Exploring pta alternatives in the development of ruthenium–arene anticancer compounds

Organoruthenium pyrithione (1-hydroxypyridine-2-thione) complexes have been shown in our recent studies to be a promising family of compounds for development of new anticancer drugs. The complex [(n⁶-p-cymene)Ru(pyrithionato)(pta)]PF₆ contains phosphine ligand pta (1,3,5- triaza-7-phosphaadamantane) as a functionality that improves the stability of the complex and its aqueous solubility. Here, we report our efforts to find pta alternatives and discover new structural elements to improve the biological properties of ruthenium anticancer drugs. The pta ligand was replaced by a selection of phosphine, phosphite, and arsine ligands to identify new functionalities, leading to improvement in inhibitory potency towards enzyme glutathione S-transferase. In addition, cytotoxicity in breast, bone, and colon cancers was investigated.Centro de Química Inorgánic

Exploring pta alternatives in the development of ruthenium–arene anticancer compounds

Organoruthenium pyrithione (1-hydroxypyridine-2-thione) complexes have been shown in our recent studies to be a promising family of compounds for development of new anticancer drugs. The complex [(n⁶-p-cymene)Ru(pyrithionato)(pta)]PF₆ contains phosphine ligand pta (1,3,5- triaza-7-phosphaadamantane) as a functionality that improves the stability of the complex and its aqueous solubility. Here, we report our efforts to find pta alternatives and discover new structural elements to improve the biological properties of ruthenium anticancer drugs. The pta ligand was replaced by a selection of phosphine, phosphite, and arsine ligands to identify new functionalities, leading to improvement in inhibitory potency towards enzyme glutathione S-transferase. In addition, cytotoxicity in breast, bone, and colon cancers was investigated.Centro de Química Inorgánic

Sinteza železovih in bakrovih koordinacijskih spojin tiohidroksamskih kislin

Namen diplomske naloge je bil pripraviti železove in bakrove koordinacijske spojine tiohidroksamskih kislin ter njihova karakterizacija. V okviru diplomske naloge sem sintetiziral in optimiziral sintezo dveh tiohidroksamskih kislin, ter pripravil komplekse tudi s tremi drugimi kislinami. Sintetizirane tiohidroksamske kisline sem okarakteriziral z jedrsko magnetno resonanco (NMR), masno spektrometrijo in IR spektroskopijo. Pripravljene koodinacijske spojine pa sem okarakteriziral z masno spektrometrijo, elementno analizo CHN, ter IR in UV-Vis spektroskopijo.The purpose of my thesis was to prepare and characterize iron and copper coordination compounds of thiohydroxamic acids. Two thiohydroxamic acids were prepared and their synthesis protocols were optimized. Complexes of said acids and complexes with three other acids were prepared. The synthesized acids were characterized with nuclear magnetic resonance (NMR), mass spectrometry and IR spectroscopy. Prepared coordination compounds were characterized with mass spectrometry, elemental analysis CHN, IR and UV-Vis spectroscopy

Synthesis of 4-heteroaryl substituted pyrimidines and their coordination compounds

Sintetizirana je bila serija substituiranih pirimidinov iz acetil heteroaromatov, nato je bila izvedena metilacija pripravljenih spojin. Pri tem je prišlo do nastanka dveh različnih tipov produktov. Vse pripravljene spojine so bile uporabljene kot ligandi za sintezo renijevih koordinacijskih spojin. Vsi produkti so bili karakterizirani z jedrsko magnetno resonanco (NMR), masno spektrometrijo, IR spektroskopijo in elementno analizo CHN. Pripravljeni so bili tudi monokristali nekaterih spojin, katerim je bila določena struktura z rentgensko difrakcijo.A series of substituted pyrimidines were synthesized from acetyl substituted heteroaromatics. Methylation of the prepared compounds was then carried out and two different types of products were isolated. All the prepared compounds were used as ligands in the synthesis of rhenium coordination compounds. All products were characterized by nuclear magnetic resonance (NMR), mass spectrometry, IR spectroscopy and elemental analysis CHN. For some compounds, monocrystals were obtained and their molecular structures were determined by X-ray diffraction

Organometallic Ru(II), Rh(III) and Re(I) complexes of sterane-based bidentate ligands: Synthesis, solution speciation, interaction with biomolecules and anticancer activity

In this study, we present the synthesis, characterization and in vitro cytotoxicity of six organometallic [Ru(II)(η6-p-cymene)(N,N)Cl]Cl, [Rh(III)(η5-C5Me5)(N,N)Cl]Cl and [Re(I)(CO)3(N,N)Cl] complexes, in which the (N,N) ligands are sterane-based 2,2’-bipyridine derivatives (4-Me-bpy-St-OH,..

Organometallic Ru(II), Rh(III) and Re(I) complexes of sterane-based bidentate ligands : Synthesis, solution speciation, interaction with biomolecules and anticancer activity

In this study, we present the synthesis, characterization and in vitro cytotoxicity of six organometallic [Ru (II)(η6 -p-cymene)(N,N)Cl]Cl, [Rh(III)(η5 -C5Me5)(N,N)Cl]Cl and [Re(I)(CO)3(N,N)Cl] complexes, in which the (N,N) ligands are sterane-based 2,2’-bipyridine derivatives (4-Me-bpy-St-OH, 4-Ph-bpy-St-OH). The solution chemical behavior of the ligands and the complexes was explored by UV-visible spectrophotometry and 1 H NMR spectroscopy. The ligands and their Re(I) complexes are neutral at pH = 7.40; this contributes to their highly lipophilic character (log D7.40 > +3). The Ru(II) and Rh(III) half-sandwich complexes are much more hydrophilic, and this property is greatly affected by the actual chloride ion content of the medium. The half-sandwich Ru and Rh complexes are highly stable in 30% (v/v) DMSO/water (<5% dissociation at pH = 7.40); this is further increased in water. The Rh(III)(η5 -C5Me5) complexes were characterized by higher water/chloride exchange and pKa constants compared to their Ru(II)(η6 -p-cymene) counterparts. The Re(I)(CO)3 complexes are also stable in solution over a wide pH range (2–12) without the release of the bidentate ligand; only the chlorido co-ligand can be replaced with OH− at higher pH values. A comprehensive discussion of the binding affinity of the half-sandwich Ru(II) and Rh(III) complexes toward human serum albumin and calf-thymus DNA is also provided. The Ru(II)(η6 -p-cymene) complexes interact with human serum albumin via intermolecular forces, while for the Rh(III)(η5 -C5Me5) complexes the coordinative binding mode is suggested as well. They are also able to interact with calf-thymus DNA, most likely via the coordination of the guanine nitrogen. The Ru(II)(η6 -p-cymene) complexes were found to be the most promising among the tested compounds as they exhibited moderate-to-strong cytotoxic activity (IC50 = 3–11 µM) in LNCaP as well as in PC3 prostate cells in an androgen receptor-independent manner. They were also significantly cytotoxic in breast and colon adenocarcinoma cancer cell lines and showed good selectivity for cancer cells

Izstopajoče vedenje in pedagoški odzivi

Pomembno je, da se oblikuje takšna šolska klima, v kateri najde svoj "prostor pod soncem šole" vsak učenec, da vsak najde področje, kjer lahko participira, najde in vzdržuje smisel v prizadevanju za šolski uspeh, izkusi sprejetost, četudi je tako ali drugače "drugačen"