程度的影响,即高CO₂浓度有利于减小捕光色素分子处于最低激发态的最小平均寿命,以提高光能传递的速度及增加大豆光合电子流的利用效率.     

Quinone skeleton as a new class of irreversible inhibitors against Staphylococcus aureus sortase A

Sortase A (SrtA) anchors surface proteins to the cell wall and aids biofilm formation during infection, which functions as a key virulence factor of important Gram-positive pathogens, such as Staphylococcus aureus. At present researchers need a way in which to validate whether or not SrtA is a druggable target alternative to the conventional antibiotic targets in the mechanism. In this study, we performed a high-throughput screening and identified a new class of potential inhibitors of S. aureus SrtA, which are derived from natural products and contain the quinone skeleton. Compound 283 functions as an irreversible inhibitor that covalently alkylates the active site Cys184 of SrtA. NMR analysis confirms the direct interaction of the small-molecule inhibitor towards SrtA protein. The anchoring of protein A (SpA) to the cell wall and the biofilm formation are significantly attenuated when the S. aureus Newman strain is cultured in the presence of inhibitor. Our study indicates that compound 283 could be a potential hit for the development of new anti-virulence agents against S. aureus infections by covalently targeting SrtA.     

Synthesis and biological evaluation of 1-amino isochromans from 2-bromoethyl benzaldehyde and amines in acid medium

We have developed a facile and efficient synthetic route to substituted isochromans for the first time by reacting 2-(2-bromoethyl)benzaldehyde with a variety of aryl, heteroaryl amines in AcOH. The reaction is catalyst/additive free and takes place at reflux conditions with short reaction time to furnish products in good to excellent yields. All the compounds have been characterized by spectral techniques such as IR, ¹H NMR and Mass etc. Synthesized compounds were evaluated for antimicrobial activity against specific bacterial like 1) Staphylococcus strains aureus 2) Bacillus subtilis 3) Escherichia coli 4) Pseudomonas aeruginosa. Compounds 3e, 3n, 3?m, 3?l, 3?k, 3j and 3b showed most potent in vitro activity against bacterial strains.     

Synthesis and biological evaluation of aminothiazoles against Histoplasma capsulatum and Cryptococcus neoformans

The design and synthesis of a library of forty novel 2-aminoazole analogues as well as their evaluation as antifungal compounds against Histoplasma capsulatum and Cryptococcus neoformans is described. These structures were derived from N-[5-(1-naphthalenylmethyl)-2-thiazolyl]cyclohexanecarboxamide (41F5), a fungistatic agent previously identified through phenotypic screening (Antimicrob Agents Chemother. 2013;57:4349). Modifications to improve potency and water-solubility of 41F5 focused primarily on the 5-naphthalenyl group, the thiazole core, and the methylene linker between these two structural elements. In general, compounds with lipophilic [5+6] bicyclic ring systems, such as the 7-benzothiophenyl- and 4-indanyl groups, at the 5-position were 2–3 times more active against both fungal species as compared to 41F5. Also, introduction of a carbonyl group at the methylene linker of 41F5 resulted in a 2–3-fold increase in potency. These highly active compounds also showed generally low toxicities against murine P388D1 macrophages resulting in selectivity indices ranging from 63 to >200. Compounds that were highly active against fluconazole-sensitive C. neoformans strains had almost identical activity against fluconazole-resistant variants of this fungus indicating that 14α-demethylase is not their molecular target. Highly active compounds also retained activity against H. capsulatum phagocytosed into P388D1 macrophages.     

In vitro and in vivo anti-inflammatory properties of imine resveratrol analogues

Resveratrol is a natural polyphenol found mainly on red grapes and in red wine, pointed as an important anti-inflammatory/immunomodulatory molecule. However, its bioavailability problems have limited its use encouraging the search for new alternatives agents. Thus, in this study, we synthetize 12 resveratrol analogues (6 imines, 1 thioimine and 5 hydrazones) and investigated its cytotoxicity, antioxidant activity and in vitro anti-inflammatory/immunomodulatory properties. The most promising compounds were also evaluated in vivo. The results showed that imines presented less cytotoxicity, were more effective than resveratrol on DPPH scavenger and exhibited an anti-inflammatory profile. Among them, the imines with a radical in the para position, on the ring B, not engaged in an intramolecular hydrogen-interaction, showed more prominent anti-inflammatory activity modulating, in vivo, the edema formation, the inflammatory infiltration and cytokine levels. An immunomodulatory activity also was observed in these molecules. Thus, our results suggest that imines with these characteristics presents potential to control inflammatory disorders.     

Resveratrol-maltol hybrids as multi-target-directed agents for Alzheimer’s disease

The 3-hydroxypyran-4-one moiety (maltol) was incorporated into the structure of resveratrol to achieve a series of resveratrol-maltol hybrids (8a–8k) as novel multi-target-directed ligands (MTDLs). In vitro biological evaluation of the MTDLs revealed these compounds to have a triple function, namely inhibition of self-induced Aβ_1–42 aggregation, antioxidation, and metal chelating activity. Among all the evaluated MTDLs, compounds 8i and 8j showed the most promise, demonstrating micromolar IC₅₀ values for Aβ_1–42 aggregation inhibition, more potent ABTS⁺ scavenging activity than Trolox, and good metal chelating activities.     

Design,synthesis, in vitro and in vivo evaluation,and structure-activity relationship (SAR) discussion of novel dipeptidyl boronic acid proteasome inhibitors as orally available anti-cancer agents for the treatment of multiple myeloma and mechanism studies

A series of novel dipeptidyl boronic acid inhibitors of 20S proteasome were designed and synthesized. Aliphatic groups at R¹ position were designed for the first time to fully understand the SAR (structure–activity relationship). Among the screened compounds, novel inhibitor 5c inhibited the CT-L (chymotrypsin-like) activity with IC₅₀ of 8.21?nM and the MM (multiple myeloma) cells RPMI8226, U266B and ARH77 proliferations with the IC₅₀ of 8.99, 6.75 and 9.10?nM, respectively, which showed similar in vitro activities compared with the compound MLN2238 (biologically active form of marketed MLN9708). To investigate the oral availability, compound 5c was esterified to its prodrug 6a with the enzymatic IC₅₀ of 6.74?nM and RPMI8226, U266B and ARH77 cell proliferations IC₅₀ of 2.59, 4.32 and 3.68?nM, respectively. Furthermore, prodrug 6a exhibited good pharmacokinetic properties with oral bioavailability of 24.9%, similar with MLN9708 (27.8%). Moreover, compound 6a showed good microsomal stabilities and displayed stronger in vivo anticancer efficacy than MLN9708 in the human ARH77 xenograft mouse model. Finally, cell cycle results showed that compound 6a had a significant inhibitory effect on CT-L and inhibited cell cycle progression at the G2M stage.