Theses (MSc. Analytical & Pharmaceutical Chemistry)

The aim of this study was to synthesise and characterise nanogold-{[(Cu)(phen)(cys)(H2O)]NO3}n conjugate and to evaluate its antiproliferative property against breast cancer cell line (MCF7) and normal cell line (MCF10A). Nanogold solution was prepared using Turkevish method. In one approach, ternary copper(II) complex of 1,10-phenanthroline with amino acid L-cysteine, [(Cu)(phen)(cys)(H2O)]NO3, was first prepared and then tethered with the gold nanoparticles. In another approach, gold nanoparticles were reacted with L-cysteine, copper(II) nitrate, and 1,10-phenanthroline subsequently. The synthesized [(Cu)(phen)(cys)(H2O)]NO3 complex was characterised using fourier transform infrared (FTIR) and electrospray ionisation mass spectrometry (ESI-MS) techniques. FTIR and ESI-MS results show that L-cysteine was bound to the copper through carboxylic and amino groups, with the thiol moiety of L-cysteine remained free. The free thiol group bound to the nanogold surface to complete the nanogold-{[(Cu)(phen)(cys)(H2O)]NO3}n conjugate formation. Nanogold-{[(Cu)(phen)(cys)(H2O)]NO3}n conjugates were characterised using FTIR and UV-Vis spectroscopy. The increase in the surface plasmon absorption band in UV-Vis and absence of thiol peak in FTIR of the conjugate showed that the thiol group of L-cysteine was bound to the gold nanoparticle to form the conjugate. Moreover, the formation of the conjugate is also evidenced from the colour change from ruby red to blue. Anticancer property of the nanogold bound conjugate and unbound analogues was examined using MTS assay on breast cancer cell line (MCF7) and normal cell line (MCF10A). It was concluded that [Cu(phen)(cys)(H2O)]NO3 copper(II) complex was successfully prepared and tethered with nanogold particles. The prepared nanogold-{[(Cu)(phen)(cys)(H2O)]NO3}n conjugate was tested for its antiproliferative activity which showed better antiproliferative property towards the breast cancer cells than the unbound analogues.

Introduction: Photodynamic therapy is an alternative treatment to established standard treatments for cancer and antibiotics for bacterial infections. Although the potential of platinum-based drugs as antibacterial and anticancer agents has been studied for years, due to severe side effects that have limited their further development, ruthenium compounds are now emerging as one of the most promising therapeutic options in terms of targeting cancer and bacterial infections. Objectives: The objective of this work is to prepare and characterize a series of ruthenium complexes, followed by in vitro determination of their antibacterial and anticancer activity. Materials and Methods: Three ruthenium(II) Schiff base {[Ru(bpy)2(SB4CB)]PF6, [Ru(bpy)2(SBFH)]PF6, [Ru(bpy)2(SB4EB)]PF6} and two ruthenium(II) polypyridyl complexes { [Ru(bpy)2(bpy-COOH)](PF6)2, [Ru(bpy)2(bpy-(COOH)2)](PF6)2} were synthesized. FT-IR, UV-Vis, HPLC, NMR, ESI-MS, and elemental analysis were used to characterize the synthesized compounds. The antibacterial activity of the compounds was tested against susceptible strains of gram-negative bacteria Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922 (BSL 1), Acinetobacter baumannii ATCC 19606, and gram-positive Staphylococcus aureus ATCC 35923 (BSL 2). The anticancer activity of the compounds was tested against MDA-MB-231, A549, HT29, MeL28, SW1990 cancer cell lines, and non-cancerous MRC5 cell line. Finally, a combination study of the most promising compound with cisplatin was conducted to determine if there is synergistic anticancer effect. Results: [Ru(bpy)2(SB4CB)]PF6, and [Ru(bpy)2(SBFH)]PF6 were effective against Staphylococcus aureus, with MIC values of 16 μM when tested on irradiated plates and 16 μM and 8 μM, respectively, for non-irradiated plates. In the anticancer assay, SB4EB was active only in the MDA-MB-231 cell line with IC50 of 37.52 μM for light and 39.59 μM for dark. However, [Ru(bpy)2(bpy-COOH)](PF6)2 was inactive towards all the cell lines. The combination of [Ru(bpy)2(SB4CB)]PF6 with cisplatin did not show any synergistic effect on MDA-MB-231 and MeL28 cell lines, but an antagonistic effect was observed for the non-cancerous MRC5 cell line. Conclusion: [Ru(bpy)2(SB4CB)]PF6, and [Ru(bpy)2(SBFH)]PF6 exhibited favorable activity against Staphylococcus aureus. The most promising anticancer results were obtained for [Ru(bpy)2(SB4CB)]PF6 against MDA-MB-231 cell line. However, it’s combination with cisplatin did not show any synergistic effect on MDA-MB-231 and MeL28 cell lines.