Andreia Almeida | Cardiff University (original) (raw)

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Papers by Andreia Almeida

Journal of Inorganic Biochemistry, 2014

Four different-anion Ag(I) compounds with the ligand norharmane (9H-Pyrido[3,4-b]indole; Hnor) an... more Four different-anion Ag(I) compounds with the ligand norharmane (9H-Pyrido[3,4-b]indole; Hnor) and having the general formula [Ag(Hnor)2](anion) (anion=ClO4(-), NO3(-) and BF4(-)) [Ag(Hnor)2(MeCN)](PF6) are reported, and studied in detail regarding their coordination mode and in vitro antiproliferative effects. X-ray structural analysis revealed that the complex with the PF6(-) anion has a MeCN solvent molecule weakly coordinated to Ag(I), making the metal coordination T-shaped, while the other compounds present the classical linear Ag(I) coordination. The compounds showed certain cell growth inhibitory effects in two different cancer cell lines, with the perchlorate containing complex being the most toxic and in fact comparable to cisplatin. Notably, the compounds are stable in visible light; and the luminescence in the solid state was found to be extremely weak, whereas in MeOH solution all compounds show a moderate to weak emission band at 375 nm, when excited at 290 nm.

Journal of inorganic biochemistry, Jan 18, 2015

Mercurial compounds are known to inhibit water permeation through aquaporins (AQPs). Although in ... more Mercurial compounds are known to inhibit water permeation through aquaporins (AQPs). Although in the last years some hypotheses were proposed, the exact mechanism of inhibition is still an open question and even less is known about the inhibition of the glycerol permeation through aquaglyceroporins. Molecular dynamics (MD) simulations of human aquaporin-3 (AQP3) have been performed up to 200ns in the presence of Hg(2+) ions. For the first time, we have observed the unbiased passage of a glycerol molecule from the extracellular to cytosolic side. Moreover, the presence of Hg(2+) ions covalently bound to Cys40 leads to a collapse of the aromatic/arginine selectivity filter (ar/R SF), blocking the passage of both glycerol and water. Interestingly, the local conformational changes of the protein follow mercury coordination by water and by aminoacidic donor atoms. Overall, the obtained results are important to improve the design of selective AQP inhibitors for future therapeutic and imag...

ABSTRACT In recent years, gold-based compounds have been proved to hold promise in chemical biolo... more ABSTRACT In recent years, gold-based compounds have been proved to hold promise in chemical biology being able to selectively inhibit proteins activities in cells and, therefore, to be exploited as either therapeutic agents or as chemical tools to detect protein/enzyme functions in living systems. In this area, we have recently described the properties of gold coordination complexes as potent and selective inhibitors of human aquaporins, protein channels involved in the transport of water and glycerol across biomembranes. Thus, we provide here an overview of the importance of aquaporins in various diseases and a detailed description of the state-of-the art progresses in the discovery of new inhibitors, including gold(III) complexes, and a description of their possible applications. Overall, the potential of coordination chemistry in providing compounds to modulate the activity of “elusive” drug targets, such as the aquaporins, will be discussed

Coordination Chemistry Reviews, 2013

Journal of Medicinal Chemistry, 2013

A series of gold(III) and palladium(II) heterometallic complexes with new iminophosphorane ligand... more A series of gold(III) and palladium(II) heterometallic complexes with new iminophosphorane ligands derived from ferrocenyl-phosphanes [{Cp-P(Ph 2 )=N-Ph} 2 Fe] (1), [{Cp-P(Ph 2 )=N-CH 2 -2-NC 5 H 4 } 2 Fe] (2) and [{Cp-P(Ph 2 )=N-CH 2 -2-NC 5 H 4 }Fe(Cp)] (3) have been synthesized and structurally characterized. Ligands 2 and 3 afford stable coordination complexes [AuCl 2 (3)]ClO 4 , [{AuCl 2 } 2 (2)](ClO 4 ) 2 , [PdCl 2 (3)] and [{PdCl 2 } 2 (2)]. The complexes have been evaluated for their antripoliferative properties in human ovarian cancer cells sensitive and resistant to cisplatin (A2780S/R), in human breast cancer cells (MCF7) and in a non-tumorigenic human embryonic kidney cell line (HEK-293T). The highly cytotoxic trimetallic derivatives M 2 Fe (M = Au, Pd) are more cytotoxic to cancer cells than their corresponding monometallic fragments. Moreover, these complexes were significantly more cytotoxic than cisplatin in the resistant A2780R and the MCF7 cell lines. Studies of the interactions of the trimetallic compounds with DNA and the zinc-finger protein PARP-1 indicate that they exert anticancer effects in vitro based on different mechanisms of actions with respect to cisplatin.

European Journal of Inorganic Chemistry, 2014

Journal of Inorganic Biochemistry, 2014

Four different-anion Ag(I) compounds with the ligand norharmane (9H-Pyrido[3,4-b]indole; Hnor) an... more Four different-anion Ag(I) compounds with the ligand norharmane (9H-Pyrido[3,4-b]indole; Hnor) and having the general formula [Ag(Hnor)2](anion) (anion=ClO4(-), NO3(-) and BF4(-)) [Ag(Hnor)2(MeCN)](PF6) are reported, and studied in detail regarding their coordination mode and in vitro antiproliferative effects. X-ray structural analysis revealed that the complex with the PF6(-) anion has a MeCN solvent molecule weakly coordinated to Ag(I), making the metal coordination T-shaped, while the other compounds present the classical linear Ag(I) coordination. The compounds showed certain cell growth inhibitory effects in two different cancer cell lines, with the perchlorate containing complex being the most toxic and in fact comparable to cisplatin. Notably, the compounds are stable in visible light; and the luminescence in the solid state was found to be extremely weak, whereas in MeOH solution all compounds show a moderate to weak emission band at 375 nm, when excited at 290 nm.

Journal of inorganic biochemistry, Jan 18, 2015

Mercurial compounds are known to inhibit water permeation through aquaporins (AQPs). Although in ... more Mercurial compounds are known to inhibit water permeation through aquaporins (AQPs). Although in the last years some hypotheses were proposed, the exact mechanism of inhibition is still an open question and even less is known about the inhibition of the glycerol permeation through aquaglyceroporins. Molecular dynamics (MD) simulations of human aquaporin-3 (AQP3) have been performed up to 200ns in the presence of Hg(2+) ions. For the first time, we have observed the unbiased passage of a glycerol molecule from the extracellular to cytosolic side. Moreover, the presence of Hg(2+) ions covalently bound to Cys40 leads to a collapse of the aromatic/arginine selectivity filter (ar/R SF), blocking the passage of both glycerol and water. Interestingly, the local conformational changes of the protein follow mercury coordination by water and by aminoacidic donor atoms. Overall, the obtained results are important to improve the design of selective AQP inhibitors for future therapeutic and imag...

ABSTRACT In recent years, gold-based compounds have been proved to hold promise in chemical biolo... more ABSTRACT In recent years, gold-based compounds have been proved to hold promise in chemical biology being able to selectively inhibit proteins activities in cells and, therefore, to be exploited as either therapeutic agents or as chemical tools to detect protein/enzyme functions in living systems. In this area, we have recently described the properties of gold coordination complexes as potent and selective inhibitors of human aquaporins, protein channels involved in the transport of water and glycerol across biomembranes. Thus, we provide here an overview of the importance of aquaporins in various diseases and a detailed description of the state-of-the art progresses in the discovery of new inhibitors, including gold(III) complexes, and a description of their possible applications. Overall, the potential of coordination chemistry in providing compounds to modulate the activity of “elusive” drug targets, such as the aquaporins, will be discussed

Coordination Chemistry Reviews, 2013

Journal of Medicinal Chemistry, 2013

A series of gold(III) and palladium(II) heterometallic complexes with new iminophosphorane ligand... more A series of gold(III) and palladium(II) heterometallic complexes with new iminophosphorane ligands derived from ferrocenyl-phosphanes [{Cp-P(Ph 2 )=N-Ph} 2 Fe] (1), [{Cp-P(Ph 2 )=N-CH 2 -2-NC 5 H 4 } 2 Fe] (2) and [{Cp-P(Ph 2 )=N-CH 2 -2-NC 5 H 4 }Fe(Cp)] (3) have been synthesized and structurally characterized. Ligands 2 and 3 afford stable coordination complexes [AuCl 2 (3)]ClO 4 , [{AuCl 2 } 2 (2)](ClO 4 ) 2 , [PdCl 2 (3)] and [{PdCl 2 } 2 (2)]. The complexes have been evaluated for their antripoliferative properties in human ovarian cancer cells sensitive and resistant to cisplatin (A2780S/R), in human breast cancer cells (MCF7) and in a non-tumorigenic human embryonic kidney cell line (HEK-293T). The highly cytotoxic trimetallic derivatives M 2 Fe (M = Au, Pd) are more cytotoxic to cancer cells than their corresponding monometallic fragments. Moreover, these complexes were significantly more cytotoxic than cisplatin in the resistant A2780R and the MCF7 cell lines. Studies of the interactions of the trimetallic compounds with DNA and the zinc-finger protein PARP-1 indicate that they exert anticancer effects in vitro based on different mechanisms of actions with respect to cisplatin.

European Journal of Inorganic Chemistry, 2014