Organometallic complexes with biological molecules. XIV. Biological activity of dialkyl and trialkyltin(IV) [meso-tetra(4-carboxy- phenyl)porphinate] derivatives

Abstract

The effects of several organotin(IV) meso‐tetra(4‐carboxyphenyl)porphinate] derivatives with the general formula (R2Sn)2TPPC and (R3Sn)4TPPC (R = Me, Bu, Ph) were tested in vivo on ascidian embryonic development. Embryos at the two‐cell stage were incubated in 1 × 10−5 or 1 × 10−7 M solutions of various compounds. The ligand, [meso‐tetra(4‐carboxyphenyl)porphine] (H4TPPC) was toxic at 1 × 10−5 M, because development was blocked at an early gastrula stage, whereas 1 × 10−7 M H4TPPC allowed the eggs to develop up to the larva stage. The most toxic among the tested compounds was tributyltin(IV) [meso‐tetra(4‐carboxyphenyl)porphinate], (Bu3Sn)4TPPC, since the fertilized eggs were unable to divide into two cells, even at a concentration of 1 × 10−7 M. To correlate this embryonic arrest with the metabolic pathway, and especially to understand why cellular organelles first underwent chemical damage, 10−5 and 10−7 M (Bu3Sn)4TPPC‐cultured fertilized eggs were tested for DNA, RNA, protein, glucose, lipid and ATP contents, comparing the values obtained with those of control culture fertilized egg contents. The higher concentration (1 × 10−5 M) reduced the content of all the tested compounds, but the lower one (1 × 10−7 M), even if still unable to allow cleavage, reduced only the lipids and the ATP contents. A hypothesis concerning initial damage to mitochondrial membrane is proposed. Copyright © 2000 John Wiley & Sons, Ltd.

Synthesis, structural investigations on organotin(IV) chlorin-e6 complexes, their effect on sea urchin embryonic development and induced apoptosis

“…Furthermore, attention has been addressed on the interaction with DNA of newly synthesized compounds [6,10,12] and on the antineoplastic effect of several organotin(IV) compounds [13][14][15].…”

“…On the other hand, the biological effects of organotin(IV) derivatives have been the focus of research in embryos and gametes of Ascidians [7,10,11]. Furthermore, attention has been addressed on the interaction with DNA of newly synthesized compounds [6,10,12] and on the antineoplastic effect of several organotin(IV) compounds [13][14][15].…”

Toxicity of Organic Compounds to Marine Invertebrate Embryos and Larvae: A Comparison Between the Sea Urchin Embryogenesis Bioassay and Alternative Test Species

“…However, those data mainly correspond to adult stage animals and chronic exposure conditions. Reported effects of TBT in ascidian and sea urchin embryos and larvae include inhibition of the oxidative phosphorylation in the mitochondria and impairing of the intracellular Ca +2 homeostasis (Cima et al, 1996a(Cima et al, , b, 1998Girard et al, 1997Girard et al, , 2000Mansueto et al, 2000). Furthermore, Lignot et al (1998) reported effects of TBT on the osmoregulatory capacity of crustacean larvae.…”

“…Moreover, Girard et al (2000) obtained toxic effects on larval survival and growth of P. lividus larvae after exposure of eggs to 0.03-0.3 lg l )1 of TBT, suggesting that concentrations of TBT with no effect on the embryonic development could affect the sea urchin larval cycle and metamorphosis. Organoestanic compounds like TBT have been found to damage the embryonic and larval development of Ciona intestinalis in the 0.1-10 lM concentration range (Mansueto et al, 1993a, b;Maggio et al, 1994;Gianguzza et al, 1996;Pellerito et al, 1997Pellerito et al, , 1998Mansueto et al, 2000). In contrast, our results showed toxic effects of TBT at concentrations of a nanomolar range (EC 50 = 22 nM), although the incubation times in our toxicity tests are higher (20 h).…”

Apoptosis and cell growth arrest in A375 human melanoma cells by diorganotin(IV) and triorganotin(IV) complexes of [meso-Tetra(4-sulfonatophenyl)porphine] manganese(III)chloride

“…As previously showed, these compounds as well as other similar porphyrin derivatives have a photo-independent cytotoxic effect (14)(15)(16)(17). In fact, we demonstrated that (Bu 2 Sn) 2 TPPS and (Bu 3 Sn) 4 TPPS compounds induce the apoptotic death of A375 human melanoma cells without being irradiated (18), causing an arrest of cell proliferation as well, when used at lower concentrations (19).…”