New cytotoxic butyltin complexes with 2-sulfobenzoic acid: Molecular interaction with lipid bilayers and DNA as well as in vitro anticancer activity.

Abstract

New butyltin complexes with 2-sulfobenzoic acid: [Sn(C4H9)2{O3SC6H4COO-2}(H2O)]·(C2H5OH) (DBTsbz), [Sn(C4H9)3{O3SC6H4COOH-2}] (TBTsbz) and [Sn2(C4H9)6{μ-O3SC6H4COO-2}] (DTBTsbz) are very effective cytotoxic agents against tumor cells. The molecular interaction of these complexes with lipid membranes and DNA has been investigated. The IR spectra and changes of (1)H, (13)C chemical shifts suggest that SO3 and COO groups of 2-sulfobenzoato ligand interact with O atom of glycerin fragment of DPPC. Moreover, the compounds form Sn-OP bonds with phosphate groups of DPPC, which was shown by the lower frequency shift of the νs(PO2(-)) and νas(PO2(-)) band, by change of (31)P NMR signals and by DFT calculation. Another possibility is the interaction of the phosphate group of DPPC owing to formation of hydrogen bond O-H…O-P between water molecule coordinated to Sn and oxygen atom from the phosphate group. Using TCSPC-FCS we characterized DNA supramolecular assemblies' formation upon increasing TBTsbz, DTBTsbz and DBTsbz concentration. Diffusion time, lifetime and particle number changes are altered systematically with increasing Ccomp/CDNAbp ratio in following effectiveness order DBTsbz > TBTsbz > DTBTsbz. From those parameters we can conclude that all these compounds lead to a change of DNA winding, strand but not to DNA compaction. Investigated compounds show very high cytotoxic activity against cancer cell lines. All compounds exhibit efficient in vitro antitumor activity toward Jurkat (T-cell leukemia), CL-1 (T-lymphoblastoid cell line), GL-1 (B cell lymphoma cell line) and D-17 (canine osteosarcoma). The DBTsbz is more effective then carboplatin against canine osteosarcoma.

• Authors: Hanna Pruchnik, Teresa Kral, Dominik Poradowski, Aleksandra Pawlak, Angelika Drynda, Bożena Obmińska-Mrukowicz, Martin Hof
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 243 Pg. 107-18 (Jan 05 2016) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 26585592 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Benzenesulfonates
• Benzoates
• Lipid Bilayers
• Organotin Compounds
• mono-n-butyltin
• DNA
• 2-sulfobenzoic acid

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Benzenesulfonates (chemistry, pharmacology)
• Benzoates (chemistry, pharmacology)
• Cell Line, Tumor
• Crystallography, X-Ray
• DNA (chemistry, metabolism)
• Drug Screening Assays, Antitumor
• Humans
• Lipid Bilayers (chemistry, metabolism)
• Models, Molecular
• Neoplasms (drug therapy)
• Nucleic Acid Conformation (drug effects)
• Organotin Compounds (chemistry, pharmacology)