We synthesized, characterized and tested in a panel of cancer cell lines, nine new bipyridine gold(III) dithiocarbamate-containing complexes. In vitro studies demonstrated that compounds 1, 2, 4, 5, 7 and 8 were the most cytotoxic in prostate, breast, ovarian cancer cell lines and in Hodgkin lymphoma cells with IC50 values lower than the reference drug cisplatin. The most active compound 1 was more active than cisplatin in ovarian (A2780cis and 2780CP-16) and breast cancer cisplatin-resistant cells. Compound 1 determined an alteration of the cellular redox homeostasis leading to increased ROS levels, a decrease in the mitochondrial membrane potential, cytochrome-c release from the mitochondria and activation of caspases 9 and 3. The ROS scavenger NAC suppressed ROS generation and rescued cells from damage. Compound 1 resulted more active in tumor cells than in normal human Mesenchymal stromal cells. Gold compounds were active independent of p53 status: exerted cytotoxic effects on a panel of non-small cell lung cancer cell lines with different p53 status and in the ovarian A2780 model where the p53 was knocked out. In conclusion, these promising results strongly indicate the need for further preclinical evaluation to test the clinical potential of these new gold(III) complexes.

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Four new gold(i) complexes were synthesized and characterized. The structure of [t-Bu3PAuS2CN(C7H7)2] was determined by X-ray diffraction.

Synthesis, characterization and anticancer activity of gold(I) complexes that contain tri-tert-butylphosphine and dialkyl dithiocarbamate ligands This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. KAUST Repository M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPTTwo new linear gold(I) complexes of formulae [Au{P(t-Bu) 3 }(S 2 CN(CH 3 ) 2 )] (2), and [Au{P(tBu) 3 }(S 2 CN(C 2 H 5 ) 2 )] (3) have been prepared. The structure of these complexes have been determined by single X-ray crystallography. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPTCorresponding author Dr. A. A. Isab (aisab@kfupm.edu.sa) 32 M A N U S C R I P T A C C E P T E D 127The C=S thiocarbonyl stretch splits into two peaks (doublet) at 1022, 972 cm -1 and 1020, 989128 cm -1 with medium intensity in the spectra of complexes (2) and ( 142The band at 304 cm -1 in the far-IR spectrum of complex (1) Table 2. A small upfield shift for methyl protons of tri-ter-butyl group was observed 148 for complex (2) compared to complex (1). Whereas, a small downfield shift for methyl protons 149 of tri-ter-butyl group have been observed for complex (3) as shown in X-ray structure of complex (3) is shown in Figure 2. There are two independent molecules of 181 gold(I) complex in the asymmetric unit cell. In both molecules, gold(I) atom is coordinated with 182 one P donor atom of tri-ter-butylphosphine ligand and S atom of diethyl dithiocarbamate ligand. 183There are only minor conformational differences between x-ray structure of two molecules. 184The Au1-S1 and Au2-S3 bond distances are 2.3293 (15) 1.04 µM as given in Table 4. 227The in vitro cytotoxicity in terms of IC 50 values against A549 cell line were found 41.60 ± 3.00, were applied using the SCALE3 ABSPACK [68]. Graphics were generated using PLATON [69]. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 296A summary of crystal data and refinement details for gold(I) complexes (2) and (3) are given in 297 Table 5. Selected bond lengths and bond angles are given in Table 6. Res. 66 (2006) labelling scheme and displacement ellipsoids drawn at 50% probability level. • Gold(I) complexes of the type P-Au(I)-S were synthesized.• Cytotoxicity of complexes measured on A549, HeLa and MCF7 cell lines.• X-ray data shows the gold coordination sphere adopts a linear geometry Control 100.9 ± 2.9 98.7 ± 2.7 99.8 ± 2.43.12 93.6 ± 2.4 50.6 ± 1.5 53.9 ± 1.96.25 89.5 ± 2.3 34.4 ± 0.9 38.6 ± 1.2 12.5 81.9 ± 1.9 19.5 ± 1.4 27.9 ± 1.0 25 27.3 ± 1.5 15.3 ± 1.1 22.9 ± 1.2 50 12.4 ± 1.1 8.7 ± 1.2 9.41 ± 1.16 M A N U S C R I P T A C C E P T E D

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Free radicals or reactive oxygen species (ROS) are highly toxic and their damaging effects result in a variety of detrimental health issues such as neurodegenerative, cardiovascular and age-related diseases. Human body has evolved an effective defense system including superoxide dismutase (SOD) and catalase against the toxicity of these free radicals. SOD is a metalloenzyme and it acts as an excellent antioxidant to protect the body from superoxide radicals that are generated in the biological system. However, the clinical use of SOD is limited due to its short in vivo life span, and its large size that hampered its penetration across the cell membranes. Pharmaceuticals that provide ROS scavenging systems are the most effective when the production of ROS exceeds the scavenging capacity of endogenous SOD as a result of aging or pathological processes. Inspired by the Nature, scientists have designed metal-based mimics of the superoxide dismutase. This review focuses on different copper complexes that are developed from bioactive ligands and mimic the protecting action of the SOD.

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Promising cytotoxic gold(iii) complexes with general formula [Au{(1,2-DACH)}₂]Cl₃ are reported.