Selective Spectrophotometric and Spectrofluorometric Methods for the Determination of Amantadine Hydrochloride in Capsules and Plasma via Derivatization with 1,2-Naphthoquinone-4-sulphonate

New selective and sensitive spectrophotometric and spectrofluorometric methods have been developed and validated for the determination of amantadine hydrochloride (AMD) in capsules and plasma. The methods were based on the condensation of AMD with 1,2-naphthoquinone-4-sulphonate (NQS) in an alkaline medium to form an orange-colored product. The spectrophotometric method involved the measurement of the colored product at 460  nm. The spectrofluorometric method involved the reduction of the product with potassium borohydride, and the subsequent measurement of the formed fluorescent reduced AMD-NQS product at 382  nm after excitation at 293  nm. The variables that affected the reaction were carefully studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9972–0.9974) and low LOD (1.39 and 0.013 μg mL−1) were obtained in the ranges of 5–80 and 0.05–10  μg mL−1 for the spectrophotometric and spectrofluorometric methods, respectively. The precisions of the methods were satisfactory; RSD ≤2.04%. Both methods were successfully applied to the determination of AMD in capsules. As its higher sensitivity, the spectrofluorometric method was applied to the determination of AMD in plasma; the recovery was 96.3–101.2 ± 0.57–4.2%. The results obtained by the proposed methods were comparable with those obtained by the official metho

(Z)-Ethyl 2-cyano-2-{2-[5,6-dimethyl-4-(thio­phen-2-yl)-1H-pyrazolo­[3,4-b]pyridin-3-yl]hydrazinylidene}acetate

In the title compound, C17H16N6O2S, an intra­molecular N—H⋯O inter­action generates an S(6) ring. The pyridine ring makes a dihedral angle of 71.38 (11)° with the thio­phene ring. In the crystal, mol­ecules are linked by a pair of N—H⋯N hydrogen bonds, forming an inversion dimer. The dimers are stacked in columns along the b axis through weak inter­molecular C—H⋯N hydrogen bonds

Microwave-Assisted Solution-Phase Synthesis and DART-Mass Spectrometric Monitoring of a Combinatorial Library of Indolin-2,3-dione Schiff Bases with Potential Antimycobacterial Activity

A combinatorial library composed of eleven hydrazides A-K and eleven indolin-1,2-dione derivatives 1-11 has been designed to formally generate sublibraries of 22 mixtures, M1-M22 comprising of 121 Schiff bases, A-K(1-11). The designed library has been synthesized by the solution-phase method and microwave-assisted synthetic techniques. The formation of individual compounds of each mixture was confirmed by Direct Analysis in Real Time (DART) as ionization technique connected to an Ion Trap as a mass detector. The synthesized mixtures were evaluated for their antimycobacterial activity against four Mycobacterium strains; M. intercellulari, M. xenopi, M. cheleneoi and M. smegmatis. Variable antimycobacterial activity was revealed with the investigated mixtures and maximum activity was shown by M8, M10, M11, and M15 with MIC values of 1.5, 3.1, 6.2 and 0.09 μg/mL, respectively. Application of the indexed method of analysis on these active mixtures revealed that compounds D8, D10 and D11 may contribute to the activity of the tested mixtures

Tetrahydro-2H-1,3,5- thiadiazin-t-thione Derivatives of The optical Isomers of Phenylalanine, Synthesis, Comparative Stability Study and Antifungal Activity

In order to investigate the effect of the optical properties of the 5-substituent on the stability and the antihngal activity of tetrahydro-2H-1,3,5-thiadizine-2-thione (THTT) moiety, optical isomers and racemic mixture of phenylalanine were incorporated in the 5th position of THTT to afford derivatives 2a-g. Chemical and enzymatic stability of these derivatives were studied in vitro in aqueous buffer solution of pH 7.4, physiological pH, and 80% human plasma at 37°C using HPLC. The chemical and enzy\u27matic degradation rates of the tested compounds revealed that the optical properties of the 5-substituent of THTT moiety have no role on their stability at the investigated media. However, the chemical nature of the 3-substiuents has a significant effect on their chemical and enzymatic liability as 3-aralkyl derivatives, 2f and 2g , were the least stable compounds under the investigation conditions. Solid state stability of these derivatives was studied using Differential Scanning Calorimetry (DSC). In spite of the distinguished DSC curves of the racemic cornpounds from that of the corresponding single optical isomers no constant pattern of their thermal stability was observed. The antifbngal activity of 2a-g, was investigated in vitro against Cnndida albicans, C. parasilosis and C. stellatoidea using tube dilution method. No role for the optical properties of the tested compounds on their antifungal activity was observed. The utmost antihngal activity revealed by compound 2g which has 3-phenethyl substituent. Moreover, 2g has the highest lipophilicity and the most susceptible compound for both chemical and enzymatic degradations

Effect of selenium-containing compounds on hepatic chemoprotective enzymes in mice.

Selenite and organoselenium compounds have been examined at supranutritional levels for their ability to influence the activity and mRNA levels of chemoprotective enzymes in the livers of selenium-sufficient mice and the changes compared to those elicited by oltipraz. Compounds investigated included novel selenocysteine prodrugs that have previously been evaluated for their ability to reduce the tumorigenicity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in mice. Following seven daily doses (i.g.), all compounds except 2-methylselenazolidine-4(R)-carboxylic acid (MSCA) increased thioredoxin reductase activity (43-92%) but only for 2-oxoselenazolidine-4(R)-carboxylic acid (OSCA) was there an accompanying increase in mRNA. No compound enhanced glutathione peroxidase activity, although sodium selenite significantly elevated the mRNA of this enzyme. Oltipraz was an efficacious inducer of both thioredoxin reductase and glutathione peroxidase mRNAs. Sodium selenite, selenazolidine-4(R)-carboxylic acid (SCA), and OSCA elevated NAD(P)H-quinone oxidoreductase mRNA but only for OSCA was the elevation in mRNA accompanied by an increase in enzyme activity. L-Selenocystine significantly increased this activity without increasing mRNA levels. Sodium selenite, L-selenocystine, L-selenomethionine, and Se-methyl-L-selenocysteine all enhanced glutathione S-transferase activity. The increased activity with sodium selenite was accompanied by increases in mRNAs of Gst alpha, Gst mu and Gst pi classes, while for L-selenocystine and Se-methyl-L-selenocysteine, only an elevation in the mRNA for the Gst alpha class was observed. Gst alpha and Gst mu class mRNAs were elevated by OSCA without a significant elevation in enzyme activity. SCA and MSCA both elevated a Gst pi mRNA and MSCA elevated Gst mu in addition. By comparison, oltipraz only significantly elevated the mRNA of Gst mu, adding to the conclusion that across the entire study, no selenium compound appears to be acting purely through the antioxidant response typified by oltipraz. Despite their chemical similarity, the three cysteine prodrugs, SCA, MSCA, and OSCA, each produced its own unique pattern of effects on protective enzymes and none was identical to the pattern elicited by sodium selenite, L-selenocystine, L-selenomethionine, and Se-methyl-L-selenocysteine. The study also shows that after 7 days of administration, there was only occasional concordance between elevations in mRNA and enzyme activity for any selenium compound and for any protective enzyme, there was no response in common for all selenium compounds