Cisplatin analogues. cis-Dichloroaminoacid-tert-butylamineplatinum(II) complexes and their adducts with guanosine

A series of compounds of formula cis-[PtCl₂- (aaH)(tba)] (1) (aaH, N-coordinate amino acid; tba, tert-butylamine) were synthesized. The circular dichroism spectra of these compounds show that the phenylalanine and proline derivatives have an anomalous conformation in water solution. By reaction with guanosine (guo) compounds 1 give cis- [Pt(aaH)(tba)(guo)₂]Cl₂ (2), in which infrared and nuclear magnetic resonance evidence suggest N(7) coordination of guo. NMR and circular dichroism data suggest that in 2 the two guanosine ligands are arranged head-to-head and form a right-hand helix. The bulkiness of the other ligands make rotation around the PtN(7) bonds a slow process on the NMR time scale. The chiroptical properties of 2 are not greatly influenced by the absolute configuration of the amino acid, the right-hand screw probably arising by some guo-guo interaction since the derivatives of 9-methylguanine with chiral amino acids do not possess this conformation.Preliminary results on the reaction between 1 and calf thymus DNA are also briefly reported. They show that the interaction of 1 with DNA is of a lower extent than in the case of cisplatin and its diamine analogues, and that it is independent on the configuration of the amino acids.All these results are briefly discussed and tentatively correlated with the low antitumor activity of 1 reported in a previous paper.     

Study of the synthesis, antiproliferative properties, and interaction with DNA and polynucleotides of cisplatin-like Pt(II) complexes containing carcinogenic polyaromatic amines

The chemical and biological features of two newly synthesized [PtCl₂(L)(2-aminonaphthalene)] complexes (L is NH₃ or 2-aminonaphthalene) were compared with those of two already reported enantiomeric complexes of formula [PtCl₂(DABN)] [DABN is (R)-1,1′-binaphthyl-2,2′-diamine or (S)-1,1′-binaphthyl-2,2′-diamine]. Solution behavior, lipophilicity, cytotoxicity with regard to one colorectal (HCT116) and two ovarian (A2780 and A2780Cp8) human carcinoma cell lines, and in vitro DNA- and G-quadruplex-binding properties were evaluated. In particular, the cytotoxicity of [PtCl₂(NH₃)(2-aminonaphthalene)] was better than that of cisplatin for all cell lines, and rather resembled that of oxaliplatin. The solution behavior of the whole series of complexes and the absence of an evident relationship between lipophilicity and cytotoxicity seem to suggest that all these experimental parameters are probably smoothed out during the 3-day cytotoxicity experiments and do not strongly affect the half-maximal inhibitory concentrations. The results of electrophoretic studies indicate that different kinds of interaction with DNA can be involved in the mode of action of these complexes, with intercalation in double-stranded DNA and stacking on G-quadruplex DNA being strongly implicated in particular for [PtCl₂(NH₃)(2-aminonaphthalene)].     

Steric control of DNA interstrand cross-link sites of <Emphasis Type="Italic">trans</Emphasis> platinum complexes: specificity can be dictated by planar nonleaving groups

trans -dichloroplatinum(II) complexes exhibit antitumor activity violate the classical structure-activity relationships of platinum(II) complexes. These novel “nonclassical”trans platinum complexes also comprise those containing planar aromatic amines. Initial studies have shown that these compounds form a considerable amount of DNA interstrand cross-links (up to ∼30%) with a rate markedly higher than clinically ineffective transplatin. The present work has shown, using Maxam-Gilbert footprinting, that trans-[PtCl₂(NH₃)(quinoline)] and trans-[PtCl₂(NH₃)(thiazole)], representatives of the group of new antitumor trans-dichloroplatinum complexes containing planar amines, preferentially form DNA interstrand cross-links between guanine residues at the 5′-GC-3′ sites. Thus, DNA interstrand cross-linking by trans-[PtCl₂(NH₃)(quinoline)] and trans-[PtCl₂(NH₃)(thiazole)] is formally equivalent to that by antitumor cisplatin, but different from clinically ineffective transplatin which preferentially forms these adducts between complementary guanine and cytosine residues. This result shows for the first time that simple chemical modification of the structure of an inactive compound alters its DNA binding site into a DNA adduct of an active drug. Received: 6 January 2000 / Accepted: 8 March 2000     

Novel trans-platinum complexes of the histone deacetylase inhibitor valproic acid; synthesis, in vitro cytotoxicity and mutagenicity

The first examples of Pt complexes of the well known anti-epilepsy drug and histone deacetylase inhibitor, valproic acid (VPA), are reported. Reaction of the Pt(II) am(m)ine precursors trans-[PtCl₂(NH₃)(py)] and trans-[PtCl₂(py)₂] with silver nitrate and subsequently sodium valproate gave trans-[Pt(VPA_−1H)₂(NH₃)(py)] and trans-[Pt(VPA_−1H)₂(py)₂], respectively. The valproato ligands in both complexes are bound to the Pt(II) centres via the carboxylato functionality and in a monodentate manner. The X-ray crystal structure of trans-[Pt(VPA_−1H)₂(NH₃)(py)] is described. Replacement of the dichlorido ligands in trans-[PtCl₂(py)₂] and trans-[PtCl₂(NH₃)(py)] by valproato ligands (VPA_−1H) to yield trans-[Pt(VPA_−1H)₂(py)₂] and trans-[Pt(VPA_−1H)₂(NH₃)(py)] respectively, significantly enhanced cytotoxicity against A2780 (parental) and A2780 cisR (cisplatin resistant) ovarian cancer cells. The mutagenicity of trans-[Pt(VPA_−1H)₂(NH₃)(py)] and trans-[Pt(VPA_−1H)₂(py)₂] was determined using the Ames test and is also reported.     

Cytotoxicity, mutagenicity, cellular uptake, DNA and glutathione interactions of lipophilic trans-platinum complexes tethered to 1-adamantylamine

Cytotoxicity and mutagenicity of trans,trans,trans-[PtCl₂(CH₃COO)₂(NH₃)(1-adamantylamine)] [trans-adamplatin(IV)] and its reduced analog trans-[PtCl₂(NH₃)(1-adamantylamine)] [trans-adamplatin(II)] were examined. In addition, the several factors underlying biological effects of these trans-platinum compounds using various biochemical methods were investigated. A notable feature of the growth inhibition studies was the remarkable circumvention of both acquired and intrinsic cisplatin resistance by the two lipophilic trans-compounds. Interestingly, trans-adamplatin(IV) was considerably less mutagenic than cisplatin. Consistent with the lipophilic character of trans-adamplatin complexes, their total accumulation in A2780 cells was considerably greater than that of cisplatin. The results also demonstrate that trans-adamplatin(II) exhibits DNA binding mode markedly different from that of ineffective transplatin. In addition, the reduced deactivation of trans-adamplatin(II) by glutathione seems to be an important determinant of the cytotoxic effects of the complexes tested in the present work. The factors associated with cytotoxic and mutagenic effects of trans-adamplatin complexes in tumor cell lines examined in the present work are likely to play a significant role in the overall antitumor activity of these complexes.     

Synthesis, characterization, and cytotoxicities of platinum(II) complexes bearing pyridinecarboxaldimines containing bulky aromatic groups

Condensation of 2-pyridinecarboxaldehyde with several primary amines containing bulky aryl groups gave the corresponding pyridinecarboxaldimines (N-N′). Addition of these ligands to [PtCl₂(coe)]₂ (coe = cis-cyclooctene) gave complexes of the type cis-PtCl₂(N-N′) in moderate yields. The platinum complexes have been examined for their potential cytotoxicities against OV2008 (human ovarian carcinoma) and the analogous cisplatin-resistant cell line C13.     

Synthesis, structural characterisation and biological studies of new mononuclear platinum(II) complexes with sterically hindered heterocyclic ligands

Three novel cisplatin analogues were synthesized, designed according to an approach which violates the “classical” structure-activity relationship, by replacing the diamine ligands with a planar N donor heterocycle giving a sterically hindered complex. Moreover, the sterical hindrance of antitumor drug candidates potentially makes them less susceptible to deactivation by sulphur-containing proteins and helping to overcome resistance mechanisms. The resulting mononuclear complexes of sterically hindered polidentate heterocyclic N ligands [PtCl(bbp)]Cl (1) [bbp = 2,6-bis(2-benzimidazolyl)pyridine], [PtCl₂(dptdn)](H₂O) (2) [dptdn = sodium 5,6-diphenyl-3-(2′-pyridyl)-1,2,4-triazine-4″,4″′-disulfonate] and [(dptdn)(dpt)Pt]Cl₂(H₂O) (3) [dpt = 5,6-diphenyl-3-(2′-pyridyl)-1,2,4-triazine] have been prepared and structurally characterised. Both neutral and ionic complexes are present, with monofunctional (1) and bifunctional Pt(II) moieties (2) and coordinatively saturated Pt(II) ions in the mixed ligand complex (3), whose size and shape enable them to behave as novel scaffolds for DNA binding. All complexes were tested “in vitro” for their biological activity on human HT29 colorectal carcinoma and HepG2 hepatoma cells. The complexes (1) and (3), endowed with a positive charge, showed a potent cytotoxic activity and reduced cell viability with an efficacy higher than that of cisplatin; whilst the neutral bifunctional compound (2) was inactive. IC50 values have been calculated for the active compounds. The cytotoxic effects were confirmed by the accumulation of treated cells in subG0/G1 phase of cell cycle, by the loss of mitochondrial potential (Δψ_m) and by the chromatin condensation or fragmentation observed by means of fluorescence microscopy after Hoechst 33258 nuclear staining. A study on intracellular platinum uptake in HT29 cell line has been also performed and data obtained strongly suggest that the cytotoxicity of new tested complexes reported in this work is based on a different pharmacodynamic pattern with respect to cisplatin.     

Synthesis,characterization, and biological activity of platinum II,III, and IV pivaloamidine complexes

Imino ligands have proven to be able to activate the trans geometry of platinum(II) complexes towards antitumor activity. These ligands, like aromatic N-donor heterocycles, have a planar shape but, different from the latter, have still an H atom on the coordinating nitrogen which can be involved in H-bond formation. Three classes of imino ligands have been extensively investigated: iminoethers (HN=C(R)OR′), ketimines (HN=CRR′), and amidines (HN=C(R)NR′R″). The promising efficacy of the platinum compounds with amidines (activity comparable to that of cisplatin for cis complexes and much greater than that of transplatin for trans complexes) prompted us to extend the investigation to amidine complexes with a bulkier organic residue (R = t-Bu). The tert-butyl group can confer greater affinity for lipophilic environments, thus potentiating the cellular uptake of the compound. In the present study we describe the synthesis and characterization of pivaloamidine complexes of platinum(II), (cis and trans-[PtCl₂(NH₃){Z-HN=C(t-Bu)NH₂}] and cis and trans-[PtCl₂{Z-HN=C(t-Bu)NH₂}₂]), platinum(III) ([Pt₂Cl₄{HN=C(t-Bu)NH}₂(NH₃)₂]), and platinum(IV) (trans-[PtCl₄(NH₃){Z-HN=C(t-Bu)NH₂}] and trans-[PtCl₄{Z-HN=C(t-Bu)NH₂}₂]). The cytotoxicity of all new Pt complexes was tested toward a panel of cultured cancer cell lines, including cisplatin and multidrug resistant variants. In addition, cellular uptake and DNA binding, perturbations of cell cycle progression, induction of apoptosis, and p53 activation were investigated for the most promising compound trans-[PtCl₂(NH₃){Z-HN=C(t-Bu)NH₂}]. Remarkably, the latter complex was able to overcome both acquired and intrinsic cisplatin resistance.     

3,5-diacetyl-1,2,4-triazol bis(4N-substituted thiosemicarbazone) palladium(II) complexes: synthesis, structure, antiproliferative activity and low toxicity on normal kidney cells

Treatment of ⁴N-monosubstituted bis(thiosemicarbazone) ligands of 3,5-diacetyl-1,2,4-triazol series with lithium tetrachloridopalladate gave the dinuclear complexes of general formula [Pd(μ-H₃L^1-5)]₂, but using dichloridobistriphenylphosphinepalladium(II) salt, the first mononuclear bis(thiosemicarbazone)-palladium-triphenylphosphine complexes of the 3,5-diacetyl-1,2,4-triazol series, [Pd(H₃L^1-5)PPh₃], have been obtained. All the compounds have been characterized by elemental analysis and by IR and NMR spectroscopy, and the crystal and molecular structures of dinuclear complexes [Pd(μ-H₃L³)]₂ and [Pd(μ-H₃L⁵)]₂ as well as mononuclear complexes [Pd(H₃L¹)PPh₃], [Pd(H₃L²)PPh₃], [Pd(H₃L³)PPh₃] and [Pd(H₃L⁴)PPh₃] have been determined by X-ray crystallography. The new compounds synthesized have been evaluated for antiproliferative activity in vitro against NCI-H460, A2780 and A2780cisR human cancer cell lines. Subsequent toxicity study, on normal renal LLC-PK1 cells, shows that all compounds investigated exhibit very low toxicity on kidney cells with respect to cisplatin.     

Novel C,N-chelate platinum(II) antitumor complexes bearing a lipophilic ethisterone pendant

The novel steroidal carrier ligand 17-α-[4′-ethynyl-dimethylbenzylamine]-17-β-testosterone (ET-dmba 1) and the steroid — C,N-chelate platinum(II) derivatives [Pt(ET-dmba)Cl(L)] (L = DMSO (2) and PTA (3; PTA = 1,3,5-triaza-7-phosphaadamantane)) have been prepared. Values of IC₅₀ were calculated for the new platinum complexes 2 and 3 against a panel of human tumor cell lines representative of ovarian (A2780 and A2780cisR) and breast cancers (T47D). At 48 h incubation time complexes 2 and 3 show very low resistance factors (RF of < 2) against an A2780 cell line which has acquired resistant to cisplatin and were more active than cisplatin (about 4-fold for 3) in T47D (AR+, AR = androgen receptor). Compound 1 retains a moderate degree of relative binding affinity (RBA = 0.94%) for androgen receptors. The cytotoxicity of the non steroidal platinum analogues [Pt(dmba)Cl(L)] (dmba = dimethylbenzylamine; L = DMSO (4) and PTA (5)) has also been studied for comparison purposes. Theoretical calculations at the BP86/def2-TZVP level of theory on complex 3 have been undertaken.     

Ruthenium(II) carbonyl complexes containing S-methylisothiosemicarbazone based tetradentate ligand: synthesis, characterization and biological applications

A series of hexa-coordinated ruthenium(II) complexes of the type [Ru(CO)(B)L ⁿ ] (n = 1–4; B = PPh₃, AsPh₃ or Py) have been synthesized by reacting dibasic quadridentate Schiff base ligands H₂L ⁿ (n = 1–4) with starting complexes [RuHCl(CO)(EPh₃)₂(B)] (E = P or As; B = PPh₃, AsPh₃ or Py). The synthesized complexes were characterized using elemental and various spectral studies including UV–Vis, FT-IR, NMR (¹H, ¹³C and ³¹P) and mass spectroscopy. An octahedral geometry was tentatively proposed for all the complexes based on the spectral data obtained. The experiments on antioxidant activity showed that the ruthenium(II) S-methylisothiosemicarbazone Schiff base complexes exhibited good scavenging activity against various free radicals (DPPH, OH and NO). The in vitro cytotoxicity of these complexes has been evaluated by MTT assay. The results demonstrate that the complexes have good anticancer activities against selected cancer cell line, human breast cancer cell line (MCF-7) and human skin carcinoma cell line (A431). The DNA cleavage studies showed that the complexes have better cleavage of pBR 322 DNA.     

Synthesis, spectroscopical characterization and the biological activity in vitro of new platinum(II) complexes with imidazo[1,5-a]-1,3,5-triazine derivatives and dimethylsulfoxide

A series of platinum(II) complexes with 6,8-dimethylimidazo[1,5-a]-1,3,5-triazin-4(3H)-one (6,8-DiMe-4-O-IMT) (I) and 6,8-dimethyl-2-thioxo-2,3-dihydroimidazo[1,5-a]-1,3,5-triazin-4(1H)-one (6,8-DiMe-4-O-2-S-IMT) (II) of formula trans-[PtCl₂(dmso)(6,8-DiMe-4-O-IMT)] (1a) and trans-[PtCl₂(dmso)(6,8-DiMe-4-O-2-S-IMT)] (2a) have been prepared and characterized with ¹H, ¹³C, ¹⁵N, ¹⁹⁵Pt NMR and IR. Significant ¹⁵N NMR upfield coordination shifts (81-96 ppm) of N(7) atom indicate this nitrogen atom as a coordination site. The multinuclear NMR and IR spectra indicate the square planar geometry with N(7) bonded heterocycles, S-bonded dimethylsulfoxide and two trans chloride anions. The platinum(II) complexes were tested for their antiproliferative activity in vitro against the cells of four human cell lines: SW707 rectal adenocarcinoma, A549 non-small cell lung carcinoma, T47D breast cancer and HCV29T bladder cancer. The activity of (1a, 2a) was lower than that of cisplatin.     

Methimazole complexes of platinum(II): Synthesis, characterization and redox behavior

A variety of platinum(II) complexes of methimazole (2-mercapto-1-methylimidazole; HImS = neutral form and ImS = thiolate form), coordinated in both thione and thiolate forms, have been isolated by reacting methimazole with [PtCl(terpy)]Cl (terpy = 2,2′:6′,2″ terpyridine), [PtCl₂(bipy)] (bipy = bipyridine), [PtCl₂(o-phen)] (o-phen = o-phenanthroline), [PtCl₂(CH₃CN)₂] and [PtCl₂(COD)] (COD = 1,5-cyclooctadiene). These complexes were characterized by electronic absorption, IR and NMR (¹H, ¹³C, ¹⁹⁵Pt) spectroscopies. Molecular structure of [Pt(bipy)(HImS)₂]Cl₂·3H₂O (3a·3H₂O) has been established by single crystal X-ray crystallography. Platinum thiolate complex, [Pt(ImS)₂(HImS)₂] (5), could be obtained by treatment of [Pt(HImS)₄]Cl₂ with sodium methoxide in methanol. The solution of 5 in organic solvents yielded bi- and tri-nuclear platinum complexes. The effect of diimine ligands on oxidation of methimazole moiety in the complexes has been studied by electrochemical oxidation and pulse radiolytic oxidation employing specific one-electron oxidant, radical.     

Platinum group metal complexes of bis(2-(diphenylphosphino)ethyl benzylamine and bis(2-(diphenylarsino)ethyl)benzylamine

Rh(I), Ir(I), Pd(II) and Pt(II) metal complexes of bis(2-diphenylphosphino)ethyl)benzylamine(DPBA) and bis(2-diphenylarsino)ethyl)benzylamine (DABA) have been synthesized using various starting materials. Reaction of RhCl(CO)(AsPh₃)₂ with DPBA or DABA in methanol resulted in the formation of cationic complexes of the composition, [Rh(CO)(L)]Cl (L = DPBA or DABA). Interaction of [IrCl(COD)]₂ with DPBA in benzene resulted in the formation of a neutral complex [IrCl(DPBA)]. Reaction of [PdCl₂(COD)] with the ligand DPBA in benzene resulted in a cationic complex of the composition [PdCl(DPBA)]Cl. Interaction of [PdCl(DPBA)]BPh₄ with SnCl₂ gave the complex [Pd(SnCl₃)(DPBA)]BPh₄. The ligands DPBA and DABA react with PtCl₂(COD) in acetone to give neutral, Pt(II) complexes of the type, [PtCl₂L] (L = DPBA or DABA). All the complexes were fully characterized by elemental analysis, conductivity measurements, IR and far-IR and ³¹P{¹H} NMR spectral data.     

Structural characterization and DNA interactions of new cytotoxic transplatin analogues containing one planar and one nonplanar heterocyclic amine ligand

trans-Diaminedicholoroplatinum(II) complexes with one planar and one non-planar heterocyclic amine ligand were designed as new potential antitumor drugs. The X-ray crystallographic structures of trans-[PtCl₂(4-picoline)(piperidine)] and trans-[PtCl₂(4-picoline)(piperazine)]·HCl revealed that the piperidine and piperazine ligands bind to the platinum through the equatorial position and that the ligands adopt the chair conformation. The nonplatinated amine of the piperazine can form hydrogen bonds with atoms that are approximately 7.5 Å away from the Pt binding site. DNA is considered a major pharmacological target of platinum compounds. Hence, to expand the database correlating structural features of platinum compounds and DNA distortions induced by these compounds, which may facilitate identification of more effective anticancer platinum drugs, we describe the DNA binding mode in a cell-free medium of trans-[PtCl₂(4-picoline)(piperidine)] and trans-[PtCl₂(4-picoline)(piperazine)]·HCl. Interestingly, the overall impact of the replacement of the second ammine group in transplatin by the heterocyclic ligands appears to change the character of the global conformational changes induced in DNA towards that induced by cisplatin. The clinical ineffectiveness of the parent transplatin has been proposed to be also associated with its reduced capability to form bifunctional adducts in double-helical DNA. The results of the present work support the view that replacement of both ammine groups of transplatin by heterocyclic ligands enhances cytotoxicity probably due to the marked enhancement of the stability of intrastrand cross-links in double-helical DNA.     

Design of vanadium mixed-ligand complexes as potential anti-protozoa agents

In the search for new therapeutic tools against Chagas’ disease (American Trypanosomiasis) four novel mixed-ligand vanadyl complexes, [V^IVO(L²-2H)(L¹)], including a bidentate polypyridyl DNA intercalator (L¹) and a tridentate salycylaldehyde semicarbazone derivative (L²) as ligands were synthesized, characterized by a combination of techniques, and in vitro evaluated. EPR suggest a distorted octahedral geometry with the tridentate semicarbazone occupying three equatorial positions and the polypyridyl ligand coordinated in an equatorial/axial mode. Both complexes including dipyrido[3,2-a: 2′,3′-c]phenazine (dppz) as polypyridyl coligand showed IC₅₀ values in the μM range against Dm28c strain (epimastigotes) of Trypanosoma cruzi, causative agent of the disease, being as active as the anti-trypanosomal reference drug Nifurtimox. To get an insight into the trypanocidal mechanism of action of these compounds, DNA was evaluated as a potential parasite target and EPR, and ⁵¹V NMR experiments were also carried out upon aging aerated solutions of the complexes. Data obtained by electrophoretic analysis suggest that the mechanism of action of these complexes could include DNA interactions.     

Platinum(II) chloride indenyl complexes: electrochemical and biological evaluation

Four platinum(II) complexes of general formula [PtCl(??¹-C₉H₇)L₂] [where L₂ is 1,2-bis(diphenylphosphino)ethane (dppe) 1 or cycloocta-1,5-diene (cod) 3] and [PtCl₂L₂] (where L₂ is dppe 2 or cod 4) were studied. Inhibition growth assays on human tumor cell lines evidenced for 1 and 3 an antiproliferative effect and, interestingly, the cytotoxic effect exerted by 1 is similar to that of cisplatin. Electrochemical and NMR measurements allowed us to determine the structural and redox properties. Investigation of the mechanism of action responsible for the cytotoxicity demonstrated a weak capacity of interacting with DNA. Some experiments performed on rat liver mitochondria indicate that 1 acts as an inducer of the mitochondrial permeability transition, thus leading to the release of proapoptotic factors, such as cytochrome?c and apoptosis-inducing factor.     

Hydrophilic ligands derived from glucose: Synthesis, characterization and in vitro cytotoxic activity on cancer cells of Pt(II) complexes

Aiming to contribute to the design of new antitumoral drugs, we synthesized new hydrophilic Pt(II) complexes of general formula [PtCl₂(N,N′)] containing nitrogen bidentate amine-imine and di-imine ligands derived from glucose. Some chemical properties were discussed. The X-ray molecular structure of [PtCl₂(α-d-glucopyranoside-methyl-6-deoxy-6(2-(methylimino)methyl)pyridine) (D) was reported. [PtCl₂(β-d-glucopyranosylimine-N-(2-pyridinylmethyl))] (A), which is well-soluble both in organic solvents and in water, was tested for cytotoxicity.     

Synthesis and in vitro antitumour activity of PtCl2 complexes of pyridine- and quinoline-amine and -imine ligands and of carbocyclic ethylenediamine ligands

PtCl₂ complexes of pyridine- and quinoline- amine and -imine ligands and of carbocyclic ethylene- diamine ligands were prepared and characterized. Their antitumor activity was tested with respect to the hormone independent human mammary carcinoma cell line MDA-MB 231. The inhibition of the cell proliferation and the [³H]-thymidine incorporation was measured. Depending on the substituent patterns, the activities of the complexes in the present study range from inactive to highly active. The best ED₅₀-values approach the ED₅₀ of cisplatin.     

Cytotoxic palladium(II) complexes of 8-aminoquinoline derivatives and the interaction with human serum albumin

Palladium(II) complexes are potential antitumor metallodrugs for their chemical resemblance to platinum(II) complexes. Two palladium(II) complexes (1 and 2) in the formula of [PdLⁿCl] [L¹ = N-(tert-butoxycarbonyl)-l-methionine-N′-8-quinolylamide, L² = L-alanine-N′-8-quinolylamide] have been synthesized accordingly. The structures of the complexes were fully characterized by X-ray crystallography. The palladium(II) center in 1 is coordinated by two N atoms and an S atom from L¹ with one chloride anion as the leaving group; while that in 2 is coordinated by three N atoms from L² with one chloride anion as the leaving group. The interaction between complex 1 and human serum albumin (HSA) has been investigated using fluorescence and circular dichroism spectroscopies. The complex seems to react with HSA chiefly through hydrophobic and electrostatic interactions, and it does not alter the α-helical nature of HSA. The cytotoxicity of these complexes has been tested against the human cervical cancer (HeLa), human mammary cancer (MCF-7), and human lung cancer (A-549) cell lines. Complex 1 displays a cytotoxic activity comparable to that of cisplatin, but complex 2 is less active than cisplatin.