1-1-diphenyl-2-picrylhydrazyl and selenourea

The stereoselective preparation of diosgenin-derived thio(seleno)ureas and glycomimetics bearing a 1,2,3-triazolyl tether on C-3 has been accomplished. The key steps in the synthetic pathway are the incorporation of an amino moiety and its further transformation into thio- and selenoureas, and also a click chemistry reaction involving a propargyl residue and an azido moiety to afford carbohydrate-derived 1,2,3-triazoles; subsequent BF3-promoted acetolysis of the spiranic moiety afforded the corresponding 22-oxocholestanic structure. The N-phenyl selenourea, an hitherto unknown steroidal derivative, turned out to be a potent ROS scavenger, in particular against free radicals (EC50 = 29.47 ± 2.33 μM, DPPH method), and as a glutathione peroxidase mimic in the elimination of H2O2 (t1/2 = 4.8 min, 1% molar ratio). 22-Oxocholestane structures bearing a C-3 azido, propargyl, thioureido, and particularly selenoureido moiety behaved as strong antiproliferative agents against HeLa cells (IC50 1.87-11.80 μM). N-phenyl selenourea also exhibited IC50 values lower than 6.50 μM for MDA-MB-231, MCF-7 and HepG2 cancer cells; apoptosis was found to be involved in its mode of action. Such compound was also capable of efficiently eliminating ROS endogenously produced by HeLa cells. Antiproliferative properties of thioxo and selenoxo derivatives were stronger than diosgenin.

Topics: Animals; Antineoplastic Agents; Biomimetic Materials; Biphenyl Compounds; Cell Line, Tumor; Cell Proliferation; Diosgenin; Drug Design; Drug Screening Assays, Antitumor; Free Radical Scavengers; Glutathione Peroxidase; Glycoconjugates; Humans; Mice; Organoselenium Compounds; Picrates; Reactive Oxygen Species; Triazoles; Urea

Ferrocene-incorporated selenoureas 1-(4-methoxybenzoyl)-3-(4-ferrocenylphenyl)selenourea (P4Me), 1-(3-methoxybenzoyl)-3-(4-ferrocenylphenyl)selenourea (P3Me), and 1-(2-methoxybenzoyl)-3-(4-ferrocenylphenyl)selenourea (P2Me) were synthesized and characterized by nuclear magnetic resonance, Fourier transform infrared spectroscopy, atomic absorption spectroscopy, CHNS, and single-crystal X-ray diffraction. DNA interaction of the compounds was investigated with cyclic voltammetry, UV-visible spectroscopy, and viscometry, which is a prerequisite for anticancer agents. Drug-DNA binding constant was found to vary in the sequence: K(P4Me) (4.9000 × 10⁴ M⁻¹) > K(P2Me) (2.318 × 10⁴ M⁻¹) > K(P3Me) (1.296 × 10⁴ M⁻¹). Antioxidant (1,1-diphenyl-2-picrylhydrazyl), antifungal (against Faussarium solani and Helmentosporium sativum), and antibacterial (against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis) activities have also been reported in addition.

Topics: Anti-Bacterial Agents; Antifungal Agents; Antioxidants; Bacteria; Biphenyl Compounds; Crystallography, X-Ray; DNA; Electrochemical Techniques; Ferrous Compounds; Free Radical Scavengers; Fungi; Metallocenes; Microbial Sensitivity Tests; Models, Molecular; Organoselenium Compounds; Picrates; Urea