Design, synthesis and biological evaluation of novel β-substituted indol-3-yl ethylamido melatoninergic analogues

A series of new melatonin analogues have been synthesized. Interestingly, two of the new compounds, 11c and 11e, which did not show any appreciable affinity for the melatonin receptor, were found to be potent inhibitors of lipid peroxidation in rat liver microsomes. Analogue 11c, in particular, is a better antioxidant than melatonin

Development and validation of a reversed-phase ion-pair liquid chromatography method for the determination of magnesium ascorbyl phosphate and melatonin in cosmetic creams

A reversed-phase ion-pair high-performance liquid chromatographic method was developed and validated for the determination of magnesium ascorbyl phosphate and melatonin in cosmetic creams. The determination was performed on a BDS C 18 analytical column (250 × 4.6 mm i.d., 5 μm particle size); the mobile phase consisted of 0.020 M tetrabutylammonium hydroxide and 0.025 M potassium dihydrogen phosphate (pH 6.8) mixed with acetonitrile in a ratio (77:23, v/v) and pumped at a flow rate 1.00 ml min-1. The UV detector was operated at 260 nm. The retention times of the magnesium ascorbyl phosphate, melatonin and chlorthalidone that was used as internal standard, were 6.55, 9.18 and 11.07 min, respectively. Calibration graphs are linear (r better than 0.9990, n = 6), in concentration range 1.00-10.00 μg ml-1 for magnesium ascorbyl phosphate and 0.63-6.25 μg ml-1 for melatonin. The intra- and inter-day R.S.D. values were less than 6.0%, while the relative percentage error Er was less than 3.5% (n = 5). The quantitation limits were 0.69 and 0.47 μg ml-1, for magnesium ascorbyl phosphate and melatonin, respectively. The method was applied to the analysis of a cosmetic cream and proved to be suitable for rapid and reliable quality control. © 2006 Elsevier B.V. All rights reserved

Development and validation of a reversed-phase ion-pair liquid chromatography method for the determination of magnesium ascorbyl phosphate and melatonin in cosmetic creams

A reversed-phase ion-pair high-performance liquid chromatographic method was developed and validated for the determination of magnesium ascorbyl phosphate and melatonin in cosmetic creams. The determination was performed on a BDS C 18 analytical column (250 × 4.6 mm i.d., 5 μm particle size); the mobile phase consisted of 0.020 M tetrabutylammonium hydroxide and 0.025 M potassium dihydrogen phosphate (pH 6.8) mixed with acetonitrile in a ratio (77:23, v/v) and pumped at a flow rate 1.00 ml min-1. The UV detector was operated at 260 nm. The retention times of the magnesium ascorbyl phosphate, melatonin and chlorthalidone that was used as internal standard, were 6.55, 9.18 and 11.07 min, respectively. Calibration graphs are linear (r better than 0.9990, n = 6), in concentration range 1.00-10.00 μg ml-1 for magnesium ascorbyl phosphate and 0.63-6.25 μg ml-1 for melatonin. The intra- and inter-day R.S.D. values were less than 6.0%, while the relative percentage error Er was less than 3.5% (n = 5). The quantitation limits were 0.69 and 0.47 μg ml-1, for magnesium ascorbyl phosphate and melatonin, respectively. The method was applied to the analysis of a cosmetic cream and proved to be suitable for rapid and reliable quality control. © 2006 Elsevier B.V. All rights reserved

Antitumor activity of imidazothioxanthones in murine and human tumor models in vitro and in vivo

Background: A new series of imidazothioxanthones has recently been synthesized as potential anticancer agents with the aim of overcoming drug resistance. The route of synthesis and DNA-binding properties of the compounds were reported previously. This paper describes the general structure-activity relationships for the class of imidazothioxanthones in panels of human and murine tumor cell lines in vitro, and the in vivo activity against human and murine solid tumors of the most potent compound, N-[3-(Dimethylamino)propylo]-11-oxo-11H-benzothiopyrano (3;2’: 2, 3)pyrido(1,2-a) imidazo-2carboxamide (10a). In addition, the interaction between compound 10a and DNA is also considered in terms of molecular mechanics methods and flexible docking techniques. Materials and Methods: The cytotoxicity of compounds 10a, 11-oxo-N-(2(pyrrolidino)ethylo)-11H-benzothiopyrano (3;2’:2,3)pyrido[1,2a] imidazo-2-carboxamide, 11-oxo-N-(2-(piperidino)ethylo)-11H-benzothiopyrano [3;2’:2,3]pyrido(1,2-a) imidazo-2-carboxamide and N-(2-(morpholino)ethylo)-11-oxo-11H-benzothiopyrano [3;2’: 2, 3]pyrido(1,2-a)imidazo-2-carboxamide (10c-10e) was assessed in human tumor cell lines and xenografts using the sulforhodamine B assay, MTT assay and the clonogenic assay. The human ovarian xenograft, PXN/109TC, two human breast carcinomas. MT-1 and MCF-7, and the murine colon adenocarcinoma, MAC 15A were used for the in vivo testing of compound 10a. In addition, the interaction between compound 10a and DNA is also considered in terms of molecular mechanics methods and flexible docking techniques. Results: Two compounds, 10a and 10c, showed cytotoxic activity below 10 mM in the NCI in vitro screen of 60 human tumor cell lines. The IC50 value of compound 10a was 6.8 mM and that of 10c, 8.3 mM. In addition, both compounds possessed differential activity against leukemia, colon and mammary cancer. The activity pattern was confirmed in two further screens using monolayer and clonogenic assays. In vivo antitumor studies showed that 10a was active against the human mammary carcinoma MT-1 and murine colon cancer MAC15A. Marginal activity was observed in human ovarian cancer model PXN/109T/C and the compound was inactive in human mammary cancer MCF-7. Conclusion: The results warrant further in vivo testing of 10a in additional human solid tumor models. The molecular modeling showed that the planarity of the chromophore and the side-chain conformation could assist the insertion of compound 10a between the base pairs of the double helix. On the other hand docking to the nucleotide sequence GGAATTGCCTCA suggested that the molecule could also act as a minor groove binder

Antitumor activity of imidazothioxanthones in murine and human tumor models in vitro and in vivo

Background: A new series of imidazothioxanthones has recently been synthesized as potential anticancer agents with the aim of overcoming drug resistance. The route of synthesis and DNA-binding properties of the compounds were reported previously. This paper describes the general structure-activity relationships for the class of imidazothioxanthones in panels of human and murine tumor cell lines in vitro, and the in vivo activity against human and murine solid tumors of the most potent compound, N-[3-(Dimethylamino)propylo]-11-oxo-11H-benzothiopyrano [3'2': 2, 3]pyrido[1,2-a] imidazo-2-carboxamide (10a). In addition, the interaction between compound 10a and DNA is also considered in terms of molecular mechanics methods and flexible docking techniques. Materials and Methods: The cytotoxicity of compounds 10a; 11-oxo-N-[2-(pyrrolidino)ethylo]-11H-benzothiopyrano [3',2':2,3]pyrido[1,2-a] imidazo-2-carbaramide, 11-oxo-N-[2-(piperidino)ethylo]-11H-benzothiopyrano [3',2':2,3]pyrido[1,2-a] imidazo-2-carboxamide and N-[2-(morpholino)ethylo]-11-oxo-11H-benzothiopyrano [3'2': 2, 3]pyrido[1,2-a]imidazo-2-carboxamide (10c-10e) was assessed in human tumor cell lines and xenografts using the sulforhodamine B assay, MTT assay and the clonogenic assay. The human ovarian xenograft, PXN/109TC, two human breast carcinomas, MT-1 and MCF-7, and the murine colon adenocarcinoma, MAC 15A were used for the in vivo testing of compound 10a. In addition, the interaction between compound 10a and DNA is also considered in terms of molecular mechanics methods and flexible docking techniques. Results: Two compounds, 10a and 10c, showed cytotoxic activity below 10 mM in the NCI in vitro screen of 60 human tumor cell lines. The IC50 value of compound 10a was 6.8 mM and that of 10c, 8.3 mM. In addition, both compounds possessed differential activity against leukemia, colon and mammary cancer. The activity pattern was confirmed in two further screens using monolayer and clonogenic assays. In vivo antitumor studies showed that 10a was active against the human mammary carcinoma MT-1 and murine colon cancer MAC15A. Marginal activity was observed in human ovarian cancer model PXN/109T/C and the compound was inactive in human mammary cancer MCF-7. Conclusion: The results warrant further in vivo testing of 10a in additional human solid tumor models. The molecular modeling showed that the planarity of the chromophore and the side-chain conformation could assist the insertion of compound 10a between the base pairs of the double helix On the other hand, docking to the nucleotide sequence GGAATTGCCTCA suggested that the molecule could also act as a minor groove binder