Four structurally related Ru(II)-halide-PTA complexes, of general formula trans- or cis-[Ru(PTA)4X2] (PTA=1,3,5-triaza-7-phosphaadamantane, X=Cl (1, 2), Br (3, 4), were prepared and characterized. Whereas compounds 1 and 2 are known, the corresponding bromo derivatives 3 and 4 are new. The Ru(III)-PTA compound trans-[RuCl4(PTAH)2]Cl (5, PTAH=PTA protonated at one N atom), structurally similar to the well-known Ru(III) anticancer drug candidates (Na)trans-[RuCl4(ind)2] (NKP-1339, ind=indazole) and (Him)trans-[RuCl4(dmso-S)(im)] (NAMI-A, im=imidazole), was also prepared and similarly investigated. Notably, the presence of PTA confers to all complexes an appreciable solubility in aqueous solutions at physiological pH. The chemical behavior of compounds 1-5 in water and in physiological buffer, their interactions with two model proteins - cytochrome c and ribonuclease A - as well as with a single strand oligonucleotide (5'-CGCGCG-3'), and their in vitro cytotoxicity against a human colon cancer cell line (HCT-116) and a myeloid leukemia (FLG 29.1) were investigated. Upon dissolution in the buffer, sequential halide replacement by water molecules was observed for complexes 1-4, with relatively slow kinetics, whereas the Ru(III) complex 5 is more inert. All tested compounds manifested moderate antiproliferative properties, the cis compounds 2 and 4 being slightly more active than the trans ones (1 and 3). Mass spectrometry experiments evidenced that all complexes exhibit a far higher reactivity towards the reference oligonucleotide than towards model proteins. The chemical and biological profiles of compounds 1-5 are compared to those of established ruthenium drug candidates in clinical development.

Water-soluble Ru(II)- and Ru(III)-halide-PTA complexes (PTA = 1,3,5-triaza-7-phosphaadamantane): Chemical and biological properties / Battistin, F.; Scaletti, F.; Balducci, G.; Pillozzi, S.; Arcangeli, A.; Messori, L; Alessio, E.. - In: JOURNAL OF INORGANIC BIOCHEMISTRY. - ISSN 0162-0134. - ELETTRONICO. - 160:(2016), pp. 180-188. [10.1016/j.jinorgbio.2016.02.009]

Water-soluble Ru(II)- and Ru(III)-halide-PTA complexes (PTA = 1,3,5-triaza-7-phosphaadamantane): Chemical and biological properties

SCALETTI, FEDERICA;BALDUCCI, GIANNI;PILLOZZI, SERENA;ARCANGELI, ANNAROSA;MESSORI, LUIGI;ALESSIO, ENZO
2016

Abstract

Four structurally related Ru(II)-halide-PTA complexes, of general formula trans- or cis-[Ru(PTA)4X2] (PTA=1,3,5-triaza-7-phosphaadamantane, X=Cl (1, 2), Br (3, 4), were prepared and characterized. Whereas compounds 1 and 2 are known, the corresponding bromo derivatives 3 and 4 are new. The Ru(III)-PTA compound trans-[RuCl4(PTAH)2]Cl (5, PTAH=PTA protonated at one N atom), structurally similar to the well-known Ru(III) anticancer drug candidates (Na)trans-[RuCl4(ind)2] (NKP-1339, ind=indazole) and (Him)trans-[RuCl4(dmso-S)(im)] (NAMI-A, im=imidazole), was also prepared and similarly investigated. Notably, the presence of PTA confers to all complexes an appreciable solubility in aqueous solutions at physiological pH. The chemical behavior of compounds 1-5 in water and in physiological buffer, their interactions with two model proteins - cytochrome c and ribonuclease A - as well as with a single strand oligonucleotide (5'-CGCGCG-3'), and their in vitro cytotoxicity against a human colon cancer cell line (HCT-116) and a myeloid leukemia (FLG 29.1) were investigated. Upon dissolution in the buffer, sequential halide replacement by water molecules was observed for complexes 1-4, with relatively slow kinetics, whereas the Ru(III) complex 5 is more inert. All tested compounds manifested moderate antiproliferative properties, the cis compounds 2 and 4 being slightly more active than the trans ones (1 and 3). Mass spectrometry experiments evidenced that all complexes exhibit a far higher reactivity towards the reference oligonucleotide than towards model proteins. The chemical and biological profiles of compounds 1-5 are compared to those of established ruthenium drug candidates in clinical development.
2016
160
180
188
Goal 3: Good health and well-being
Battistin, F.; Scaletti, F.; Balducci, G.; Pillozzi, S.; Arcangeli, A.; Messori, L; Alessio, E.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1084939
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