Is imidacloprid an effective alternative for controlling pyrethroid-resistant populations of Triatoma infestans (Hemiptera: Reduviidae) in the Gran Chaco ecoregion?

The prevention of Chagas disease is based primarily on the chemical control of Triatoma infestans (Klug) using pyrethroid insecticides. However, high resistance levels, correlated with control failures, have been detected in Argentina and Bolivia. A previous study at our laboratory found that imidacloprid could serve as an alternative to pyrethroid insecticides. We studied the delayed toxicity of imidacloprid and the influence of the blood feeding condition of the insect on the toxicity of this insecticide; we also studied the effectiveness of various commercial imidacloprid formulations against a pyrethroid-resistant T. infestans population from the Gran Chaco ecoregion. Variations in the toxic effects of imidacloprid were not observed up to 72 h after exposure and were not found to depend on the blood feeding condition of susceptible and resistant individuals. Of the three different studied formulations of imidacloprid on glass and filter paper, only the spot-on formulation was effective. This formulation was applied to pigeons at doses of 1, 5, 20 and 40 mg/bird. The nymphs that fed on pigeons treated with 20 mg or 40 mg of the formulation showed a higher mortality rate than the control group one day and seven days post-treatment (p < 0.01). A spot-on formulation of imidacloprid was effective against pyrethroid-resistant T. infestans populations at the laboratory level.

Development of a monoclonal antibody against deoxynivalenol for magnetic nanoparticle-based extraction and an enzyme-linked immunosorbent assay

Monoclonal antibody (mAb, NVRQS-DON) against deoxynivalenol (DON) was prepared. DON-Ag coated enzyme linked immunosorbent assay (ELISA) and DON-Ab coated ELISA were prepared by coating the DON-BSA and DON mAb. Quantitative DON calculation ranged from 50 to 4,000 ng/mL for DON-Ab coated ELISA and from 25 to 500 ng/mL for DON-Ag coated ELISA. 50% of inhibitory concentration values of DON, HT-2, 15-acetyl-DON, and nivalenol were 23.44, 22,545, 5,518 and 5,976 ng/mL based on the DON-Ab coated ELISA. Cross-reactivity levels of the mAb to HT-2, 15-acetyl-DON, and nivalenol were 0.1, 0.42, and 0.40%. The intra- and interassay precision coefficient variation (CV) were both <10%. In the mAb-coated ELISA, mean DON recovery rates in animal feed (0 to 1,000 microg/kg) ranged from 68.34 to 95.49% (CV; 4.10 to 13.38%). DON in a buffer solution (250, 500 and 1,000 ng/mL) was isolated using 300 microg of NVRQS-DON and 3 mg of magnetic nanoparticles (MNPs). The mean recovery rates of DON using this mAb-MNP system were 75.2, 96.9, and 88.1% in a buffer solution spiked with DON (250, 500, and 1,000 ng/mL). Conclusively we developed competitive ELISAs for detecting DON in animal feed and created a new tool for DON extraction using mAb-coupled MNPs.

Comparative QSAR modeling of COX-2 inhibitor 1,2-diarylimidazoles using E-state and physicochemical parameters.

Considering importance of developing selective COX-2 inhibitors, COX-2 binding affinity data of 4-(2-aryl-1-imidazolyl)-phenyl methyl sulfones and sulfonamides (n = 83) have been modeled using electrotopological state (E-state) index as electronic parameter, hydrophobic substituent constant (pi) and molar refractivity (MR) of aryl ring substituents as lipophilic and steric parameters, respectively. Additionally, suitable dummy parameters have been used for the development of multiple regression equations in a stepwise manner. The study suggests that lipophilicity of ortho, meta and para substituents of the aryl ring increases the binding affinity, while molar refractivity (MR) of ortho and meta substituents of the aryl ring decreases the binding affinity. Again, electron-withdrawing substituents at meta and para positions of the aryl ring increase the binding affinity. Additionally, a 4-fluoro substituent on the aryl ring, a trifluoromethyl substituent at R position and simultaneous presence of 3-chloro and 4-methyl groups on the aryl ring are conducive to the binding affinity. Also, an amino substituent is preferred over a methyl group at R2 position suggesting preference of the sulfonamide moiety over the methyl sulfone moiety for the COX-2 binding affinity. Furthermore, importance of E-state values of different atoms in the generated relations suggests the influence of electron density distribution over the 1,2-diarylimidazole nucleus for the binding affinity. For this data set, E-state parameters perform better as electronic parameters in comparison to Hammett sigma parameters. When lipophilic whole molecular descriptor (ClogP) is used, instead of hydrophobic substituent constant (pi), the former performs better than the latter.

Synthesis and some reactions of 4-[2-Alkyl-2-arylhydrazono]-2-phenyloxazol-5-o ne derivatives

A series of new 4-[2-alkyl-2-arylhydrazono]-2-phenyloxazol-5-ones derivatives 2a-d were synthesized by reaction of the oxazolones 1a, b with methyl and ethyl iodides. On the other hand, trial to alkylate 1a with methyl bromoacetate or phenacyl bromide afforded the triazine 3 and pyridinone 7, respectively. The reaction of 2a, b with ammonia or primary aromatic amines or hydrazines gave the acyclic amides 8a, b, 10a-d and hydrazides 12a-d, respectively. Cyclization of 8a, b and 10a, b gave imidazoles 9a, b, and 11a, b. While cyclization of 12a-d afforded triazines 13a, b and 14a, b, respectively

Exploring selectivity requirements for peripheral versus central benzodiazepine receptor binding affinity: QSAR modeling of 2-phenylimidazo[1,2-a]pyridine acetamides using topological and physicochemical descriptors.

Considering the potential of peripheral benzodiazepine receptor (PBR) ligands in therapeutic applications and clinical benefit in the management of a large spectrum of different indications, quantitative structure-activity relationship (QSAR) study has been attempted to explore the structural and physicochemical requirements for selectivity of 2-phenylimidazo[1,2-a]pyridineacetamides for binding with peripheral over central benzodiazepine receptors (CBRs). For PBR binding affinity, molar refractivity (MR) shows a parabolic relation with binding affinity suggesting that binding affinity increases with increase in volume of the compounds, until it reaches the critical value, after which the affinity decreases. The negative coefficients of S_aaN and S_ssNH indicate that binding affinity increases with decrease in E-state value of (N/) (aromatic nitrogen) and HN< (secondary amino group) fragments. The coefficient of 3XVC and JX term indicates the importance of shape and branching for binding affinity. For CBR binding affinity, lipophilicity of molecules is detrimental to the binding affinity, while presence of hydrogen at Y position is conducive to the activity. Selectivity pattern of these ligands for peripheral (cortex) over central receptors requires the presence and absence of methyl group at R2 and R3 positions respectively, and shows the importance of MR and shape parameter. Similarly, selectivity of these ligands for peripheral (ovary) over central receptors requires the presence and absence of methyl group at R2 and R3 positions respectively, presence of phenyl group at R1 and R2 positions and selectivity relation shows importance of MR, shape and branching.

Quantitative structure-activity relationship of 4,5-diphenyl-2-(substituted thio)-1H-imidazoles as the inhibitors of acyl CoA: cholesterol acyltransferase.

A quantitative structure-activity relationship (QSAR) analysis of 4,5-diphenyl-2-(substituted thio)-1H-imidazoles as the potential inhibitors of acyl CoA: cholesterol acyltransferase is presented with a view to reflect upon the parametric requirement of various substitutions. For this purpose the van der Waals volume, Vw which is the measure of molecular bulk/size of substituents present at R1- and R2-positions has emerged as the befitting correlative parameter. A number of correlations obtained amongst different subclasses of the title compounds have helped in ascertaining the relative importance of X-substituents and the role of Vw(R1) and Vw(R2). Finally, a significant correlation between the sum of van der Waals volume of R1- and R2-substituents, sigma Vw and biological activities of the entire series was also derived. From the resulting parabolic QSAR equation, an optimum molecular bulk of 1.846 x 10(2) A3 leading to the highest potent compound of the series, specially among those congeners which have X = -NH-, was predicted. This finding has, therefore, hinted at the existence of a cavity, capable of accommodating the maximum steric bulk, on to the receptor.

Antiparkinsonian activity and dopamine receptor binding studies of imidazolone derivatives.

Mannich bases and styryl derivatives of imidazolones were evaluated for their antiparkinsonian activity. Two compounds showed potent antiparkinsonian activity. These active compounds also showed binding with dopamine receptors in striatal membrane preparation of rat brain.