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The catechol derivative RC-12 (WR 27653) (

As an alternate for the conventional glass-based pH sensor which is associated with problems like fragile nature, alkaline error, and potential drift, the development of a new redox-sensitive pH probe-modified electrode that could show potential, current-drift and surface-fouling free voltammetric pH sensing is a demanding research interest, recently. Herein, we report a substituted carbazole-quinone (Car-HQ) based new redox-active pH-sensitive probe that contains benzyl and bromo-substituents, immobilized multiwalled carbon nanotube modified glassy carbon (GCE/MWCNT@Car-HQ) and screen-printed three-in-one (SPE/MWCNT@Car-HQ) electrodes for selective, surface-fouling free pH sensor application. This new system showed a well-defined surface-confined redox peak at an apparent standard electrode potential, Eo′ = − 0.160 V versus Ag/AgCl with surface-excess value, Γ = 47 n mol cm−2 in pH 7 phosphate buffer solution. When tested with various electroactive chemicals and biochemicals such as cysteine, hydrazine, NADH, uric acid, and ascorbic acid, MWCNT@Car-HQ showed an unaltered redox-peak potential and current values without mediated oxidation/reduction behavior unlike the conventional hydroquinone, anthraquinone and other redox mediators based voltammetry sensors with serious electrocatalytic effects and in turn potential and current drifts. A strong π–π interaction, nitrogen-atom assisted surface orientation and C–C bond formation on the graphitic structure of MWCNT are the plausible reasons for stable and selective voltammetric pH sensing application of MWCNT@Car-HQ system. Using a programed/in-built three-in-one screen printed compatible potentiostat system, voltammetric pH sensing of 3 μL sample of urine, saliva, and orange juice samples with pH values comparable to that of milliliter volume-based pH-glass electrode measurements has been demonstrated.

Ozonide OZ439 is a synthetic peroxide antimalarial drug candidate designed to provide a single-dose oral cure in humans. OZ439 has successfully completed Phase I clinical trials, where it was shown to be safe at doses up to 1,600 mg and is currently undergoing Phase IIa trials in malaria patients. Herein, we describe the discovery of OZ439 and the exceptional antimalarial and pharmacokinetic properties that led to its selection as a clinical drug development candidate. In vitro, OZ439 is fast-acting against all asexual erythrocytic Plasmodium falciparum stages with IC 50 values comparable to those for the clinically used artemisinin derivatives. Unlike all other synthetic peroxides and semisynthetic artemisinin derivatives, OZ439 completely cures Plasmodium berghei -infected mice with a single oral dose of 20 mg/kg and exhibits prophylactic activity superior to that of the benchmark chemoprophylactic agent, mefloquine. Compared with other peroxide-containing antimalarial agents, such as the artemisinin derivatives and the first-generation ozonide OZ277, OZ439 exhibits a substantial increase in the pharmacokinetic half-life and blood concentration versus time profile in three preclinical species. The outstanding efficacy and prolonged blood concentrations of OZ439 are the result of a design strategy that stabilizes the intrinsically unstable pharmacophoric peroxide bond, thereby reducing clearance yet maintaining the necessary Fe(II)-reactivity to elicit parasite death.

Creatine is widely used as a dietary supplement for body builders to enhance athletic performance. As the monohydrate, its low solubility in water and high dose lead to water retention and gastrointestinal discomfort. Hence, alternative creatine derivatives with enhanced water solubility and potential therapeutic advantages have been synthesized. As a zwitterionic compound, creatine can form salts at the N-methyl guanidinium or carboxylic acid functional groups. In this study, we determined the aqueous solubilities and partition coefficients of six N-methyl guanidinium salts of creatine compared to those of creatine monohydrate; two of these were new salts, namely, creatine mesylate and creatine hydrogen maleate. The aqueous solubilities of the salts were significantly more than that of creatine monohydrate with the hydrochloride and mesylate being 38 and 30 times more soluble, respectively. The partition coefficients of the creatine salts were very low indicating their relatively high polarity. Permeabilities of creatine pyruvate, citrate, and hydrochloride in Caco-2 monolayers were compared to that of creatine monohydrate. Aside from the creatine citrate salt form that had reduced permeability, there were no significant differences in permeability characteristics in Caco-2 monolayers. Typical of an amphoteric compound, creatine is least soluble in the pH region near the isoelectric point.

The structure and stereochemistry of the cyclohexane substituents of analogues of arterolane (OZ277) had little effect on potency against Plasmodium falciparum in vitro. Weak base functional groups were not required for high antimalarial potency, but they were essential for high antimalarial efficacy in P. berghei-infected mice. Five new ozonides with antimalarial efficacy and ADME profiles superior or equal to that of arterolane were identified.

Reaction of N-aryl-β-amino alcohols with p-toluenesulphonyl chloride under phase transfer catalytic condition gave the corresponding N-aryl aziridines in good yields, whereas N-alkyl-β-amino alcohol [for e.g., L-ephedrine] gave the corresponding N-tosyl derivative as the major product, along with the expected N-alkyl aziridines in lower yield.

Dispiro 1,2,4-trioxanes and 1,2,4,5-tetraoxanes had superior efficacy against Fasciola hepatica than the corresponding ozonides (1,2,4-trioxolanes). For highest efficacy, spiroadamantane and carboxymethyl substructures were required. Three compounds completely cured F. hepatica-infected mice at single oral doses of 50 mg/kg and two were partially curative at single doses of 25 mg/kg.

In the title compound, 8-(2-bromo-4-methylphenyl)-4-methyl-2,7,7a,8,8a,9- hexahydropyrano[2′,3′:1,2]naphth[6,7]aziridin-2-one, C21H18BrNO2, the tetrahydrobenzene ring adopts a flattened boat conformation. The aziridine plane forms dihedral angles of 80.4 (1) and 59.1 (2)° with the tetrahydrobenzene ring plane and the N-phenyl substituent ring plane, respectively. The crystal structure is stabilized by weak C-H⋯O intermolecular hydrogen bonds and π-π stacking interactions of the coumarin ring.

Reaction of N-aryl-β-amino alcohols with p-toluenesulphonyl chloride under phase transfer catalytic condition gave the corresponding N-aryl aziridines in good yields, whereas N-alkyl-β-amino alcohol [for e.g., L-ephedrine] gave the corresponding N-tosyl derivative as the major product, along with the expected N-alkyl aziridines in lower yield.

In the title molecule, C 14 H 13 IO 3 , the coumarin ring system is planar and the fused cyclohexane ring adopts a half-chair conformation. The planes of the coumarin and cyclohexane rings form a dihedral angle of 8.5 (1)°. In the crystal, the hydroxyl group and the carbonyl O atom are involved in an O-H…O intermolecular hydrogen bond. The molecules are stacked at a perpendicular distance of 3.588 (8) A along the a axis.

We previously identified structurally diverse small molecule (non-peptidic) inhibitors (SMNPIs) of the botulinum neurotoxin serotype A (BoNT/A) light chain (LC). Of these, several (including antimalarial drugs) contained a 4-amino-7-chloroquinoline (ACQ) substructure and a separate positive ionizable amine component. The same antimalarials have also been found to interfere with BoNT/A translocation into neurons, via pH elevation of the toxin-mediated endosome. Thus, this structural class of small molecules may serve as dual-function BoNT/A inhibitors. In this study, we used a refined pharmacophore for BoNT/A LC inhibition to identify four new, potent inhibitors of this structural class (IC(50)'s ranged from 3.2 to 17 mu M). Molecular docking indicated that the binding modes for the new SMNPIs are consistent with those of other inhibitors that we have identified, further supporting our structure-based pharmacophore. Finally, structural motifs of the new SMNPIs, as well as two structure-based derivatives, were examined for activity, providing valuable information about pharmacophore component contributions to inhibition.

In the title compound, 8-(2-bromo-4-methylphenyl)-4-methyl-2,7,7a,8,8a,9- hexahydropyrano[2′,3′:1,2]naphth[6,7]aziridin-2-one, C21H18BrNO2, the tetrahydrobenzene ring adopts a flattened boat conformation. The aziridine plane forms dihedral angles of 80.4 (1) and 59.1 (2)° with the tetrahydrobenzene ring plane and the N-phenyl substituent ring plane, respectively. The crystal structure is stabilized by weak C-H⋯O intermolecular hydrogen bonds and π-π stacking interactions of the coumarin ring.

In the title compound, C 14 H 14 N 2 O 3 , the nitro group is twisted from coplanarity with the benzene ring by 3.8(3)°. The benzene ring is perpendicular to the phenyl ring. The molecules are packed around the threefold axis to form an infinite channel containing disordered solvent molecules. C-H...O, O-H...O and N-H...O intermolecular hydrogen bonds stabilize the crystal structure.

The coumarin rings in the title molecules, C 14 H 12 O 2 and C 14 H 12 O 3 , are planar. In the epoxide derivative, the tetrahydrobenzene ring adopts a boat conformation and the oxirane plane is nearly perpendicular to the coumarin moiety.

Single electron reduction of the 1,2,4-trioxane heterocycle of artemisinin (1) forms primary and secondary carbon-centered radicals. The complex structure of 1 does not lend itself to a satisfactory dissection of the electronic and steric effects that influence the formation and subsequent reaction of these carbon-centered free radicals. To help demarcate these effects, we characterized the reactions of achiral dispiro-1,2,4-trioxolane 4 and dispiro-1,2,4-trioxanes 5-7 with ferrous bromide and 4-oxo-TEMPO. Our results suggest a small preference for attack of Fe(II) on the nonketal peroxide oxygen atom of 1. For 4, but not for 5 and 6, there was a strong preference for attack of Fe(II) on the less hindered peroxide bond oxygen atom. The steric hindrance afforded by a spiroadamantane in a five-membered trioxolane is evidently much greater than that for a corresponding six-membered trioxane. Unlike 1, 5-7 fragment by entropically favored beta-scission pathways forming relatively stable alpha-oxa carbon-centered radicals. These data suggest that formation of either primary or secondary carbon-centered radicals is a necessary but insufficient criterion for antimalarial activity of 1 and synthetic peroxides.

The quinolone ring system in C 10 H 10 N 2 O.H 2 o is essentially planar. The hydrogen-bonding scheme involves O-H...O, N-H...O, N-H...N and C-H...O interactions.

Systematic studies were performed on the photo-Fries and the Fries reaction of aliphatic, aliphatic unsaturated, aromatic and aromatic unsaturated esters of 5,8-dihydro-1-naphthol. The Fries reaction of 5,8-dihydro-1-naphthyl acetate in various solvents is also reported.

In the title compound, C17H21NO3S, the S atom is in a distorted tetrahedral geometry and the N atom exhibits sp2 character. The antiperiplanar conformation is observed for the N and hydroxyl-O atoms and the torsion angle around the N—C linkage is −136.3 (2)°. The mol­ecules are linked by O—H⋯O intermolecular hydrogen bonds to form an infinite one-dimensional chains along the c axis.

The coumarin and phenyl rings of the title molecule, C 22 H 20 O 4 S, are individually planar. The tetrahydro-benzene ring adopts a half-chair conformation. The crystal structure is stabilized by C-H...O hydrogen bonds involving the carbonyl O atoms.

In the title molecule (alternative name: 8-hydroxy-4-methyl-9-phenylthio-7,8,9,10-tetrahydro-2H-benzo-[f]chromen-2-one; C 20 H 18 O 3 S), the tetrahydrobenzene ring is in a half-chair conformation. The planes of the coumarin and thiophenyl rings form a dihedral angle of 126.31(5)°. The crystal structure is stabilized by OH...O hydrogen bonds involving carbonyl and hydroxy O atoms.