New organotin(IV) complexes with l-Arginine, Nα-t-Boc-l-Arginine and l-Alanyl-l-Arginine: Synthesis, structural investigations and cytotoxic activity

Abstract

Organotin(IV) NMR Cytotoxic activity a b s t r a c tNovel diorganotin(IV) derivatives of L-Arginine (HArg), N a -(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 0 )CO 2 H, where 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 a -t-Boc-L-Arginine complex, the N a -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 m(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.

An in vitro study on the effect of synthesized tin(IV) complexes on glioblastoma, colorectal, and skin cancer cell lines

“…We can interpret from these data that the various tin compounds share a property that affects processes common to all cancer cell lines (i.e., increased proliferation and aberrant apoptosis). Several researchers have reported that organotin(IV) complexes have the ability to induce apoptotic cell death [52]. However, the actual mechanism of this induced apoptosis of organotin(IV) compounds has not yet been determined.…”