Effects of Different Weak Small Organic Acids on Clofazimine Solubility in Aqueous Media.

Background/objectives: Clofazimine (CFZ) is a Biopharmaceutics Classification System (BCS) II drug introduced in the US market in 1986 for the treatment of leprosy. However, CFZ was later withdrawn from the market due to its extremely low aqueous solubility and low absorption. In the literature, the intrinsic solubility of CFZ has been estimated to be <0.

Blue-light-driven photoactivity of L-cysteine-modified graphene quantum dots and their antibacterial effects.

The widespread abuse of traditional antibiotics has led to a global rise in antibiotic-resistant bacteria, which give in return unprecedented health risks. Therefore, there is a large and urgent need for the development of new, smart antibacterial agents able to efficiently kill or inhibit bacterial growth. In this study, we investigated the antibacterial activity of S, N-doped Graphene Quantum Dots (GQDs) as a light-triggered antibacterial agent.

Clofazimine p Determination by Potentiometry and Spectrophotometry: Reverse Cosolvent Dependence as an Indicator of the Presence of Dimers in Aqueous Solutions.

The weakly basic antibiotic and anti-inflammatory drug, clofazimine (CFZ), was first described in 1957. It has been used therapeutically, most notably in the treatment of leprosy. However, the compound is extremely insoluble in aqueous media, and, indeed, there is poor consensus about what its intrinsic solubility is since the reported values range from 0.

Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pH Domains with a Gibbs Phase Rule "Soft" Constraints.

The solubility of a model basic drug, nortriptyline (Nor), was investigated as a function of pH in phosphate and/or a chloride-containing aqueous suspension using experimental practices recommended in the previously published "white paper" (Avdeef et al., 2016). The pH-Ramp Shake-Flask (pH-RSF) method, introduced in our earlier work (Marković et al.

A novel method of molecular imprinting applied to the template cholesterol.

A novel method is successfully tested for non-covalent imprinting. Conditions are used which practically exclude the formation of prepolymerization complexes. The template is cholesterol, and no so-called functional monomer is used.

Second generation of diazachrysenes: Protection of Ebola virus infected mice and mechanism of action.

Ebola virus (EBOV) causes a deadly hemorrhagic fever in humans and non-human primates. There is currently no FDA-approved vaccine or medication to counter this disease. Here, we report on the design, synthesis and anti-viral activities of two classes of compounds which show high potency against EBOV in both in vitro cell culture assays and in vivo mouse models Ebola viral disease.

New Steroidal 4-Aminoquinolines Antagonize Botulinum Neurotoxin Serotype A in Mouse Embryonic Stem Cell Derived Motor Neurons in Postintoxication Model.

The synthesis and inhibitory potencies against botulinum neurotoxin serotype A light chain (BoNT/A LC) using in vitro HPLC based enzymatic assay for various steroidal, benzothiophene, thiophene, and adamantane 4-aminoquinoline derivatives are described. In addition, the compounds were evaluated for the activity against BoNT/A holotoxin in mouse embryonic stem cell derived motor neurons. Steroidal derivative 16 showed remarkable protection (up to 89% of uncleaved SNAP-25) even when administered 30 min postintoxication.

Human serum albumin binding of certain antimalarials.

Interactions between eight in-house synthesized aminoquinolines, along with well-known chloroquine, and human serum albumin (HSA) have been studied by fluorescence spectroscopy. The synthesized aminoquinolines, despite being structurally diverse, were found to be very potent antimalarials. Fluorescence measurements indicate that three compounds having additional thiophene or benzothiophene substructure bind more strongly to HSA than other studied compounds.

Synthesis and characterisation of bismacrocyclic DO3A-amide derivatives - an approach towards metal-responsive PARACEST agents.

Three new bismacrocyclic Ln(3+) chelates consisting of triamide derivatives of cyclen with glycine, methyl and tert-butyl substituents (, respectively) linked to an acyclic EGTA-derived calcium chelator were synthesised as potential MRI contrast agents (EGTA - ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid). Eu(3+) and Yb(3+) complexes of were investigated as chemical exchange saturation transfer (CEST) agents. Moderate to minor CEST effects were observed for , and complexes in the absence of Ca(2+), with negligible changes upon addition of this metal ion.

Reinvestigating Old Pharmacophores: Are 4-Aminoquinolines and Tetraoxanes Potential Two-Stage Antimalarials?

The syntheses and antiplasmodial activities of various substituted aminoquinolines coupled to an adamantane carrier are described. The compounds exhibited pronounced in vitro and in vivo activity against Plasmodium berghei in the Thompson test. Tethering a fluorine atom to the aminoquinoline C(3) position afforded fluoroaminoquinolines that act as intrahepatocytic parasite inhibitors, with compound 25 having an IC50 = 0.

Binding capacity of molecularly imprinted polymers and their nonimprinted analogs.

Molecularly imprinted polymers bind their target compounds at binding sites. The binding sites are typically based on some type of functional group, such as carboxyl group. The total amount of such functional groups and their distribution into available and unavailable groups is not well known.

Comparison of the single channel and multichannel (multivariate) concepts of selectivity in analytical chemistry.

Different measures of selectivity are in use for single channel and multichannel linear analytical measurements, respectively. It is important to understand that these two measures express related but still distinctly different features of the respective measurements. These relationships are clarified by introducing new arguments.

Anthelmintic activity in vivo of epiisopiloturine against juvenile and adult worms of Schistosoma mansoni.

Schistosomiasis is a serious disease currently estimated to affect more that 207 million people worldwide. Due to the intensive use of praziquantel, there is increasing concern about the development of drug-resistant strains. Therefore, it is necessary to search for and investigate new potential schistosomicidal compounds.

Investigation into novel thiophene- and furan-based 4-amino-7-chloroquinolines afforded antimalarials that cure mice.

We herein report the design and synthesis of a novel series of thiophene- and furan-based aminoquinoline derivatives which were found to be potent antimalarials and inhibitors of β-hematin polymerization. Tested compounds were 3-71 times more potent in vitro than CQ against chloroquine-resistant (CQR) W2 strain with benzonitrile 30 being as active as mefloquine (MFQ), and almost all synthesized aminoquinolines (22/27) were more potent than MFQ against multidrug-resistant (MDR) strain C235. In vivo experiments revealed that compound 28 showed clearance with recrudescence at 40 mg/kg/day, while 5/5 mice survived in Thompson test at 160 mg/kg/day.

Selectivity in analytical chemistry: two interpretations for univariate methods.

Selectivity is extremely important in analytical chemistry but its definition is elusive despite continued efforts by professional organizations and individual scientists. This paper shows that the existing selectivity concepts for univariate analytical methods broadly fall in two classes: selectivity concepts based on measurement error and concepts based on response surfaces (the response surface being the 3D plot of the univariate signal as a function of analyte and interferent concentration, respectively). The strengths and weaknesses of the different definitions are analyzed and contradictions between them unveiled.

Synthesis and characterization of pH-sensitive, biotinylated MRI contrast agents and their conjugates with avidin.

Responsive or smart contrast agents (SCAs) provide new opportunities in magnetic resonance imaging (MRI) to examine a number of physiological and pathological events. However, their application in vivo remains challenging. Therefore, much research is focused on the optimization of their properties, to enable their use in additional imaging modalities, pre-targeted delivery, or to increase the local concentration of the agent.

Correlation between structure, retention, property, and activity of biologically relevant 1,7-bis(aminoalkyl)diazachrysene derivatives.

The physicochemical properties, retention parameters (R(M)(0)), partition coefficients (logP(OW)), and pK(a) values for a series of thirteen 1,7-bis(aminoalkyl) diazachrysene (1,7-DAAC) derivatives were determined in order to reveal the characteristics responsible for their biological behavior. The investigated compounds inhibit three unrelated pathogens (the Botulinum neurotoxin serotype A light chain (BoNT/A LC), Plasmodium falciparum malaria, and Ebola filovirus) via three different mechanisms of action. To determine the most influential factors governing the retention and activities of the investigated diazachrysenes, R(M)(0), logP(OW), and biological activity values were correlated with 2D and 3D molecular descriptors, using a partial least squares regression.