117,607 research outputs found
Porphyrin tributyltin(IV) complexes for a novel approach in the tratment of human melanoma
No full textMelanoma is the most deadly form of skin cancer, largely refractory to existing therapies.
The study of porphyrin derivatives as potential anti-tumor drugs has been an interesting field
of investigation in the last years. Recently, a photo-independent cytotoxic effect of
(Bu3Sn)4TPPS in the blocking melanoma cell proliferation an inducing a morphology cell
change was investigated.[1] Amphiphilic CD (ACyD) provides more water soluble and
adaptable nanovectors through modulation of the balance between hydrophobic and
hydrophilic chains at both CD sides. ACyD can be conveniently tailored by covalently
appending fluorescent label or receptor-targeting glycosyl- groups and can encapsulate
conventional and phototherapeutic drugs.[2] The aim of this work was to design biomimetic
nanoassemblies based on non-ionic and hydrophilic ACyD (SC6OH) for delivery of poor
water soluble organotin(IV)-porphyrin complexes in melanoma cancer cell. Nanoassemblies
were prepared by dispersion in water of (Bu3Sn)4TPPS/SC6OH organic film at 1:5 molar ratio
and characterized by a combination of spectroscopic and morphological techniques. Size
distribution, charge, drug encapsulation efficiency and in vitro release were investigated.
Intracellular delivery, cytotoxicity, nuclear morphology and cell growth kinetics were
evaluated by fluorescence microscopy on A375 human melanoma cells. UV-vis and emission
spectroscopy of (Bu3Sn)4TPPS/SC6OH show shifts of the peculiar bands of organotin(IV)-
porphryin complex by interaction with supramolecular nanoaggregates of ACyD in aqueous
solution. Mean size was within the range 100-120 nm. ξ-potential was negative for all the
formulations (–16 mV in (Bu3Sn)4TPPS/SC16OH system with loading capacity of 18%).
Delivering of (Bu3Sn)4TPPS by ACyD with respect to free (Bu3Sn)4TPPS provoke a more
efficient internalization, a higher cytotoxic effect inducing apoptotic cell death and at lower
concentrations a cellular morphology change blocking cell proliferation. In conclusion the
strategy of entrapping anticancer drug based on poor water-soluble porphyrin organotin
complexes in ACyD nanocarriers is here proposed as new photo-independent therapeutic
approaches against melanoma.
References
[1] M.A. Costa, F. Zito, M.R. Emma, L. Pellerito, T. Fiore, C. Pellerito, G. Barbieri, Int. J. Oncol. 2011, 38,
693.
[2] A. Mazzaglia, Photodynamic Tumor Therapy with Cyclodextrin Nanoassemblies. In: Cyclodextrins in
Pharmaceutics, Cosmetics, and Biomedicine: Current and Future Industrial Applications, E. Bilensoy
(Ed.); John Wiley & Sons, Inc.: Hoboken, 2011; pp. 343-361
Diorganotin(IV) N-acetyl-L-cysteinate complexes: Synthesis, solid state, solution phase, DFT and biological investigations.
No full textDiorganotin(IV) complexes of N-acetyl-L-cysteine (H2NAC; (R)-2-acetamido-3-sulfanylpropanoic acid) have
been synthesized and their solid and solution-phase structural configurations investigated by FTIR,
Mössbauer, 1H, 13C and 119Sn NMR spectroscopy. FTIR results suggested that in R2Sn(IV)NAC (R=Me, Bu,
Ph) complexes NAC2− behaves as dianionic tridentate ligand coordinating the tin(IV) atom, through estertype
carboxylate, acetate carbonyl oxygen atom and the deprotonated thiolate group. From 119Sn Mössbauer
spectroscopy it could be inferred that the tin atom is pentacoordinated, with equatorial R2Sn(IV) trigonal
bipyramidal configuration. In DMSO-d6 solution, NMR spectroscopic data showed the coordination of one
solvent molecule to tin atom, while the coordination mode of the ligand through the ester-type carboxylate
and the deprotonated thiolate group was retained in solution. DFT (Density Functional Theory) study
confirmed the proposed structures in solution phase as well as the determination of the most probable stable
ring conformation. Biological investigations showed that Bu2SnCl2 and NAC2 induce loss of viability in HCC
cells and only moderate effects in non-tumor Chang liver cells. NAC2 showed lower cytotoxic activity than
Bu2SnCl2, suggesting that the binding with NAC2− modulates the marked cytotoxic activity exerted by
Bu2SnCl2. Therefore, these novel butyl derivatives could represent a new class of anticancer drugs
Bu2Sn(N-acetyl-L-cysteinate) antitumor activity on HepG2 cells
No full textMany drugs currently used in anticancer therapies, act by activating cytotoxic death by apoptosis. This death mechanism is often accompanied by mitochondrial events (intrinsic apoptosis) or the activation of death receptors (extrinsic pathway
Biological activity studies on organotin(IV)n+ complexes and parent Compounds
No full textThis review summarized the literature and own data on the parent organotin(IV) compounds and complexes formed with biologically active ligands
Organotins as mitochondria toxins.
No full textFrom the synthesis of the first organotin, in mid nineteenth century, and the amazing discovery of a wide spectrum of exploitations and industrial uses of these man-made chemicals in the subsequent century, the dark side of organotins increasingly came out in the second half of the twentieth century. Organotins now represent a matter of environmental concerns, for the toxic effects displayed on a wide spectrum of organisms, from bacteria to humans, and for the global contamination, especially of water basins which act as reservoirs. Unfortunately, but realistically, contamination and worries are fated to persist, due to the environmental persistency and high bioaccumulation potential of these pollutants. In spite of the wealth of studies, the intimate mechanisms of the toxic action of organotin compounds are not entirely established and our knowledge needs to be continuously reviewed and updated. This e-book aims at gathering the emerging data on organotin effects on animals, with special focus on their biochemical interactions with biomolecules, on which toxicity mechanisms are often founded. Chapter by chapter, the biological and biochemical effects of organotins are unravelled by a careful analysis of the most recent findings, paying special attention to the contaminant action mechanisms at cellular and molecular level.
In the first chapter, the legislation on organotin-based antifouling paints and organotin contamination levels of aquatic environments are carefully reviewed. Special attention is paid to the most known toxic effect, namely imposex, which is a irreversible superimposition of male-type genitalia in female gastropod mollusks. Imposex mirrors environmental concentrations of the most toxic organotins.
The structural and chemical properties of toxic organotin compounds are carefully examined in Chapter 2, with special focus on their biological and pharmacological activities.
In Chapter 3 the recent discovery of direct high affinity interactions between trialkyltins and the family of nuclear hormone receptors which function as ligand dependent transcription factors for lipophilic endocrine hormones in vertebrates and invertebrates is presented.
Studies on the interactions of organotins with model and natural biological membranes are reported in Chapter 4.
The ability of organotins to act as endocrine-disrupting chemicals is considered in Chapter 5, focusing on TBT- induced imposex in neogastropods.
Chapter 6 embraces the most recent knowledge on the molecular and biochemical mechanisms involved in lipid homeostasis disruption within several metazoan phyla, from mollusks to amphibians, teleosts and mammals.
In Chapter 7 the organotin-driven genotoxicity and immunotoxicity, which among toxic effects are the most important in affecting survival, are reviewed in mammals, fish and aquatic invertebrates.
Effects on mitochondria, one of the main targets of organotins are considered in Chapter 8. The impairment of mitochondrial functions and the consequent ATP synthesis depletion may play a crucial role as molecular basis of several toxic effects of organotins.
Chapter 9 reviews the impact of organotin exposure on fresh- and seawater organisms of various phyla by examining the histophathological, physiological and molecular interactions of organotin compounds with relevant enzymes, membranes, the endocrine system, and the consequential ramifications for individuals, populations and community structure in aquatic ecosystems.
Recent research on the mechanisms of organotin-induced apoptosis is reviewed in Chapter 10. The modulation of apoptosis, involved in ontogenesis, development and cell turnover, is a critical step of cellular toxicity.
Chapter 11 reviews the impacts of organotins on humans and presents major applications of organotins, their entry in the food chain, human exposure and effects of organotins.
Once overviewed the broad susceptibility to organotins in literature data, Chapter 12 underlines the astonishing analogies of the toxic action of these chemicals in animal kingdom on one hand and on the other, the variegated toxicity displayed in different cells, tissues and species
Effects of tri-n-butyltin(IV) chloride on neurulation of Ciona intestinalis (Tunicata, Ascidiacea): an ultrastructural study
No full textThis paper reports the cytotoxic effects of tri-n-butyltin (IV) chloride, TBTCl, on the neurulation
process of the ascidian Ciona intestinalis. Exposure of the embryos at early neurula stage in 10−5 and
10−7 M TBT (IV) chloride solutions for 1–2 h provoked the irreversible arrest of their development.
Morphological and ultrastructural observations suggested that most probably there are two principal
causes determining the neurulation process block. The first is due to the TBT effects of inhibiting
the polymerization and/or degradation of microfilaments and microtubules, proteins that constitute
the cytoskeleton. The lack of orientation and extension of both microtubules and microfilaments
of actin prevent the shape changes and mobility of neural plate blastomeres indispensable to the
neurulation process. The second cause is certainly determined by the ultrastructural modification
whichmitochondria undergo. The ultrastructural anomalies showed by these organules are so serious
as to impede their proper functionality with consequent inhibition of oxidative phosphorylation and
ATP synthesis, remarkable metabolic processes that occur during ascidian neurulation
Coordination Properties of an ACE Inhibitor, Captopril Towards Me2Sn(IV)2+ in Aqueous Solution and Biological Aspects of Some Dialkyltin(IV) Derivatives of This Ligand
No full textSynthesis, structural investigations on organotin(IV) chlorin-e6 complexes, their effect on sea urchin embryonic development and induced apoptosis
No full textFour new organotin(IV) chlorin derivatives, [chlorin = chlorin-e6 = 21H,23H-porphine-2-propanoic acid, 18-carboxy-20-(carboxymethyl)-
8-ethenyl-13-ethyl-2,3-di-hydro-3,7,12,17-tetramethyl-(2S-trans)–], with formula (R2Sn)3(chlorin)2 Æ 2H2O (R = Me,
n-Bu) and (R3Sn)3chlorin Æ 2H2O (R = Me, Ph) have been synthesized. The solid state and solution phase structures have been investigated
by FT-IR, 119Sn Mo ̈ssbauer, 1H and 13C NMR spectroscopy. In the solid state, (R2Sn)3(chlorin)2 Æ 2H2O complexes contain
six coordinated Sn(IV), in a skew trapezoidal environment by forming trans-R2SnO4 polymeric units. As far as (R3Sn)3chlorin
Æ 2H2O complexes are concerned, Sn(IV) is five coordinated in a polymeric (oligomeric) trigonal bipyramidal environment
and eq-R3SnO2 units, in the solid state. In saturated solutions, a polymeric structure comparable to the solid phase, with carboxylate
groups of the ligand behaving in monoanionic bidentate fashion bridging Sn(IV) atoms, was detected for the (Me3Sn)3chlorin
Æ 2H2O complex, while in more diluted ones a tetrahedral configuration for the trimethyltin(IV) moieties was observed.
Cytotoxic activity of the novel organotin(IV) chlorin was investigated in order to assay the effect on sea urchin embryonic development.
The results obtained demonstrated that (n-Bu2Sn)3(chlorin)2 Æ 2H2O and (Ph3Sn)3chlorin Æ 2H2O exerted the antimitotic
effect on the early stages of sea urchin development. In addition, the cytotoxic effect exerted by (n-Bu2Sn)3(chlorin)2 Æ 2H2O
appeared with necrosis of the blastomeres, which were clearly destroyed. After treatment with (Ph3Sn)3chlorin Æ 2H2O, a programmed
cell death was triggered, as shown by light microscope observations through morphological assays. The apoptotic events
in 2-cell stage embryos revealed: (i) DNA fragmentation, with the TUNEL reaction (terminal deoxynucleotidyl transferase-mediated
dUTP nick end labelling); (ii) phosphatidylserine translocation in the membrane, with Annexin-V assay and (iii) cytoplasm blebbing,
with the TUNEL reaction. The results demonstrated that the novel compound (Ph3Sn)3chlorin Æ 2H2O was the most toxic derivative,
by exerting antimitotic effect very early and by triggering apoptosis in the 2-cell stage of sea urchin embryonic development
Effects of two organotin(IV)(sulfonato phenyl)porphynates on the MAPKs and on the growth of A375 human melanoma cells
No full textPreviously we showed apoptotic induction in A375 human melanoma cells using two complexes of the mesotetra(4-sulfonatophenyl)porphinate (TPPS),(Bu2Sn)2TPPS and (Bu3Sn)4TPPS.
To understand how these compounds
activate apoptosis in melanoma cells we studied MAPKs and the (Bu2Sn)TPPS and (Bu3Sn)4TPPS cellular uptake.
Western blotting experiments showed activated protein kinases ERK 1/2, JNK and p38 in 10 μM (Bu2Sn)2TPPS- and 1 μM (Bu3Sn)4TPPS-treated melanoma cells, which suggests
that the three MAP kinases are involved in the apoptotic death of A375-treated cells. By taking advantage of the porphyrin
fluorescence, we found a fast concentration of (Bu2Sn)2TPPS and (Bu3Sn)4TPPS in the nucleus and in the nucleoli compared
to TPPS. A significantly reduced growth of A375 human melanoma cells was also observed after only 48 h treatment by using 500 nM of (Bu2Sn)2TPPS or 80 nM of (Bu3Sn)4TPPS.
A strong slowdown of cell growth and loss of cell-cell interactions were visible by in vitro wound repair assay
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