Structurally Diverse Metal Coordination Compounds, Bearing Imidodiphosphinate and Diphosphinoamine Ligands, as Potential Inhibitors of the Platelet Activating Factor
Metal complexes bearing dichalcogenated imidodiphosphinate ligands (E = O, S, Se, Te), which act as (E,E) chelates, exhibit a remarkable variety of three-dimensional structures. A series of such complexes, namely, square-planar , tetrahedral , E = O, S, and octahedral , were tested as potential inhibitors of either the platelet activating factor (PAF)- or thrombin-induced aggregation in both washed rabbit platelets and rabbit platelet rich plasma. For comparison, square-planar , X = Cl, Br, the corresponding metal salts of all complexes and the ligand were also investigated. showed the highest anti-PAF activity but did not inhibit the thrombin-related pathway, whereas , with also a significant PAF inhibitory effect, exhibited the highest thrombin-related inhibition. and inhibited moderately both PAF and thrombin, being more effective towards PAF. This work shows that the PAF-inhibitory action depends on the structure of the complexes studied, with the bulkier being the most efficient and selective inhibitor. 1. Introduction Extensive research work over the last few years has revealed a remarkable structural variability of transition metal compounds bearing dichalcogenated imidodiphosphinate type of ligands, that is, , E = O, S, Se, Te; R, = various aryl or alkyl groups. These ligands have been shown to display great coordinating versatility, producing both single and multinuclear metal complexes, with a variety of bonding modes [1–3]. The coordinating flexibility of these (E,E) chelating ligands is attributed, mainly, to their large ( 4？？) E E？bite, which would accommodate a range of coordination sphere geometries. For instance, it was recently shown that the [ P(Se)NP(Se) ligand affords both tetrahedral and square-planar complexes of Ni(II) [4], in agreement with an earlier observation on the analogous [Ph2P(S)NP(S)Ph2 ligand [5]. Moreover, the nature of the R and peripheral groups of the [R2P(S)NP(S) ligand has been shown to affect the geometry of the complexes formed upon its coordination to Ni(II) [6, 7]. In a more general sense, depending on the nature of the metal ion, the chalcogen E atom and the R peripheral group, complexes bearing the above type of ligands were shown to contain rather diverse coordination spheres [8]. Such structural differences are of significant importance, as they are expected to lead not only to different stereochemical characteristics, but also to varied electronic properties of the metal site, which, in turn, could potentially result in significant biological reactivity [9]. The aim of this work was to investigate a
References
[1]
C. Silvestru and J. E. Drake, “Tetraorganodichalcogenoimidodiphosphorus acids and their main group metal derivatives,” Coordination Chemistry Reviews, vol. 223, no. 1, pp. 117–216, 2001.
[2]
I. Haiduc, “Dichalcogenoimidodiphosphinato ligands,” in Comprehensive Coordination Chemistry II: From Biology to Nanotechnology, vol. 1, pp. 323–347, Elsevier, Amsterdam, The Netherlands, 2003.
[3]
T. Chivers, J. Konu, J. S. Ritch, M. C. Copsey, D. J. Eisler, and H. M. Tuononen, “New tellurium-containing ring systems,” Journal of Organometallic Chemistry, vol. 692, no. 13, pp. 2658–2668, 2007.
[4]
N. Levesanos, S. D. Robertson, D. Maganas, C. P. Raptopoulou, A. Terzis, P. Kyritsis, and T. Chivers, “ complexes: stereoisomers ( ) and square-planar coordination ( ),” Inorganic Chemistry, vol. 47, no. 8, pp. 2949–2951, 2008.
[5]
E. Simón-Manso, M. Valderrama, and D. Boys, “Synthesis and single-crystal characterization of the square planar complex ,” Inorganic Chemistry, vol. 40, no. 14, pp. 3647–3649, 2001.
[6]
R. R？sler, C. Silvestru, G. Espinosa-Pérez, I. Haiduc, and R. Cea-Olivares, “Tetrahedral versus square-planar core in solid-state bis(dithioimidodiphosphinato)nickel(II) chelates. Crystal and molecular structures of ,” Inorganica Chimica Acta, vol. 241, no. 2, pp. 47–54, 1996.
[7]
D. Maganas, A. Grigoropoulos, and S. S. Staniland, “Tetrahedral and square-planar complexes, revisited: experimental and theoretical analysis of interconversion pathways, structural preferences and spin delocalization,” Inorganic Chemistry, vol. 49, no. 11, pp. 5079–5093, 2010.
[8]
T. Q. Ly and J. D. Woollins, “Bidentate organophosphorus ligands formed via P-N bond formation: synthesis and coordination chemistry,” Coordination Chemistry Reviews, vol. 176, no. 1, pp. 451–481, 1998.
[9]
E. I. Solomon, R. K. Szilagyi, S. DeBeer George, and L. Basumallick, “Electronic structures of metal sites in proteins and models: contributions to function in blue copper proteins,” Chemical Reviews, vol. 104, no. 2, pp. 419–458, 2004.
[10]
C. A. Demopoulos, R. N. Pinckard, and D. J. Hanahan, “Platelet-activating factor. Evidence for 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine as the active component (a new class of lipid chemical mediators),” Journal of Biological Chemistry, vol. 254, no. 19, pp. 9355–9358, 1979.
[11]
G. A. Zimmerman, T. M. McIntyre, S. M. Prescott, and D. M. Stafforini, “The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis,” Critical Care Medicine, vol. 30, no. 5, pp. S294–S301, 2002.
[12]
D. M. Stafforini, T. M. McIntyre, G. A. Zimmerman, and S. M. Prescott, “Platelet-activating factor, a pleiotrophic mediator of physiological and pathological processes,” Critical Reviews in Clinical Laboratory Sciences, vol. 40, no. 6, pp. 643–672, 2003.
[13]
G. Montrucchio, G. Alloatti, and G. Camussi, “Role of platelet-activating factor in cardiovascular pathophysiology,” Physiological Reviews, vol. 80, no. 4, pp. 1669–1699, 2000.
[14]
C. A. Demopoulos, H. C. Karantonis, and S. Antonopoulou, “Platelet activating factor—a molecular link between atherosclerosis theories,” European Journal of Lipid Science and Technology, vol. 105, no. 11, pp. 705–716, 2003.
[15]
J. M. López-Novoa, “Potential role of platelet activating factor in acute renal failure,” Kidney International, vol. 55, no. 5, pp. 1672–1682, 1999.
[16]
L. M. McManus and R. N. Pinckard, “PAF, a putative mediator of oral inflammation,” Critical Reviews in Oral Biology and Medicine, vol. 11, no. 2, pp. 240–258, 2000.
[17]
A. Kasperska-Zajac, Z. Brzoza, and B. Rogala, “Platelet-activating factor (PAF): a review of its role in asthma and clinical efficacy of PAF antagonists in the disease therapy,” Recent Patents on Inflammation and Allergy Drug Discovery, vol. 2, no. 1, pp. 72–76, 2008.
[18]
N. Nathan, Y. Denizot, M. C. Huc, C. Claverie, B. Laubie, J. Benveniste, and B. Arnoux, “Elevated levels of paf-acether in blood of patients with type 1 diabetes mellitus,” Diabete & Metabolisme, vol. 18, no. 1, pp. 59–62, 1992.
[19]
A. B. Tsoupras, C. Iatrou, C. Frangia, and C. A. Demopoulos, “The implication of platelet activating factor in cancer growth and metastasis: potent beneficial role of PAF-inhibitors and antioxidants,” Infectious Disorders—Drug Targets, vol. 9, no. 4, pp. 390–399, 2009.
[20]
A. B. Tsoupras, M. Chini, and M. Chini, “Anti-platelet-activating factor effects of highly active antiretroviral therapy (HAART): a new insight in the drug therapy of HIV infection?” AIDS Research and Human Retroviruses, vol. 24, no. 8, pp. 1079–1086, 2008.
[21]
J. M. Negro álvarez, J. C. Miralles López, J. L. Ortiz Martínez, A. Abellán Alemán A, and R. Rubio Del Barrio, “Platelet-activating factor antagonists,” Allergologia et Immunopathologia, vol. 25, no. 5, pp. 249–258, 1997.
[22]
S. Desquand, “Effects of PAF antagonists in experimental models—possible therapeutic implications,” Therapie, vol. 48, no. 6, pp. 585–597, 1993.
[23]
M. Koltai, D. Hosford, P. Guinot, A. Esanu, and P. Braquet, “Platelet activating factor (PAF). A review of its effects, antagonists and possible future clinical implications. I.,” Drugs, vol. 42, no. 1, pp. 9–29, 1991.
[24]
M. Koltai, D. Hosford, P. Guinot, A. Esanu, and P. Braquet, “PAF: a review of its effects, antagonists and possible future clinical implications. II.,” Drugs, vol. 42, no. 2, pp. 174–204, 1991.
[25]
C. X. Zhang and S. J. Lippard, “New metal complexes as potential therapeutics,” Current Opinion in Chemical Biology, vol. 7, no. 4, pp. 481–489, 2003.
[26]
S. H. van Rijt and P. J. Sadler, “Current applications and future potential for bioinorganic chemistry in the development of anticancer drugs,” Drug Discovery Today, vol. 14, pp. 1089–1197, 2009.
[27]
R. Timerbaev, “Advances in developing tris(8-quinolinolato)gallium(III) as an anticancer drug: critical appraisal and prospects,” Metallomics, vol. 1, pp. 193–198, 2009.
[28]
M. A. Jakupec and B. K. Keppler, “Gallium in cancer treatment,” Current Topics in Medicinal Chemistry, vol. 4, no. 15, pp. 1575–1583, 2004.
[29]
C. Marzano, M. Pellei, F. Tisato, and C. Santini, “Copper complexes as anticancer agents,” Anti-Cancer Agents in Medicinal Chemistry, vol. 9, no. 2, pp. 185–211, 2009.
[30]
Z. H. Chohan, “Metal-based antibacterial and antifungal sulfonamides: synthesis, characterization, and biological properties,” Transition Metal Chemistry, vol. 34, no. 2, pp. 153–161, 2009.
[31]
H. Sakurai, A. Katoh, and Y. Yoshikawa, “Chemistry and biochemistry of insulin-mimetic vanadium and zinc complexes. Trial for treatment of diabetes mellitus,” Bulletin of the Chemical Society of Japan, vol. 79, no. 11, pp. 1645–1664, 2006.
[32]
R. P. Kamalesh Babu, S. S. Krishnamurthy, and M. Nethaji, “Short-bite chiral diphosphazanes derived from (S)-α-methyl benzyl amine and their Pd, Pt and Rh metal complexes,” Tetrahedron Asymmetry, vol. 6, no. 2, pp. 427–438, 1995.
[33]
A. Silvestru, A. Rotar, J. E. Drake, et al., “Synthesis, spectroscopic characterization, and structural studies of new Cu(I) and Cu(II) complexes containing organophosphorus ligands, and crystal structures of , , , and ,” Canadian Journal of Chemistry, vol. 79, pp. 983–991, 2001.
[34]
A. Silvestru, D. Ban, and J. E. Drake, “Zinc(II) tetraorganodichalcogenoimidodiphosphinates. Crystal and molecular structure of ,” Revue Roumaine de Chimie, vol. 47, no. 10-11, pp. 1077–1084, 2002.
[35]
A. Davison and E. S. Switkes, “The stereochemistry of four-coordinate bis(imidodiphosphinato)metal(II) chelate complexes,” Inorganic Chemistry, vol. 10, no. 4, pp. 837–842, 1971.
[36]
V. García-Montalvo, R. Cea-Olivares, D. J. Williams, and G. Espinosa-Pérez, “Stereochemical consequences of the bismuth atom electron lone pair, a comparison between and systems. Crystal and molecular structures of tris[ -( , -diphenylphosphinoyl)- , -diphenylphosphinimidato]bismuth(III),[ , -indium(III), , and -gallium(III), ,” Inorganic Chemistry, vol. 35, no. 13, pp. 3948–3953, 1996.
[37]
G. C. Vougioukalakis, I. Stamatopoulos, and I. Stamatopoulos, “Controlled vinyl-type polymerization of norbornene with a nickel(II) diphosphinoamine/methylaluminoxane catalytic system,” Journal of Polymer Science A, vol. 47, no. 20, pp. 5241–5250, 2009.
[38]
F. T. Wang, J. Najdzionek, K. L. Leneker, H. Wasserman, and D. M. Braitsch, “Facile synthesis of imidotetraphenyldiphosphinic acids,” Synthesis and Reactivity in Inorganic and Metal-Organic Chemistry, vol. 8, pp. 119–125, 1978.
[39]
M. Lazanas, C. A. Demopoulos, S. Tournis, S. Koussissis, K. Labrakis-Lazanas, and X. Tsarouhas, “PAF of biological fluids in disease: I.V. Levels in blood in allergic reactions induced by drugs,” Archives of Dermatological Research, vol. 280, no. 2, pp. 124–126, 1988.
[40]
D. Tsoukatos, C. A. Demopoulos, A. D. Tselepis, M. C. Moschidis, A. Donos, A. Evangelou, and J. Benveniste, “Inhibition of cardiolipins of platelet-activating factor-induced rabbit platelet activation,” Lipids, vol. 28, no. 12, pp. 1119–1124, 1993.
[41]
H. Noth, “Crystal and molecular-structure of imido-tetraphenyl-dithio-phosphinic acid and imido-tetraphenyl-diphosphinic acid,” Zeitschrift für Naturforschung B, vol. 37, pp. 1491–1498, 1982.
[42]
A. I. Philippopoulos, N. Tsantila, C. A. Demopoulos, C. P. Raptopoulou, V. Likodimos, and P. Falaras, “Synthesis, characterization and crystal structure of the cis- complex with the bifunctional ligand (L) 2-( -pyridyl)quinoxaline. Biological activity towards PAF (Platelet Activating Factor) induced platelet aggregation,” Polyhedron, vol. 28, no. 15, pp. 3310–3316, 2009.
[43]
H. O. Heuer, “Involvement of platelet-activating factor (PAF) in septic shock and priming as indicated by the effect of hetrazepinoic PAF antagonists,” Lipids, vol. 26, no. 12, pp. 1369–1373, 1991.
[44]
J. R. Fletcher, A. G. DiSimone, and M. A. Earnest, “Platelet activating factor receptor antagonist improves survival and attenuates eicosanoid release in severe endotoxemia,” Annals of Surgery, vol. 211, no. 3, pp. 312–316, 1990.
[45]
I. Izquierdo, M. Merlos, and J. García-Rafanell, “Rupatadine: a new selective histamine H1 receptor and platelet-activating factor (PAF) antagonist. A review of pharmacological profile and clinical management of allergic rhinitis,” Drugs of Today, vol. 39, no. 6, pp. 451–468, 2003.
[46]
Y. Huo, J. Ekholm, and D. J. Hanahan, “A preferential inhibition by on platelet activating factor- and thrombin-induced serotonin secretion from washed rabbit platelets,” Archives of Biochemistry and Biophysics, vol. 260, no. 2, pp. 841–846, 1988.
[47]
I. B. Afanas'ev, E. A. Ostrakhovitch, E. V. Mikhal'chik, G. A. Ibragimova, and L. G. Korkina, “Enhancement of antioxidant and anti-inflammatory activities of bioflavonoid rutin by complexation with transition metals,” Biochemical Pharmacology, vol. 61, no. 6, pp. 677–684, 2001.
[48]
C. T. Dillon, T. W. Hambley, and T. W. Hambley, “Gastrointestinal toxicity, antiinflammatory activity, and superoxide dismutase activity of copper and zinc complexes of the antiinfiammatory drug indomethacin,” Chemical Research in Toxicology, vol. 16, no. 1, pp. 28–37, 2003.
[49]
D. Kovala-Demertzi, D. Hadjipavlou-Litina, M. Staninska, A. Primikiri, C. Kotoglou, and M. A. Demertzis, “Anti-oxidant, in vitro, in vivo anti-inflammatory activity and antiproliferative activity of mefenamic acid and its metal complexes with manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II),” Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 24, no. 3, pp. 742–752, 2009.
[50]
G. Mohan, R. Nagar, S. C. Agarwal, KM. A. Mehta, and C. S. Rao, “Syntheses and anti-inflammatory activity of diphenylamine-2, -dicarboxylic acid and its metal complexes,” Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 20, no. 1, pp. 55–60, 2005.
[51]
R. M. S. Pereira, N. E. D. Andrades, and N. E. D. Andrades, “Synthesis and characterization of a metal complex containing naringin and Cu, and its antioxidant, antimicrobial, antiinflammatory and tumor cell cytotoxicity,” Molecules, vol. 12, no. 7, pp. 1352–1366, 2007.
[52]
E. Pontiki, D. Hadjipavlou-Litina, and A. T. Chaviara, “Evaluation of anti-inflammatory and antioxidant activities of copper (II) Schiff mono-base and copper(II) Schiff base coordination compounds of dien with heterocyclic aldehydes and 2-amino-5-methyl-thiazole,” Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 23, no. 6, pp. 1011–1017, 2008.
[53]
V. O. Melnikova, K. Balasubramanian, and K. Balasubramanian, “Crosstalk between protease-activated receptor 1 and platelet-activating factor receptor regulates melanoma cell adhesion molecule (MCAM/MUC18) expression and melanoma metastasis,” Journal of Biological Chemistry, vol. 284, no. 42, pp. 28845–28855, 2009.
[54]
V. O. Melnikova and M. Bar-Eli, “Inflammation and melanoma metastasis,” Pigment Cell and Melanoma Research, vol. 22, no. 3, pp. 257–267, 2009.
