Synthesis and cytotoxic activity of organotin(IV) diallyldithiocarbamate compounds as anticancer agent towards colon adenocarcinoma cells (HT-29)

Abstract

Context: Diphenyltin(IV) diallyldithiocarbamate compound (Compound 1) and triphenyltin(IV) diallyldithiocarbamate compound (Compound 2) are two newly synthesised compounds of organotin(IV) with diallyldithiocarbamate ligands. Objective: To assess the cytotoxic effects of two synthesised compounds against HT-29 human colon adenocarcinoma cells and human CCD-18Co normal colon cells. Materials and methods: Two successfully synthesised compounds were characterised using elemental (carbon, hydrogen, nitrogen, and sulphur) analysis, Fourier-Transform Infrared (FTIR), and 1H, 13C 119Sn Nucleus Magnetic Resonance (NMR) spectroscopies. The single-crystal structure of both compounds was determined by X-ray single-crystal analysis. The cytotoxicity of the compounds was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazholium bromide (MTT) assay upon 24 h of treatment. While the mode of cell death was determined based on the externalisation of phosphatidylserine using a flow cytometer. Results: The elemental analysis data of the two compounds showed an agreement with the suggested formula of (C6H5)2Sn[S2CN(C3H5)2]2 for Compound 1 and (C6H5)3Sn[S2CN(C3H5)2] for Compound 2. The two major peaks of infrared absorbance, i.e., ν(C = N) and ν(C = S) were detected at the range of 1475–1479 cm−1 and 972–977 cm−1, respectively. The chemical shift of carbon in NCS2 group for Compound 1 and 2 were found at 200.82 and 197.79 ppm. The crystal structure of Compound 1 showed that it is six coordinated and crystallised in monoclinic, P21/c space group. While the crystal structure of Compound 2 is five coordinated and crystallised in monoclinic, P21/c space group. The cytotoxicity (IC50) of the two compounds against HT-29 cell were 2.36 μM and 0.39 μM. Meanwhile, the percentage of cell death modes between 60% and 75% for compound 1 and compound 2 were mainly due to apoptosis, suggesting that both compounds induced growth arrest. Conclusion: Our study concluded that the synthesised compounds showed potent cytotoxicity towards HT-29 cell, with the triphenyltin(IV) compound showing the highest effect compared to diphenyltin(IV).

Keywords

• Organotin(IV)
• Diallyldithiocarbamate
• HT-29
• CCD-18Co
• Cytotoxicity
• Apoptosis