Synthesis and biological evaluation of a class of quinolone triazoles as potential antimicrobial agents and their interactions with calf thymus DNA

A novel series of quinolone triazoles were synthesized and characterized by IR, NMR, MS and HRMS spectra. All the newly prepared compounds were screened for their antimicrobial activities against seven bacteria and four fungi. Bioactive assay manifested that most of new compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains including multi-drug resistant MRSA in comparison with reference drugs Norfloxacin, Chloromycin and Fluconazole. The preliminary interactive investigations of compound 6b with calf thymus DNA by fluorescence and UV–vis spectroscopic methods revealed that compound 6b could effectively intercalate DNA to form compound 6b–DNA complex which might block DNA replication and thus exert its antimicrobial activities.     

Systematic replacement of amides by 1,4-disubstituted[1,2,3]triazoles in Leu-enkephalin and the impact on the delta opioid receptor activity

Using Cu(I)-catalyzed azide–alkyne cycloaddition in a mixed classical organic phase and solid phase peptide synthesis approach, we synthesized four analogs of Leu-enkephalin to systematically replace amides by 1,4-disubstituted[1,2,3]triazoles. The peptidomimetics obtained were characterized by competitive binding, contractility assays and ERK1/2 phosphorylation. The present study reveals that the analog bearing a triazole between Phe and Leu retains some potency, more than all the others, suggesting that the hydrogen bond acceptor capacity of the last amide of Leu-enkephalin is essential for the biological activity of the peptide.     

Molecular dynamics simulation of complex Histones Deacetylase (HDAC) Class II Homo Sapiens with suberoylanilide hydroxamic acid (SAHA) and its derivatives as inhibitors of cervical cancer

Cervical cancer is second most common cancer in woman worldwide. Cervical cancer caused by human papillomavirus (HPV) oncogene. Inhibition of histone deacetylase (HDAC) activity has been known as a potential strategy for cancer therapy. SAHA is an HDAC inhibitor that has been used in cancer therapy but still has side effects. SAHA modification proposed to minimize side effects. Triazole attachment on the chain of SAHA has been known to enhance the inhibition ability of SAHA and less toxic. In this study, it will be carried out with molecular dynamic simulations of SAHA modifications consisting ligand 1a, 2a and, 2c to interact with six HDAC in hydrated conditions. To all six HDAC Class II, performed docking with SAHA and a modified inhibitor. The docking results were then carried out molecular dynamics simulations to determine the inhibitor affinities in hydrated conditions. The molecular dynamic simulations results show better affinities of ligand 2c with HDAC 4, 6, and 7 than SAHA itself, and good affinity was also shown by ligand 2a and 1c on HDAC 5 and 9. The results of this study can be a reference to obtain better inhibitors.     

桔梗新病害——匍柄霉叶斑病的病原生物学特性及药剂敏感性分析

桔梗匍柄霉叶斑病是近年来发现的新病害,病原菌为桔梗匍柄霉Stemphylium platycodontis。为了更好地了解病害的发生规律,本研究对该病原菌的生物学特性及药剂敏感性进行了分析。结果表明：25℃为该病原菌的最适生长温度和产孢温度;菌丝生长最适pH值为4,而最适合产孢的pH值为8;24h黑暗处理,对病原菌的菌丝生长和产孢都最有利;PCA培养基对菌丝生长最有利,而桔梗汁液培养基对病原菌产孢最有利;可溶性淀粉对菌丝生长最有利,而蔗糖最利于病原菌产孢;乙酰铵对病原菌生长及产孢都最有利;26.8μg/mL氟硅唑对桔梗匍柄霉的抑制效果最好,毒力持效性最强。     

Relationship between Late Soybean Diseases Complex and Rain in Determining Grain Yield Responses to Fungicide Applications

Wide distribution of soybean monoculture associated with no tillage has contributed to enhance damages caused by late diseases complex (LDC) in Argentina. LDC is a complex of diseases where Septoria glycines and Cercospora kikuchii are regarded as the major problem. Even though the use of foliar fungicides has increased, there is no rational and economic guide for their use. This is the main reason why the response to foliar fungicide applications is unpredictable. One of the main factors that contribute to the development of LDC is rainfall. The objective of this study was to evaluate the impact of rainfall during several growing seasons and different soybean growth stages on LDC severity and yield. We carried out 18 field experiments during three growing seasons (2004–2006) at several locations in the Argentine Pampas Region, to examine the relationship between rain and yield response to single fungicide applications (quinone outside inhibitors and demethylation inhibitors) at growing stages R3 and R5. The strongest associations (R² = 0.81–0.84; P < 0.001) were observed between accumulated rainfall from R3 to R5 and yield response to fungicides applied in R3 or R5. Our results suggest that a minimum of 65–90 mm rainfall during R3–R5 is required to justify fungicide application, with high probability that the use of fungicide will increase soybean yield as a consequence of disease control. These findings could lead to a simple model, useful as decision support system for use in planning and scheduling spray applications for LDC management in soybean crops.     

Syntheses of 1,2,3-triazolyl salicylamides with inhibitory activity on lipopolysaccharide-induced nitric oxide production

A 28-membered 1,2,3-triazolyl salicylamide library was synthesized via a Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition and evaluated for their abilities to inhibit NO production in LPS-activated RAW264.7 macrophage cells. Among 28 analogues, 29g showed a significant inhibitory activity (IC₅₀ = 12.8 μM). The inhibitory effects of 29g on LPS-mediated NO production in macrophage cells appeared to be associated with the suppression of iNOS expression.     

Differential reactivity of alpha and beta 2'-deoxyribonucleosides towards protonation and metalation

The reactivity of artificial 2'-deoxyribonucleosides, designed as nucleoside surrogates in metal-mediated base pairs, towards protonation and metalation has been shown to be dependent on the choice of the anomer. The alpha nucleosides comprising the aglycones imidazole, 1,2,4-triazole, benzimidazole and imidazo[4,5-b]pyridine are more basic than the respective beta nucleosides as was shown by a combined experimental and theoretical approach. The DeltapK(a) values observed experimentally are in the range of 0.19+/-0.03 to 0.41+/-0.07 (with the error representing three times the standard deviation of the mean value). An independent confirmation of this differential reactivity was obtained from density functional theory (DFT) calculations using 1,2,4-triazole nucleoside as an example. The result of these calculations is in good agreement with the experimental data (DeltapK(a)=0.16 vs. 0.21+/-0.07). The stability of the respective metal ion complexes of the anomeric 1,2,4-triazole nucleosides follows the same trend as that of the respective protonated nucleosides: Those of the alpha nucleoside are more stable than those of the beta nucleoside (Deltalogbeta(2)=0.6+/-0.2 for the 2:1 complex with Ag(+); Deltalogbeta(1)=0.51+/-0.07 for the 1:1 complex with Hg(2+)). These slightly different reactivities will be useful for fine-tuning the metal-ion binding behavior of oligonucleotides containing metal-mediated base pairs.     

Combined application of Pseudomonas fluorescens strain LRB3W1 with a low dosage of benomyl for control of cabbage yellows caused by Fusarium oxysporum f. sp. conglutinans

An antagonistic bacterium, Pseudomonas fluorescens strain LRB3W1, inhibited the fungal growth of Fusarium oxysporum f. sp. conglutinans in vitro and suppressed cabbage yellows caused by F. oxysporum f. sp. conglutinans. Under glasshouse conditions, the bacterium survived at ca. 10⁶-10⁷ CFU g^-1 in the cabbage rhizosphere for 4 weeks after the initial application. The chemical fungicide, benomyl, did not suppress the disease severity at low concentration (1 or 10 µg mL^-1). However, the disease severity was decreased by the combined application of a low dosage of benomyl with strain LRB3W1. Combined application of a low dosage of benomyl with strain LRB3W1 was more effective than treatment with the bacterium alone. The survival of strain LRB3W1 was not influenced by the presence of benomyl. This combined use of the biocontrol agent, strain LRB3W1, and a fungicide, benomyl, should be an attractive approach for suppressing cabbage yellows in sustainable agriculture because of the reduced chemical dosages needed for disease management.     

Synthesis of substituted septanosyl-1,2,3-triazoles

A carbohydrate-based oxepine, derived from 2-deoxy-d-arabino-hexopyranose, was used to prepare a family of septanosyl-1,2,3-triazoles in four steps. DMDO mediated epoxidation of the oxepine followed by trapping of the intermediate 1,2-anhydroseptanose by sodium azide gave the β-substituted glycosyl azide. The septanosyl azide was then reacted with a number of alkynes under thermal Huisgen or copper(I) mediated reaction conditions. Hydrogenolysis of benzyl protecting groups gave substituted septanosyl-1,2,3-triazoles. The new septanose-based structures were then evaluated as potential glycosidase inhibitors.     

Activity of fungicide mixtures against Botrytis cinerea isolates resistant to benzimidazoles,strobilurins and dicarboximides

Botrytis cinerea, the causal agent of grey mould in a broad range of crops, is considered a high‐risk plant pathogen for fungicide resistance development. The use of fungicide mixtures, particularly combinations with synergistic activity, can be a useful tactic to counteract resistance build‐up in pathogen populations. The present study aimed to investigate the effects of different ratios of two‐way mixtures of carbendazim, iprodione, kresoxim‐methyl, tebuconazole and penconazole on four B. cinerea isolates that were sensitive or resistant to benzimidazoles, dicarboximides and strobilurins. The isolates that were resistant to benzimidazoles and strobilurins had E198A and G143A mutations in β‐tubulin and cytochrome b genes, respectively. The mixtures had different effects on each of the isolates in vitro but, in 13 combinations, the synergistic effect was observed against all or three isolates. In greenhouse experiments, 11 fungicide combinations used in decreased (EC₇₅) concentrations showed the maximum control efficiency. The two follow‐up greenhouse experiments using six selected combinations revealed they were highly effective against additional isolates with various fungicide resistance profiles. The identified mixtures‐ratios have potential for use in grey mould management programs in the greenhouse.