Binary and ternary complexes of sulphamethoxazole

Summary The complex formation equilibria involved in the binary and ternary systemsM(II)-sulpha andM(II)-phen-sulpha were investigated by potentiometric titrations at 25°C and a ionic strength of 0.1N NaNO₃ (M = Cu, Ni, Co, Zn;sulpha = sulphamethoxazole;phen = phenanthroline). The stability constants of the binary and ternary complexes follow the order ofIrving andWilliam. The formation of the ternary complex is discussed in terms of the binary species. The mode of chelation was ascertained by conductivity measurements.

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Binäre und ternäre Komplexe von Sulphamethoxazol

Zusammenfassung Die an den binären und ternären SystemenM(II)-sulpha undM(II)-phen-sulpha (M = Cu, Ni, Co, Zn;sulpha = Sulphamethoxazol;phen = Phenanthrolin) beteiligten Komplexbildungsgleichgewichte wurden bei 25°C und einer Ionenstärke von 0.1N NaNO₃ mittels potentiometrischer Titration untersucht. Die Stabilitätskonstanten der binären und ternären Komplexe gehorchen der Reihenfolge vonIrving undWilliam. Die Bildung der ternären Komplexe wird auf der Basis der binären Spezies diskutiert. Die Art der Chelatbildung wurde durch Leitfähigkeitsmessungen ermittelt.

     

A novel inhibitor, 2-cyano-3-(1-phenyl-3-(thiophen-2-yl)-pyrazol-4-yl)acrylamide linked to sulphamethoxazole,blocks anti-apoptotic proteins via molecular docking and strongly induced apoptosis of HCT116 cell line by different molecular tools

A new series of cyanoacrylamides incorporating sulphamethoxazol were prepared and confirmed by different spectral tools. Anticancer screening of the new compounds was done against three different types of carcinoma cell lines involving (A₅₄₉, HCT₁₁₆, and MDA) using MTT assay. Compound 7 among all tested derivatives achieved the best cytotoxic effect against all tested carcinoma cell lines. HCT₁₁₆ revealed the best sensitivity and cytotoxic activity toward compound 7 relative to 5-FU. The target compound offered less toxic effect when tested on normal melanocytes (HFB4). Simulation modeling studies revealed strong binding affinity toward the following domains (1dls, 2c6o, and 2wgj) and moderate binding modes toward (3eyl, 4kmp, 2w3l, and 5lab) domains with different binding energy scores. Gene expression profile outlined that caspase-3, BAX, and P53 genes were strongly upregulated relative to their control, while BCL2, MMP1, and CDK2 were effectively down regulated assuming the activation of the apoptotic pathway. Flow cytometry technique revealed that compound 7 stimulated cell cycle arrests at the G2/M phase. Other extensive molecular diagnostic tools were utilized in this report as ELISA, DPA, SEM, and TEM assays which confirmed that our target novel compound 7 was a very promising and interesting chemotherapeutic agent with less toxic effect. Also, authors herein suggested that additional sulphamethoxazole linked to 3-(1-phenyl-3-(thiophen-2-yl)-1H-pyrazol-4-yl)acrylonitrile in compound 7 was responsible for its promising cytotoxic activity against colorectal carcinoma cell line.     

Fluorimetric Determination of Sulphaguanidine and Sulphamethoxazole by Host-Guest Complexation in β-Cyclodextrin and Partial Least Squares Calibration

The host-guest inclusion complexes of sulphamethoxazole (SMTX) and sulphaguanidine (SGN) with β-cyclodextrin, in aqueous solutions, have been investigated. A 1:1 stoichiometry of the complexes was established, the association constants were calculated by different methods, and the influence of several chemical variables on the complexation processes were established. According to the results obtained, a spectrofluorimetric method for the determination of these sulphonamides has been proposed. The individual and binary mixtures of both sulphonamides have been determined in human urine samples, at representative therapeutic ranges, by application of a first-order multivariate calibration partial least squares (PLS-1) model. The calibration set was designed with 9 samples, containing different concentrations of the two sulphonamides, and 8 blank urine samples, with the aim of modelling the variability of the background. The concentration ranges for the sulphonamides were up to 0.5 μg mL⁻¹ for SMTX and 1.0 μg mL⁻¹ for SGN. Figures of merit as selectivity, analytical sensitivity and limit of detection (LOD) were also calculated. The proposed procedure was validated by comparing the obtained results with a HPLC method, with satisfactory results for the assayed method.