Diphenyltin(IV) dithiocarbamate macrocyclic scaffolds as potent apoptosis inducers for human cancer HEP 3B and IMR 32 cells: synthesis, spectral characterization, density functional theory study and<i>in vitro</i>cytotoxicity

Abstract

Binuclear diphenyltin(IV) dithiocabamate macrocyclic complexes [(Ph 2 Sn IV ) 2 ‐μ 2 ‐bis{(κ 2 S , S ‐S 2 CN(R)CH 2 CONHC 6 H 4 ) 2 O}] (R = i Pr ( 1 ), s Bu ( 2 ), n Bu ( 3 ), Cy ( 4 ), 2‐furfuryl ( 5 ) or benzyl ( 6 )) were synthesized through a self‐assembly process involving novel diamino precursors 4,4′‐bis(2‐(alkylamino)acetamido)diphenyl ethers ( L 1 , L 2 , L 3 , L 4 , L 5 , L 6 ), CS 2 and Ph 2 SnCl 2 . These were characterized using microanalysis and relevant spectroscopic methods. The geometry of all compounds was optimized using the density functional theory method. In vitro cytotoxic activity was evaluated against HEP 3B (hepatoma) and IMR 32 (neuroblastoma) using the MTT assay. Notably, complexes 1 , 2 , 3 , 4 , 5 , 6 were found to be extremely active against both cell lines and cytotoxicity data confirmed their 16‐fold better potency compared to cisplatin, a well‐known antineoplastic drug. Flow cytometric analysis of annexin V–propidium iodide‐stained cells demonstrated the ability of L 5 , 4 and 6 to induce apoptosis in HEP 3B and IMR 32 cells, required for major therapeutic implication in cancer therapy. The extraordinary potency of binuclear complex 4 can be correlated with higher LUMO energy together with the greatest value of residual charge on the Sn(IV) centre among the compounds under investigation. Copyright © 2015 John Wiley &amp; Sons, Ltd.