Synthesis and antiamoebic activity of new cyclooctadiene ruthenium(II) complexes with 2-acetylpyridine and benzimidazole derivatives

Reaction of [Ru(eta4-C8H12) (CH3CN)2 Cl2] with 2-(2-pyridyl) benzimidazole or Schiff bases derived from 2-acetylpyridine and S-methyldithiocarbazate, S-benzyldithiocarbazate and thiosemicarbazide leads to form new complexes of the type [Ru(eta4-C8H12)(L)Cl2] (where L=ligand). In vitro, most of the compounds exhibited potent activity and the Ru derivatives 1a [Ru(eta4-C8H12)(2-Acpy-SMDT)Cl2], 2a [Ru(eta4-C8H12)(2-Acpy-SBDT)Cl2] and 3a [Ru(eta4-CsH12)(2-Acpy-TSC)Cl2] were found more active than metronidazole against (HK-9) strain of Entamoeba histolytica.     

Synthesis,spectral studies and screening for amoebicidal activity of new palladium(II) complexes derived from thiophene-2-carboxaldehyde thiosemicarbazones

In view of the antiamoebic properties observed for many thiophene-2-carboxaldehyde thiosemicarbazones, a series of N(4)-substituted thiosemicarbazones metal complexes derived from thiophene-2-carboxaldehyde was prepared for evaluation against Entamoeba histolytica. Reaction of thiophene-2-carboxaldehyde with cycloalkylaminothiocarbonylhydrazines having different amines gave the corresponding thiosemicarbazones. Reaction of latter with [Pd(DMSO)(2)Cl(2)] gave requisite palladium thiosemicarbazone complexes of the type [Pd(TSC)Cl(2)] (where TSC=thiosemicarbazones). Screening of antiamoebic activity of these compounds was assayed in vitro against (HM-1:1MSS) strain of E. histolytica. Enhancement of antiamoebic resulted from introducing palladium metal in the thiosemicarbazone moiety. Among the studied compounds, [Pd(2-TCA-1,2,3,4-THQTSC)Cl(2)] (2a) showed better activity.     

Synthesis, spectral studies and in vitro assessment for antiamoebic activity of new cyclooctadiene ruthenium(II) complexes with 5-nitrothiophene-2-carboxaldehyde thiosemicarbazones

We report here the synthesis, characterization and in vitro antiamoebic activity of 5-nitrothiophene-2-carboxaldehyde thiosemicarbazones (TSC), 1–5, and their bidentate complexes [Ru(η⁴-C₈H₁₂)(TSC)Cl₂] 1a–5a. The biological studies of these compounds were investigated against HK-9 strain of Entamoeba histolytica and the concentration causing 50% cell growth inhibition (IC₅₀) was calculated in the micromolar range. The ligands exhibited antiamoebic activity in the range (2.05–5.29 μM). Screening results indicated that the potencies of the compounds increased by the incorporation of ruthenium(II) in the thiosemicarbazones. The complexes 1a–5a showed antiamoebic activity with an IC₅₀ of 0.61–1.43 μM and were better inhibitors of growth of E. histolytica, based on IC₅₀ values. The most promising among them is Ru(II) complex 2a having 1,2,3,4-tetrahydroquinoline as N⁴ substitution.     

New palladium(II) complexes of 5-nitrothiophene-2-carboxaldehyde thiosemicarbazones. synthesis,spectral studies and in vitro anti-amoebic activity

Thiosemicarbazones (1-7) and their palladium(II) complexes (1a-7a) of the type [Pd(TSCN)Cl(2)] (where TSCN=thiosemicarbazone) were prepared from 5-nitro thiophene-2-carboxaldehyde and [Pd(DMSO)(2)Cl(2)], respectively. Coordination via the thionic sulphur and the azomethine nitrogen atom of the thiosemicarbazones to the metal ion were confirmed by spectral data. These compounds were screened in vitro against (HK-9) strain of Entamoeba histolytica possess amoebicidal properties. Enhancement of antiamoebic activity resulted due to the introduction of palladium metal in the thiosemicarbazone moiety. The most promising of the group tested are [Pd(5-N-2-TCA-COTSCN)Cl(2)] and [Pd(5-N-2-TCA-AdmTSCN)Cl(2)] comparable to that of metronidazole.     

Coordination of Thiosemicarbazones and Bis(thiosemicarbazones) to Bismuth(III) as a Strategy for the Design of Metal-Based Antibacterial Agents

Complexes [Bi(2Fo4Ph)Cl(2) ] (1), [Bi(2Ac4Ph)Cl(2) ] (2), [Bi(2Bz4Ph)Cl(2) ] (3), [Bi(H(2) Gy3DH)Cl(3) ] (4), [Bi(H(2) Gy4Et)(OH)(2) Cl] (5), and [Bi(H(2) Gy4Ph)Cl(3) ] (6) were prepared with pyridine-2-carbaldehyde 4-phenylthiosemicarbazone (H2Fo4Ph), 1-(pyridin-2-yl)ethanone 4-phenylthiosemicarbazone (H2Ac4Ph), phenyl(pyridin-2-yl)methanone 4-phenylthiosemicarbazone (H2Bz4Ph), as well as with glyoxaldehyde bis(thiosemicarbazone) (H(2) Gy4DH) and its 4-Et (H(2) Gy4Et) and 4-Ph (H(2) Gy4Ph) derivatives. The complexes exhibited antibacterial activities against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, and Pseudomonas aeruginosa. Coordination to Bi(III) proved to be an effective strategy to increase the antibacterial activity of the thiosemicarbazones and bis(thiosemicarbazones).     

Synthesis, characterization and in vitro anti-amoebic activity of new palladium(II) complexes with 5-nitrothiophene-2-carboxaldehyde N(4)-substituted thiosemicarbazones

Reaction between [Pd(DMSO)(2)Cl(2)] (DMSO=dimethylsulfoxide) and N(4)-substituted thiosemicarbazones derived from 5-nitrothiophene-2-carboxaldehyde (L) afforded the complexes [Pd(L)Cl(2)]. These new complexes have been characterized by elemental analyses and spectroscopic studies. Spectroscopic studies reveal that thionic sulfur and azomethine nitrogen atom of thiosemicarbazones are coordinated to metal ion. The testing of the anti-amoebic activity of these complexes against the protozoan parasite Entamoeba histolytica suggests that compound 9, 10, and 11 might be endowed with important anti-amoebic properties since they showed less IC(50) values than metronidazole. Moreover, compound 11 displays notable amoebicidal activity than metronidazole (IC(50) values of 0.79 microM vs 1.93 microM, respectively).     

Half-sandwich Ru II[9]aneS3 complexes structurally similar to antitumor-active organometallic piano-stool compounds: preparation, structural characterization and in vitro cytotoxic activity

The preparation, structural characterization, and chemical behavior in aqueous solution of a series of new Ru[9]aneS3 half-sandwich complexes of the type [Ru([9]aneS3)Cl(NN)][CF3SO3] and [Ru([9]aneS3)(dmso-S)(N-N)][CF3SO3]2 (5-15, NN=substituted bpy or 2x1-methylimidazole) are described. The X-ray structures of [Ru([9]aneS3)Cl(3,3'-H2dcbpy)][CF3SO3] (9) (3,3'-H2dcbpy=3,3'-dicarboxy-2,2'-bipyridine), [Ru([9]aneS3)Cl(4,4'-dmobpy)][CF3SO3] (13) (4,4'-dmobpy=4,4'-dimethoxy-2,2'-bipyridine), and [Ru([9]aneS3)Cl(1-MeIm)2][CF3SO3] (15) (1-MeIm=1-methylimidazole) were also determined. The new compounds are structurally similar to anticancer-active organometallic half-sandwich complexes of formula [Ru(eta6-arene)Cl(NN)][PF6]. Three chloro compounds (5, 9, 15) were tested in vitro for cytotoxic activity against two human cancer cell lines in comparison with the previously described [Ru([9]aneS3)Cl(en)][CF3SO3] (1, en=ethylenediamine), [Ru([9]aneS3)Cl(bpy)][CF3SO3] (2), and with their common dmso precursor [Ru([9]aneS3)Cl(dmso-S)2][CF3SO3] (3). Only the ethylenediamine complex 1 showed some antiproliferative activity, ca. one order of magnitude lower than the reference organometallic half-sandwich compound RM175 that contains biphenyl instead of [9]aneS3. This compound was further tested against a panel of human cancer cell lines (including one resistant to cisplatin).     

Efficient photodynamic therapy of cancer using chemotherapeutic porphyrin-ruthenium metalla-cubes

Two cationic octanuclear metalla-cubes [Ru(8)(η(6)-C(6)H(5)Me)(8)(tpp-H2)(2)(dhbq)(4)](8+) and [Ru(8)(η(6)-p-iPrC(6)H(4)Me)(8)(tpp-H2)(2)(dhbq)(4)](8+) were prepared and evaluated as dual photosensitizers and chemotherapeutics in cancer cells. In the dark, the complexes presented high cytotoxicity towards only melanoma and ovarian cancer cells. However, the complexes exhibited good phototoxicities toward all cancer cells (1μM concentration, LD(50)=2-7J/cm(2)), thus suggesting a dual synergistic effect with good properties of both the arene ruthenium chemotherapeutics and the porphyrin photosensitizers.     

Highly cytotoxic trithiophenolatodiruthenium complexes of the type [(η6-p-MeC6H4Pr i )2Ru2(SC6H4-p-X)3]+: synthesis, molecular structure, electrochemistry, cytotoxicity, and glutathione oxidation potential

A series of cationic dinuclear p-cymene ruthenium trithiophenolato complexes of the type [(η(6)-p-MeC(6)H(4)Pr(i))(2)Ru(2)(SC(6)H(4)-p-X)(3)](+) (1 X is H, 2 X is Me, 3 X is Ph, 4 X is Br, 5 X is OH, 6 X is NO(2), 7 X is OMe, 8 X is CF(3), 9 X is F, 10 X is Pr(i), 11 X is Bu(t)) have been synthesized from the reaction of [(η(6)-p-MeC(6)H(4)Pr(i))RuCl(2)](2) with the corresponding thiol, isolated as the chloride salts, and further studied for their electrochemical properties, cytotoxicity towards human ovarian cancer cells, and catalytic activity for glutathione (GSH) oxidation. Complex 1 was also compared with the benzene and hexamethylbenzene analogues [(η(6)-C(6)H(6))(2)Ru(2)(SC(6)H(5))(3)](+) (12) and [(η(6)-C(6)Me(6))(2)Ru(2)(SC(6)H(5))(3)](+) (13). The most active compound [11]Cl was structurally studied by single-crystal X-ray diffraction analysis. The concentrations corresponding to 50 % inhibition of cancer cell growth (IC(50) values) in the A2780 and A2780cisR cell lines of these complexes except for 6 were in the submicromolar range, complex 11 showing an IC(50) value of 0.03 μM in both cell lines. The high in vitro anticancer activity of these complexes may be at least partially due to their catalytic potential for the oxidation of GSH, although there is no clear correlation between the IC(50) values and the turnover frequencies at about 50 % conversion. However, the cytotoxicity is tentatively correlated to the physicochemical properties of the compounds determined by the electronic influence of the substituents X (Hammett constants σ(p)) and the lipophilicity of the thiols p-XC(6)H(4)SH (calculated log P parameters).     

Synthesis and anti-amoebic activity of gold(I), ruthenium(II), and copper(II) complexes of metronidazole

A series of Au, Ru, and Cu complexes of metronidazole (= [1-(2-hydroxyethyl)-2-methyl-5-nitro-1H-imidazole; 1) were prepared as highly potent anti-amoebic drugs. The complexes [Au(PPh3)(1)]PF6 (2), [Ru(1)2(Cl)2(H2O)2] (3), and [Cu(1)2(mu-Cl)(H2O)]2Cl2 (4) were readily synthesized from [Au(PPh3)Cl], RuCl3 x 3 H2O, and CuCl2 x 2 H2O, respectively. All complexes were thoroughly characterized by IR, UV/VIS, 1H-NMR, FAB-MS, elemental and thermogravimetric analyses, and, in the case of 4, also by X-ray crystallography (Fig. 1). All complexes were evaluated in vitro as growth inhibitors of Entamoeba histolytica (HM1:IMSS strain). Their IC50 values were in the range of 0.10-0.51 microM (Table 2), which makes these drugs, especially the Cu(II) complex 4, considerably more potent than uncomplexed metronidazole (1; IC50 = 1.81 microM), the current standard drug for the worldwide treatment of amoebiasis.     

Novel ruthenium complex K2[Ru(dmgly)Cl4].2H2O is toxic to C6 astrocytoma cell line, but not to primary rat astrocytes

A novel class of ruthenium (III) complexes of formulas K[Ru(sar)2Cl2].12H2O and K2[Ru(dmgly)Cl4].2H2O, containing bidentate chelates N-methylglycine (sarcosine, sar) or N,N-dimethylglycine (dmgly) and additional chloro ligands were synthesized. The complexes have been obtained by direct reaction of ruthenium(III) chloride with corresponding bidentate ligand followed by addition of base (KOH). These new complexes were characterized by elemental analysis, IR and electronic absorption spectroscopy. As astrocytomas, the most common of all brain tumors, are still very difficult to treat, we examined the influence of newly synthesized ruthenium-based complexes, as well as the earlier synthesized analogue platinum(IV) complexes [Pt(dmgly)2Cl2], [Pt(sar)2Br2] and [Pt(dmgly)2Br2], on rat astrocytoma C6 cells in vitro. Among these complexes only K2[Ru(dmgly)Cl4].2H2O and [Pt(dmgly)2Br2] markedly inhibited the viability of non-confluent C6 cells. Furthermore, only complex K2[Ru(dmgly)Cl4].2H2O was able to reduce viability in confluent C6 cultures. Importantly, this complex was not toxic to primary rat astrocytes or macrophages. Having in mind that appropriate chemotherapy should be effective against tumor cells without harming normal tissues, complex K2[Ru(dmgly)Cl4].2H2O could be a promising agent for developing therapeutics against astrocytomas.     

Synthesis, characterization and DNA binding studies of two mixed ligand complexes of ruthenium(II)

Two mixed ligand complexes [Ru(bpy)(2)(DMHBT)]Cl(2)(1) and [Ru(phen)(2)(DMHBT)]Cl(2) (2) (where DMHBT is 11,13-dimethyl-13H-4,5,9,11,14-hexaaza-benzo[b]triphenylene-10,12-dione) have been synthesized and characterized by electrospray ionization (ESI) mass, (1)H-(1)H correlation spectroscopy (COSY), electronic spectroscopy, fluorescence spectroscopy and cyclic voltammetry. Spectroscopic titration and viscosity changes of calf thymus (CT)-DNA in the presence of incremental amount of complexes 1 and 2 clearly demonstrate that both these complexes bind intercalatively to DNA, with binding constant 2.87+/-0.20 x 10(4)M(-1) and 1.01+/-0.20 x 10(5)M(-1) for complexes 1 and 2, respectively. All the experimental evidences suggest that the ancillary ligand 2,2'-bipyridine (bpy) and 1,10-phenanthroline (phen) influences the intercalative binding of these complexes to DNA.     

Nitrate/nitrite reductase activity of sulfido/selenido bridged dinuclear ruthenium(III) complexes

Series of dinuclear species [Ru(2)(L)(2)(LH)(2)-mu-S(2)Cl(2)], [Ru(2)(L)(2)(LH)(4)-mu-Se(2)Cl(2)] (L=L(1)H and L(3)H) and [Ru(2)(L(2))(2)(L(2)H)-mu-Se(2)Cl(2)].2H(2)O, where L(1)H, L(2)H and L(3)H represent for 2-mercapto-5-phenyl-1,3,4-oxadiazole, 2-mercapto-benzimidazole and 2-mercapto-benzothiazole, respectively, have been prepared and characterized by their elemental analyses and spectral (IR, UV-visible, 1H NMR and FAB mass) data. The diamagnetism of these complexes are indicative of an exchange coupled dinuclear ruthenium(III) species containing S(2)(2-) and Se(2)(2-) bridges. The complexes along with free heterocycles (L(1)H-L(3)H) as well as RuCl(3) x 3H(2)0 were tested for their nitrate and nitrite reductase activities. The electrochemical behaviour of the complexes showed irreversible oxidation peaks at +(1.04-1.40) V quite comparable to those reported for sulphido bridged complexes.     

Structure-dependent in vitro cytotoxicity of the isomeric complexes [Ru(L)2Cl2] (L=o-tolylazopyridine and 4-methyl-2-phenylazopyridine) in comparison to [Ru(azpy)2Cl2]

The dichlorobis(2-phenylazopyridine)ruthenium(II) complexes, [Ru(azpy)(2)Cl(2)], are under renewed investigation due to their potential anticancer activity. The three most common isomers alpha-, beta- and gamma-[RuL(2)Cl(2)] with L= o-tolylazopyridine (tazpy) and 4-methyl-2-phenylazopyridine (mazpy) (alpha indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual cis, trans, cis positions, beta indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual cis, cis, cis positions, and gamma indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual trans, cis, cis positions) are synthesized and characterized by NMR spectroscopy. The molecular structures of gamma-[Ru(tazpy)(2)Cl(2)] and alpha-[Ru(mazpy)(2)Cl(2)] are determined by X-ray diffraction analysis. The IC(50) values of the geometrically isomeric [Ru(tazpy)(2)Cl(2)] and [Ru(mazpy)(2)Cl(2)] complexes compared with those of the parent [Ru(azpy)(2)Cl(2)] complexes are determined in a series of human tumour cell lines (MCF-7, EVSA-T, WIDR, IGROV, M19, A498 and H266). These data unambiguously show for all complexes the following trend: the alpha isomer shows a very high cytotoxicity, whereas the beta isomer is a factor 10 less cytotoxic. The gamma isomers of [Ru(tazpy)(2)Cl(2)] and [Ru(mazpy)(2)Cl(2)] display a very high cytotoxicity comparable to that of the gamma isomer of the parent compound [Ru(azpy)(2)Cl(2)] and to that of the alpha isomer. These biological data are of the utmost importance for a better understanding of the structure-activity relationships for the isomeric [RuL(2)Cl(2)] complexes.     

Optically active titanium complexes containing a tridentate linked amido-cyclopentadienyl ligand

Optically active titanium complexes Tieta5:eta1-C5R4SiMe2NC6H10 (OCH2Ph)-2Cl2 (R = H, Me), containing a cyclopentadienyl ligand linked to the chiral trans-2-benzyloxycyclohexylamido group, were synthesized and characterized in both enantiomerically pure forms. A single crystal X-ray structure analysis of (-)-(R, R)-Tieta5:eta1-C5H4SiMe2NC6H10(OCH2Ph)-2Cl2 shows a structure in which the benzyloxy group in the amido sidechain is not interacting with the titanium center. Upon activation with n-butyllithium, these complexes hydrogenate acetophenone N-benzylimine with low enantioselectivity.     

Third generation fluoroquinolones antibacterial drug based mixed-ligand Cu(II) complexes: structure,antibacterial activity,superoxide dismutase activity and DNA–interaction approach

The copper(II) complexes of the type [Cu(SPF)(Aⁿ)Cl]/[Cu(PFL)(Aⁿ)Cl] (where SPF is sparfloxacin, PFL is pefloxacin and Aⁿ is 2,2′-dipyridylamine/pyridine-2-carboxalehyde/thiophene-2-carboxaldehyde) were synthesised and were found to have a pyramidal geometry with a square base. The superoxide dismutase (SOD) like activity of the complexes were measured using an NBT/NADH/PMS system, these were expressed in terms of the concentration of complex which termianates the formation of formazan by 50% (IC₅₀ value) and found to range from 0.781 to 1.354 μM. The interactions of the complexes with DNA were studied by absorption titration, viscosity measurement and gel electrophoresis under physiological conditions. The antimicrobial efficiency of the complexes were tested on five different microorganisms and showed good biological activity.     

Metal–metal interactions in linear tri-, penta-, hepta-, and nona-nuclear ruthenium string complexes

Density functional theory (DFT) methodology was used to examine the structural properties of linear metal string complexes: [Ru(3)(dpa)(4)X(2)] (X = Cl(-), CN(-), NCS(-), dpa = dipyridylamine(-)), [Ru(5)(tpda)(4)Cl(2)], and hypothetical, not yet synthesized complexes [Ru(7)(tpta)(4)Cl(2)] and [Ru(9)(ppta)(4)Cl(2)] (tpda = tri-α-pyridyldiamine(2-), tpta = tetra-α-pyridyltriamine(3-), ppta = penta-α-pyridyltetraamine(4-)). Our specific focus was on the two longest structures and on comparison of the string complexes and unsupported ruthenium backboned chain complexes, which have weaker ruthenium-ruthenium interactions. The electronic structures were studied with the aid of visualized frontier molecular orbitals, and Bader's quantum theory of atoms in molecules (QTAIM) was used to study the interactions between ruthenium atoms. The electron density was found to be highest and distributed most evenly between the ruthenium atoms in the hypothetical [Ru(7)(tpta)(4)Cl(2)] and [Ru(9)(ppta)(4)Cl(2)] string complexes.     

Syntheses and DNA-binding studies of two ruthenium(II) complexes containing one ancillary ligand of bpy or phen: [Ru(bpy)(pp[2,3]p)2](ClO4)2 and [Ru(phen)(pp[2,3]p)2](ClO4)2

Two new ruthenium(II) complexes of [Ru(bpy)(pp[2,3]p)2](ClO4)2 and [Ru(phen)(pp[2,3]p)2](ClO4)(2) (bpy=2,2'-bipyridine, phen=1,10-phenanthroline, pp[2,3]p=pyrido[2',3':5,6]pyrazino[2,3-f][1,10]phenanthroline) have been synthesized and characterized by elemental analysis and 1H NMR spectra. The calf thymus DNA-binding properties of the two complexes were investigated by UV-visible and emission spectroscopy, competitive binding experiments with ethidium bromide and viscosity measurements. The results indicate that the two complexes intercalate between the base pairs of the DNA tightly with intrinsic DNA-binding constants of 3.08 x 10(6) and 6.53 x 10(6) M(-1) in buffered 50 mM NaCl, respectively, which are much larger than 6.9 x 10(5) M(-1) for [Ru(bpy)2(pp[2,3]p)](ClO4)2 containing two ancillary ligands of bpy.     

Synthesis, crystal structure, spectral properties and cytotoxic activity of platinum(II) complexes of 2-acetyl pyridine and pyridine-2-carbaldehyde N(4)-ethyl-thiosemicarbazones

The reactions of Na2PtCl4 with pyridine-2-carbaldehyde and 2-acetyl pyridine N(4)-ethyl-thiosemicarbazones, HFo4Et and HAc4Et respectively, afforded the complexes [Pt(Fo4Et)Cl], [Pt(HFo4Et)2]Cl2, [Pt(Fo4Et)2] and [Pt(Ac4Et)Cl], [Pt(HAc4Et)2]Cl2 x 2H2O, [Pt(Ac4Et)2]. The new complexes have been characterized by elemental analyses and spectroscopic studies. The crystal structure of the complex [Pt(Ac4Et)Cl] has been solved. The anion of Ac4E coordinates in a planar conformation to the central platinum(II) through the pyridyl N, azomethine N and thiolato S atoms. Intermolecular hydrogen, non-hydrogen bonds, pi-pi and weak Pt-pi contacts lead to aggregation and a supramolecular assembly. The cytotoxic activity for the platinum(II) complexes in comparison to that of cisplatin and thiosemicarbazones was evaluated in a pair of cisplatin-sensitive and -resistant ovarian cancer cell lines A2780 and A2780/Cp8. The platinum(II) complexes showed a cytotoxic potency in a very low micromolar range and were found able to overcome the cisplatin resistance of A2780/Cp8 cells.     

A novel phenotype-based approach for systematically screening antiproliferation metallodrugs

Ruthenium (Ru) derivatives have less toxicity and higher water-solubility than cisplatin, giving them great potential as antitumor metallodrugs. In this study, zebrafish were employed as a whole-organism model to screen new Ru compounds for anti-cell proliferation activity. After soaking fish embryos in cisplatin and five Ru derivatives, [Ru(terpy)(bpy)Cl]Cl, [Ru(terpy)(dppz)OH₂](ClO₄)₂, [Ru(terpy)(tMen)OH₂](ClO₄)₂, [Ru(terpy)(Me₄Phen)OH₂](ClO₄)₂, and Ru(bpy)₂Cl₂, only cisplatin and [Ru(terpy)(bpy)Cl]Cl-treated embryos displayed obvious phenotypic effects, such as fin-reduction. After further modification of [Ru(terpy)(bpy)Cl]Cl's main structure and the synthesis of two structurally related compounds, [Ru(terpy)(dcbpyH₂)Cl]Cl and [Ru(terpy)(dmbpy)Cl]Cl, only [Ru(terpy)(dmbpy)Cl]Cl exhibited fin-reduction phenotypes. TUNEL assays combined with immunostaining techniques revealed that treatment with cisplatin, [Ru(terpy)(bpy)Cl]Cl, and [Ru(terpy)(dmbpy)Cl]Cl led proliferating fin mesenchymal cells to undergo apoptosis and consequently caused fin-reduction phenotypes. Furthermore, [Ru(terpy)(bpy)Cl]Cl was able to activate the P53-dependent and independent pathways, and induced human hepatoma cells to undergo apoptosis. In summary, it was concluded that the zebrafish model was effective for the screening of phenotype-based antiproliferation metallodrugs.