An In Vitro Study of the Effect of Cytotoxic Triorganotin Dimethylaminophenylazobenzoate Complexes on Red Blood Cells

Abstract

Interactions of tributyltin (TBTA) and triphenyltin (TPhTA) 2-[4 (dimethylamino)phenylazo]benzoates, showing promising cytostatic activity against tumor cells, with erythrocytes and with erythrocyte membranes and model lipid membranes have been investigated. The effect of TBTA and TPhTA on the erythrocyte and its model membrane was investigated by the microscopic and spectroscopic methods. Interaction of tin complexes with the membrane was determined on the basis of hemolytic activity, changes induced in the shape of erythrocytes, as well as physicochemical parameters of the membrane, such as fluidity. The studies showed that the compounds in higher concentration induce hemolysis; however, TBTA is more toxic than TPhTA. Both TBTA and TPhTA induce morphological alterations in red blood cells-from discocytes to spherocytes and from discocytes to echinocytes. The results suggest that investigated complexes interact with the erythrocyte membrane, change its properties, and probably locate themselves in the hydrophilic part of the membrane, which agrees with conclusions drawn from investigation of erythrocyte membranes and model lipid membranes with the help of fluorescence and infrared spectroscopy.

Keywords: Cell membrane; Erythrocyte; Hemolytic activity; Microscopy; Spectroscopy; Triorganotin compounds.

Fig. 1

Chemical structure of TBTA and TPhTA

Fig. 2

The dependence of percentage of erythrocyte hemolysis on the concentration of tributyltin and triphenyltin complexes

Fig. 3

Photographs of red blood cells modified with TTA complexes at 8 µM, obtained with an electron microscope: control (a), TBTA (b), TPhTA (c)

Fig. 4

Differences in values of generalized polarization (GP) of the Laurdan probe for RBCM and RBCL modified with triorganotin complexes at 37 °C

Fig. 5

Fluorescence emission spectra of MC540 in pure RBCM (solid line) and modified with 8 µM TTA (dashed lines)

Fig. 6

FTIR spectra of RBCM pure (solid line) or containing incorporated organometallic compounds (thin line): a symmetric and asymmetric CH₂ stretching band, b phosphate band I (asymmetric vibration), c phosphate band II (symmetric vibration), d choline band

Fig. 7

Probable bond between oxygen atom of phosphate group of phospholipid and tin atom of SnBu₃(OOCR) complex