5324-47-0Relevant articles and documents
Discovery, Synthesis and Evaluation of a Ketol-Acid Reductoisomerase Inhibitor
Bayaraa, Tenuun,Kurz, Julia L.,Patel, Khushboo M.,Hussein, Waleed M.,Bilyj, Jessica K.,West, Nicholas P.,Schenk, Gerhard,McGeary, Ross P.,Guddat, Luke W.
, p. 8958 - 8968 (2020/07/04)
Ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway, is a potential drug target for bacterial infections including Mycobacterium tuberculosis. Here, we have screened the Medicines for Malaria Venture Pathogen Box against purified M. tuberculosis (Mt) KARI and identified two compounds that have Ki values below 200 nm. In Mt cell susceptibility assays one of these compounds exhibited an IC50 value of 0.8 μm. Co-crystallization of this compound, 3-((methylsulfonyl)methyl)-2H-benzo[b][1,4]oxazin-2-one (MMV553002), in complex with Staphylococcus aureus KARI, which has 56 % identity with Mt KARI, NADPH and Mg2+ yielded a structure to 1.72 ? resolution. However, only a hydrolyzed product of the inhibitor (i.e. 3-(methylsulfonyl)-2-oxopropanic acid, missing the 2-aminophenol attachment) is observed in the active site. Surprisingly, Mt cell susceptibility assays showed that the 2-aminophenol product is largely responsible for the anti-TB activity of the parent compound. Thus, 3-(methylsulfonyl)-2-oxopropanic acid was identified as a potent KARI inhibitor that could be further explored as a potential biocidal agent and we have shown 2-aminophenol, as an anti-TB drug lead, especially given it has low toxicity against human cells. The study highlights that careful analysis of broad screening assays is required to correctly interpret cell-based activity data.
Towards the Prediction of Global Solution State Properties for Hydrogen Bonded, Self-Associating Amphiphiles
White, Lisa J.,Tyuleva, Stilyana N.,Wilson, Ben,Shepherd, Helena J.,Ng, Kendrick K. L.,Holder, Simon J.,Clark, Ewan R.,Hiscock, Jennifer R.
supporting information, p. 7761 - 7773 (2018/05/08)
Through this extensive structure–property study we show that critical micelle concentration correlates with self-associative hydrogen bond complex formation constant, when combined with outputs from low level, widely accessible, computational models. Herein, we bring together a series of 39 structurally related molecules related by stepwise variation of a hydrogen bond donor–acceptor amphiphilic salt. The self-associative and corresponding global properties for this family of compounds have been studied in the gas, solid and solution states. Within the solution state, we have shown the type of self-associated structure present to be solvent dependent. In DMSO, this class of compound show a preference for hydrogen bonded dimer formation, however moving into aqueous solutions the same compounds are found to form larger self-associated aggregates. This observation has allowed us the unique opportunity to investigate and begin to predict self-association events at both the molecular and extended aggregate level.
Secondary-Structure-Driven Self-Assembly of Reactive Polypept(o)ides: Controlling Size, Shape, and Function of Core Cross-Linked Nanostructures
Klinker, Kristina,Sch?fer, Olga,Huesmann, David,Bauer, Tobias,Capel?a, Leon,Braun, Lydia,Stergiou, Natascha,Schinnerer, Meike,Dirisala, Anjaneyulu,Miyata, Kanjiro,Osada, Kensuke,Cabral, Horacio,Kataoka, Kazunori,Barz, Matthias
supporting information, p. 9608 - 9613 (2017/08/01)
Achieving precise control over the morphology and function of polymeric nanostructures during self-assembly remains a challenge in materials as well as biomedical science, especially when independent control over particle properties is desired. Herein, we report on nanostructures derived from amphiphilic block copolypept(o)ides by secondary-structure-directed self-assembly, presenting a strategy to adjust core polarity and function separately from particle preparation in a bioreversible manner. The peptide-inherent process of secondary-structure formation allows for the synthesis of spherical and worm-like core-cross-linked architectures from the same block copolymer, introducing a simple yet powerful approach to versatile peptide-based core–shell nanostructures.
ABSORPTION OF DIETHYL DISULFIDE BY SODIUM HYPOCHLORITE SOLUTIONS.
Oparina,Perchuzov,Novgorodskaya,Bolmosov,Stepanov
, p. 1184 - 1188 (2007/10/02)
Results are presented of a study of the kinetics of the absorption of diethyl disulfide by aqueous solutions of sodium hypochlorite and the reaction of their liquid interaction. The absorption process was studied in the a column with a continuous bubbling layer subdivided by sieve plates. It is found that aqueous solutions of sodium hypochlorite efficiently scrub diethyl disulfide from the air. In a column with a continuous bubbling layer subdivided by sieve plates, the absorption process is limited by the mass transfer in the gas phase. The reaction whereby diethyl disulfide is oxidized in the liquid phase by a solution of sodium hypochlorite was studied and the probable process mechanism suggested.
Studies on Sulphochlorination of Paraffins. VIII. Studies on the Hydrolysis of Individual Alkane Sulphochlorides by Sodium Hydroxide
Hampel, M.,Just, G.,Krebes, W.,Pritzkow, W.
, p. 987 - 990 (2007/10/02)
The hydrolysis of individual C1-C5 alkane sulphochlorides by sodium hydroxide in dioxane/water (1:1) was kinetically studied at 25 deg C by means of stopped-flow technique, measuring the change of electric conductivity.The rate constants were influenced by steric hindrance, but in all cases were higher than the rate constant for alkaline hydrolysis of benzene sulphochloride, which cannot react according to the elimination-addition (sulphene) mechanism.The reaction enthalpy of the alkaline hydrolysis of four individual alkane sulphochlorides was determined by a simple calorimetric apparatus; the average value amounts to ΔRH = -239 kJ mol-1.
