Biological Activity of Novel Organotin Compounds with a Schiff Base Containing an Antioxidant Fragment.

A series of novel organotin(IV) complexes on the base of 2-(N-3',5'-di-tert-butyl-4'-hydroxyphenyl)-iminomethylphenol (L) of formulae Me2SnBr2(L)2 (1), Bu2SnCl2(L)2(2), Ph2SnCl2(L) (3), Ph2SnCl2(L)2 (4) Ph3SnBr(L)2 (5) were synthesized and characterized by 1H, 13C, 119Sn NMR, IR, ESI-MS and elemental analysis. The crystal structures of initial L and complex 2 were determined by XRD method. It was found that L crystallizes in the orthorhombic syngony. The distorted octahedron geometry around Sn center is observed in the structure of complex 2. Intra- and inter-molecular hydrogen bonds were found in both structures. The antioxidant activity of new complexes as reducing agents, radical scavengers and lipoxygenase inhibitors was estimated spectrophotometrically in CUPRAC and DPPH tests (compounds 1 and 5 were found to be the most active in both methods), and in the process of enzymatic oxidation in vitro of linoleic acid under the action of lipoxygenase LOX 1-B (EC50 > 33.3 µM for complex 2). Furthermore, compounds 1-5 have been investigated for their antiproliferative activity in vitro towards HCT-116, MCF-7 and A-549 and non-malignant WI-38 human cell lines. Complexes 2 and 5 demonstrated the highest activity. The plausible mechanisms of the antiproliferative activity of compounds, including the influence on the polymerization of Tb+MAP, are discussed. Some of the synthesized compounds have also actively induced apoptosis and blocked proliferation in the cell cycle G2/M phase.

New Derivatives of Bacteriopurpurin with Thiolated Au (I) Complexes: Dual Darkand Light Activated Antitumor Potency.

BACKGROUND: Conventional antitumor Photosensitizers (PS) are normally low toxic in the dark whereas light activation triggers massive cell death (photodynamic therapy, PDT). OBJECTIVE: To expand the therapeutic potential of PS to dual potency cytocidal agents, taking advantage of the use of bacteriopurpurin for a deeper tissue penetration of light, and suitability of the tetrapyrrolic macrocycle for chemical modifications at its periphery. METHODS: Conjugation of a pro-oxidant thiolate Au (I) moiety to the bacteriopurpurin core and evaluation of cytotoxicity in cell culture and in vivo. RESULTS: New water-soluble derivatives showed micromolar cytotoxicity for cultured human tumor cell lines in the dark, including the subline with an altered drug response due to p53 inactivation. Cellular PDT with the selected conjugate, thiolate Au (I)-dipropoxybacteriopurpurinimide (compound 6) with two triphenylphosphine Au fragments, triggered rapid (within minutes) cell death. Damage to the plasma membrane (necrosis) was a hallmark of cell death by compound 6 both in the dark and upon light activation. Furthermore, one single i.v. injection of compound 6 caused retardation of transplanted syngeneic tumors at the tolerable dose. Illumination of tumors that accumulated compound 6 significantly synergized with the effect of 6 in the dark. CONCLUSION: Complexes of virtually non-toxic, photoactivatable bacteriopurpurin with the gold-containing organic moiety are considered the dual potency antitumor agents, tentatively applicable for intractable tumors.

Metal complexes with functionalised 2,2'-dipicolylamine ligand containing an antioxidant 2,6-di-tert-butylphenol moiety: synthesis and biological studies.

A series of Zn, Mn, Fe, Co, and Ni complexes ([MX2L], X = Cl, OAc) of the novel di-(2-picolyl)amine ligand L with an antioxidant 2,6-di-tert-butylphenol pendant were synthesized and characterized by elemental analysis, IR, multinuclear NMR spectroscopy, MALDI-TOF mass spectrometry and the molecular structures of [ZnCl2L] and [MnCl2L] were established by X-ray crystallography. The chemical oxidation of complexes with a 2,6-di-tert-butylphenol fragment to the phenoxyl radicals was studied by means of ESR method. The antioxidant radical scavenging activity of the complexes was measured spectrophotometrically using a DPPH-test and linoleic acid peroxidation. The electron transfer reactions were examined in CUPRAC tests and as the inhibition of an enzymatic reaction involving the generation of a reactive oxygen species (superoxide radical-anion) by xanthine oxidase. The lipoxygenase (LOX) inhibition activity of the studied compounds was evaluated. The in vitro biological experiments were performed by using rat brain homogenates. The role of the phenol fragment and metal was found to be essential in antioxidant activity.