Dibutyltin(IV) complexes derived from L-DOPA: synthesis, molecular docking, cytotoxic and antifungal activity

Abstract

A series of organotin(IV) complexes was herein prepared and characterized. A one-pot synthetic strategy afforded reasonable to high yields, depending on the nature of the ligand. All new complexes were fully characterized by spectroscopic techniques, consisting of IR, MS and NMR (1H, 13C and 119Sn). The in vitro cytotoxicity tests demonstrated that the organotin complexes produced a greater inhibition, versus cisplatin (the positive control), of the growth of six human cancer cell lines: U-251 (glioblastoma), K-562 (chronic myelogenous leukemia), HCT-15 (colorectal), MCF-7 (breast), MDA-MB-231 (breast) and SKLU-1 (non-small cell lung). The potency of this cytotoxic activity depended on the nature of the substituent bonded to the aromatic ring. All complexes exhibited excellent IC50 values. The test compounds were also screened in vitro for their antifungal effect against Candida glabrata and Candida albicans, showing MIC (minimum inhibitory concentration) values lower than those obtained for fluconazole. A brine shrimp bioassay was performed to examine the toxic properties. Molecular docking studies demonstrated that the organotin(IV) complexes bind at the active site of topoisomerase I in a similar manner to topotecan, sharing affinity for certain amino acid side chains (Ile535, Arg364 and Asp533), as well as for similar DNA regions (DA113, DC112 and DT10).