approach for mosquito control. Further understanding of the molecular mechanisms involved would help identify additional novel targets for vector control using ATSB.

BackgroundDiscovery of potent inhibitors of urease (jack bean) enzyme is the first step in the development of drugs against diseases caused by ureolytic enzyme.ResultsThirty-two derivatives of barbituric acid as zwitterionic adducts of diethyl ammonium salts were synthesized. All synthesized compounds (4a–z and 5a–s) were screened for their in vitro inhibition potential against urease enzyme (jack bean urease). The compounds 4i (IC50 = 17.6 ± 0.23 µM) and 5l (IC50 = 17.2 ± 0.44 µM) were found to be the most active members of the series, and showed several fold more urease inhibition activity than the standard compound thiourea (IC50 = 21.2 ± 1.3 µM). Whereas, compounds 4a–b, 4d–e, 4g–h, 4j–4r, 4x, 4z, 5b, 5e, 5k, 5n–5q having IC50 values in the range of 22.7 ± 0.20 µM–43.8 ± 0.33 µM, were also found as potent urease inhibitors. Furthermore, Molecular Dynamics simulation and molecular docking studies were carried out to analyze the binding mode of barbituric acid derivatives using MOE. During MD simulation enol form is found to be more stable over its keto form due to their coordination with catalytic Nickel ion of Urease. Additionally, structural–activity relationship using automated docking method was applied where the compounds with high biological activity are deeply buried within the binding pocket of urease. As multiple hydrophilic crucial interactions with Ala169, KCX219, Asp362 and Ala366 stabilize the compound within the binding site, thus contributing greater activity.ConclusionsThis research study is useful for the discovery of economically, efficient viable new drug against infectious diseases.Graphical abstract:STD. Thiourea (IC50 = 21.2 ± 1.3 µM)Electronic supplementary materialThe online version of this article (doi:10.1186/s13065-015-0140-1) contains supplementary material, which is available to authorized users.

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In the continuation of our work to synthesize enzyme inhibitors, we synthesized 3,4,5-tri hydroxybenzohydrazones (1-19) from 3,4,5-trihydroxybenzohydrazide, which were obtained from methyl 3,4,5-trihydroxybenzoate by refluxing with hydrazine hydrate. All the synthesized compounds were characterized by different spectroscopic methods. The synthesized compounds were evaluated for urease inhibition and showed excellent results, close to the standards thiourea. The kinetic studies on the five most active compounds 6, 10, 14, 16 and 18 were carried out to determine their mode of inhibition and dissociation constant K i . The compounds 6 and 16 were found to be competitive inhibitors with K i values 19.1 and 10.53 lM, respectively, while the compounds 10, 14 and 18 were found to be mixed-type of inhibitors with K i values in the range of 18.4-21.7 lM. ª 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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RNA-interference (RNAi) is a standard technique for functional genomics in adult mosquitoes. However, RNAi in immature, aquatic mosquito stages has been challenging. Several studies have shown successful larval RNAi, usually in combination with a carrier molecule. Except for one study in malaria mosquito, Anopheles gambiae, none of the previous studies has explored RNAi in mosquito pupae. Even in the study that used RNAi in pupae, double stranded RNA (dsRNA) was introduced by microinjection. Here, we describe a successful method by soaking pupae in water containing dsRNA without any carrier or osmotic challenge. The knockdown persisted into adulthood. We expect that this simple procedure will be useful in the functional analysis of genes that highly express in pupae or newly emerged adults.

Urotropine (1) is a synthetic heterocyclic antibacterial agent.

We report herein the biological activities of several imidazolium aurate(I) salts. The cytotoxicity on three cell‐lines (i. e. Hela, H460 and 3T3), enzyme inhibition on a panel of five enzymes (i. e. prolyl endopeptidase, butyrylcholinesterase, tyrosinase, dipeptidyl peptidase and carbonic anhydrase), iron chelation and in vitro Leishmanicidal assay for promastigotes are described. A comparison with other data found in the literature using similar standards to our control experiment is also discussed. Finally, all these data lead us to establish some structure‐activity correlations and to determine the potential importance of the gold moiety in these salts.