New organotin(IV) complexes with L-Arginine,Nα-t-Boc-L-Arginine and L-Alanyl-L-Arginine.Synthesis, structural investigations and cytotoxic activity
| Autor: | Giuseppe Calvaruso, Patrizia Portanova, Giuseppe Ruisi, Simona Rubino, M. Assunta Girasolo, Giancarlo Stocco |
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| Přispěvatelé: | Girasolo, MA, Rubino, S, Portanova, P, Calvaruso, G, Ruisi, G, Stocco, G |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Arginine
Stereochemistry Ligand Organic Chemistry L-Arginine Boc-Arg-OH L-Alanyl-L-Arginine organotin(IV) NMR cytotoxic activity Substrate (chemistry) Biological activity Biochemistry Inorganic Chemistry chemistry.chemical_compound chemistry Settore CHIM/03 - Chimica Generale E Inorganica Materials Chemistry Chelation Carboxylate Physical and Theoretical Chemistry Cytotoxicity Two-dimensional nuclear magnetic resonance spectroscopy |
| Popis: | Novel diorganotin(IV) derivatives of l -Arginine (HArg), N α -( tert -Butoxycarbonyl)- l -Arginine (Boc–Arg–OH) and l -Ala- l -Arg (H 2 Ala–Arg), H 2 NC( NH)NH(CH 2 ) 3 CH(NHR′)CO 2 H, where R′ = H in HArg, R′ = C(O)OC(CH 3 ) 3 in Boc–Arg–OH, R′ = H 2 NCH(CH 3 )CO in H 2 Ala–Arg and triorganotin(IV) derivatives of Boc–Arg–OH have been synthesized and structurally characterized. The complexes were investigated by FT-IR and 119 Sn Mossbauer in the solid state and by 1 H, 13 C, 119 Sn and 1 H– 1 H COSY NMR spectroscopy, in solution. The spectroscopic characterization leading to the proposed molecular structures was accomplished on the basis of these experiments. l -Arginine appears to behave as a chelating ligand through carboxylate and -NH 2 groups in Me 2 Sn(Arg) 2 , while in N α - t -Boc- l -Arginine complex, the N α -protected amino group being exempted from coordination, only the carboxylate groups are effectors of bonding to the organometallic moieties. FT-IR spectra give a clear indication that guanidino groups in all the complexes are not involved in coordination, since ν (C N–H) frequency of the terminal guanidino group is fairly constant and unshifted relative to the free ligand. The biological activity of organotin(IV)-complexes was also investigated by use of human HT29 colorectal carcinoma cells. The cytotoxic activity of the compounds was determined by the MTT quantitative colorimetric assay, capable of detecting viable cells in comparison with that exerted by cisplatin. A marked cytotoxic activity for nearly all complexes, is evident being higher than that exerted by cisplatin, while no significant improvement of activity was observed for Me 2 Sn(Arg) 2 and Me 2 Sn(Ala–Arg), which was confirmed by IC 50 values. Then, we assessed whether the cytotoxicity induced by organotin(IV) complexes was associated with the induction of apoptosis. Light microscopy analysis, performed to study the morphological changes induced in HT29 cells, confirmed the results obtained with MTT test. No significant morphological alterations were observed in HT29 cells after treatment with Me 2 Sn(Ala–Arg) and Me 2 Sn( l -Arg) 2 . Cells treated with n Bu 2 Sn(Boc–Arg) 2 , n Bu 2 Sn(Ala–Arg), n Bu 3 Sn(Boc–Arg) and Me 3 Sn(Boc–Arg), appeared rounded, isolated and detached from culture substrate, indicating the commitment to apoptotic cell death. |
| Databáze: | OpenAIRE |
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