Synthesis and characterization of novel [Pt(diimine) (acylthiourea)]+ complexes as potential anticancer agents and exploring the use of sulphobutyl-ether-B-cyclodextrin and surfactant micelles as a drug delivery system
Magwaza, Rachael Ntombikayise
A series of [Pt(diimine)(Ln-O,S)]Cl complexes, where Ln-O,S represents a series of N,N dialkyl-N’-acylthiourea ligands and diimine represents (1,10-Phenanthroline; 5,6-dimethyl 1,10-phenanthroline or [3,2-d:2’,3’-f]-quinoxaline were successfully synthesised and characterised. A new crystal structure was obtained for N,N-di(2-hydroxy)-N’ benzoylthiourea which revealed an interesting herringbone crystal packing arrangement. The cytotoxicity of the series of complexes was evaluated on H1975 lung cancer cell lines at 50 µM and 5 µM. All the complexes were highly cytotoxic with cell death of 90-98% at 50 µM. However, at 5 µM there were much more variations on cell viability percentages. Although the structure–activity relationship can only be established when the IC50 (the concentration of an inhibitor where the response is reduced by half) values are determined, it is clear that the complexes containing the methyl substituents on the 5 and 6 positions of the phenanthroline moiety were the most cytotoxic with almost 98% cell death at 5 µM. The solubility of the complexes did improve by using N,N-dialkyl-N’-acylthiourea as ancillary ligands, however aqueous solubility remains a major problem. Sulphobutyl-ether-β-cyclodextrin (captisol) and low-molecular-weight surfactant micelles as drug delivery systems were considered in attempt to improve the solubility. DOSY NMR Spectroscopy revealed that there was no inclusion complex formation between the complex and capstiol, although the chemical shift trend suggested that there is at least some interaction. The low-molecular-weight surfactant micelles were considered as an alternative, which showed some promise as a drug delivery system, since the aqueous solubility improved and a colloidal suspension was obtained.
A dissertation submitted to the Faculty of Science, University of the Witwatersrand, in fulfilment of the requirement for the degree Master of Science (MSc) in Chemistry. Johannesburg, March 2017.
Magwaza, Rachael Ntombikayise (2017) Synthesis and characterization of novel [Pt(diimine) (acylthiourea)]+ complexes as potential anticancer agents and exploring the use of sulphobutyl-ether-B-cyclodextrin and surfactant micelles as a drug delivery system, University of the Witwatersrand, Johannesburg, <http://hdl.handle.net/10539/24161>