A hybrid pharmacophore approach is used to design and synthesize two novel series of 2′-hydroxychalcone-triazole hybrid molecules 6a-j and 8a-j. These compounds were fully characterized by spectral and elemental analyses. They were evaluated in vitro and in vivo for anti-inflammatory activity. Most of compounds were selective inhibitors for COX-2. Among them, compounds 6d, 6f, 6i, 8c, 8e and 8h demonstrated highly potent dual inhibition of COX-2 (IC50 = 0.037–0.041 µM) and 15-LOX (IC50 = 1.41–1.80 µM). Compounds 6i, 8c and 8h showed 116%, 113% and 109% of the in vivo anti-inflammatory activity of celecoxib. Therefore, compounds 6d, 6f, 6i, 8c, 8e and 8h-j are potent dual inhibitors of COX-2 and 15-LOX. Docking study over COX-2 and 15- LOX active sites ensures the binding affinity and selectivity. These compounds are promising candidates for further development as anti-inflammatory drugs.

A hybrid pharmacophore approach is used to design and synthesize two novel series of 2′-hydroxychalcone-triazole hybrid molecules 6a-j and 8a-j. These compounds were fully characterized by spectral and elemental analyses. They were evaluated in vitro and in vivo for anti-inflammatory activity. Most of compounds were selective inhibitors for COX-2. Among them, compounds 6d, 6f, 6i, 8c, 8e and 8h demonstrated highly potent dual inhibition of COX-2 (IC50 = 0.037–0.041 µM) and 15-LOX (IC50 = 1.41–1.80 µM). Compounds 6i, 8c and 8h showed 116%, 113% and 109% of the in vivo anti-inflammatory activity of celecoxib. Therefore, compounds 6d, 6f, 6i, 8c, 8e and 8h-j are potent dual inhibitors of COX-2 and 15-LOX. Docking study over COX-2 and 15- LOX active sites ensures the binding affinity and selectivity. These compounds are promising candidates for further development as anti-inflammatory drugs.

A hybrid pharmacophore approach is used to design and synthesize two novel series of 2′-hydroxychalcone-triazole hybrid molecules 6a-j and 8a-j. These compounds were fully characterized by spectral and elemental analyses. They were evaluated in vitro and in vivo for anti-inflammatory activity. Most of compounds were selective inhibitors for COX-2. Among them, compounds 6d, 6f, 6i, 8c, 8e and 8h demonstrated highly potent dual inhibition of COX-2 (IC50 = 0.037–0.041 µM) and 15-LOX (IC50 = 1.41–1.80 µM). Compounds 6i, 8c and 8h showed 116%, 113% and 109% of the in vivo anti-inflammatory activity of celecoxib. Therefore, compounds 6d, 6f, 6i, 8c, 8e and 8h-j are potent dual inhibitors of COX-2 and 15-LOX. Docking study over COX-2 and 15- LOX active sites ensures the binding affinity and selectivity. These compounds are promising candidates for further development as anti-inflammatory drugs.

The applicability of ninhydrin, a widely used derivatizing reagent, for determination of teicoplanin (TEIC) in its pure form, pharmaceutical vials, and in human plasma was investigated. The presented spectrofluorimetric method was based on a condensation reaction between ninhydrin and the primary amine group existing in TEIC (in the presence of phenylacetaldehyde) to produce a highly fluorescent product detected at 460 nm (λex,390 nm). Calibration plots were constructed in the concentration range 60–600 ng mL–1 with a good correlation coefficient of 0.9998 and a low detection limit of 10.84 ng mL–1. The method was subjected to a bioanalytical validation study according to US‐FDA recommendations. The proposed method was applied for analysis of TEIC in commercial vials with high recovery result 101.88 ± 1.11%. In addition, the method was utilized efficiently for detection of TEIC in human plasma using salting‐out assisted liquid–liquid extraction technique (SALLE) with a recovery range from 96.71 ± 1.08% to 97.71 ± 0.86%. SALLE is an effective approach used for extraction of TEIC from human plasma without interferences using ammonium sulphate. The proposed method is highly recommended to monitor TEIC in clinical laboratory samples and therapeutic drug monitoring systems.

The applicability of ninhydrin, a widely used derivatizing reagent, for determination of teicoplanin (TEIC) in its pure form, pharmaceutical vials, and in human plasma was investigated. The presented spectrofluorimetric method was based on a condensation reaction between ninhydrin and the primary amine group existing in TEIC (in the presence of phenylacetaldehyde) to produce a highly fluorescent product detected at 460 nm (λex,390 nm). Calibration plots were constructed in the concentration range 60–600 ng mL–1 with a good correlation coefficient of 0.9998 and a low detection limit of 10.84 ng mL–1. The method was subjected to a bioanalytical validation study according to US‐FDA recommendations. The proposed method was applied for analysis of TEIC in commercial vials with high recovery result 101.88 ± 1.11%. In addition, the method was utilized efficiently for detection of TEIC in human plasma using salting‐out assisted liquid–liquid extraction technique (SALLE) with a recovery range from 96.71 ± 1.08% to 97.71 ± 0.86%. SALLE is an effective approach used for extraction of TEIC from human plasma without interferences using ammonium sulphate. The proposed method is highly recommended to monitor TEIC in clinical laboratory samples and therapeutic drug monitoring systems.

A selective and highly sensitive high performance liquid chromatography (HPLC) with fluorescence derivatization method was developed for determination of ethinyl estradiol (EE); one of endocrine-disrupting compounds (EDCs). The fluorescence derivatization procedure was based on Sonogashira coupling reaction using 4-(4, 5-diphenyl-1H-imidazole-2-yl) iodobenzene (DIB-I), a fluorescence labeling reagent, to derivatize EE in presence of copper and palladium ions. The formed fluorescent product was separated on Cosmosil 5C18 MS-II by an isocratic elution with a mobile phase composed of acetonitrile: 5.0 mM Tris-HNO3 buffer, pH 7.4 (60:40, v/v %). The detection wavelengths were set at 310 and 400 nm as excitation and emission wavelengths, respectively. Various parameters affecting derivatization reaction were optimized. Further, the proposed method was validated and a good linearity with low detection limit (S/N=3) 7.4 ng L−1 was obtained in water sample after a simple solid-phase disk extraction (C18 SPE disk) method. The proposed method was successfully applied for detection of EE in river water samples in order to monitor EE concentration and to distinguish its effect on the ecosystem and human health.

A potential microtubule destabilizing series of new thirty-five Pyrrol-2-one, Pyridazin-3(2H)-one and Pyridazin-3(2H)-one/oxime derivatives has been synthesized and tested for their antiproliferative activity against a panel of 60 human cancer cell lines. Compounds IVc, IVg and IVf showed a broad spectrum of growth inhibitory activity against cancer cell lines representing renal, cancer of lung, colon, central nervous system, ovary, and kidney. Among them, compound IVg was found to have broad spectrum anti-tumor activity against the tested nine tumor subpanels with selectivity ratios ranging between 0.21 and 3.77 at the GI50 level. In vitro assaying revealed tubulin polymerization inhibition by all active compounds IVc, IVg and IVf. The results of the docking study revealed nice fitting of compounds IVc, IVf, and IVg into CA-4 binding site in tubulin. The three compounds exhibited high binding affinities (Gb = -12.49 to -12.99 kcal/mol) toward tubulin compared to CA-4 (-8.87 kcal/mol). Investigation of the binding modes of the three compounds IVc, IVf, and IVg revealed that they interacted mainly hydrophobically with tubulin and similar binding orientations to that of CA-4. These observations suggest that tubulin is a possible target for these compounds.

New quinoline / chalcone hybrids containing 1,2,4-triazole moiety have been designed, synthesized and their structures elucidated and confirmed by various spectroscopic techniques. The designed compounds showed moderate to good activity on different NCI 60 cell lines in a single-dose assay with a growth inhibition rate ranging from 50% to 94%. Compounds 7b, 7d, 9b, and 9d were the most active compounds in most cancer cell lines with a growth inhibition percent between 77% and 94%. Newly synthesized hybrids were evaluated for their anti-proliferative activity against a panel of four human cancer cell lines. Compounds 7a, 7b, 9a, 9b, and 9d showed promising antiproliferative activities. These compounds were further tested for their inhibitory potency against EGFR and BRAFV600E kinases with erlotinib as a reference drug. The molecular docking study of compounds 7a, 7b, 9a, 9b, and 9d revealed nice fitting into the active site of EGFR and BRAFV600E kinases. Compounds 7b, 9b, and 9d displayed the highest binding affinities and similar binding pattern to those of erlotinib.

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