Synthesis, structural characterization, and antitumor activity of palladium(II) complexes containing a sugar unit

Six palladium(II) complexes as cisplatin derivatives with a sugar unit (D-glucose, D-galactose, D-mannose, D-xylose, and maltose) have been prepared. The structural features of the complexes have been characterized by NMR spectroscopy, elemental analysis, mass spectroscopy, and X-ray crystallography. The complexes have been tested for in vivo cytotoxicity against P388 cells implanted in mice. All of Pd compounds are apparently nontoxic. A T/C value of 120% was obtained for maltose derivative at the dose of 400 mg/kg, which indicates that the compound may be endowed with antitumor activity.     

Antimicrobial and anticancer activity of tetrahedral, chelated, diphosphine silver(I) complexes: comparison with copper and gold

Tetrahedral, bischelated Ag(I) diphosphine complexes [Ag(P-P)2]NO3, where P-P is Ph2P(CH2)2PPh2 (dppe), Et2P(CH2)2PPh2 (depe), and cis-Ph2P(CH = CH)PPh2 (dppey), are potently cytotoxic to B16 melanoma cells in vitro (IC50 4 microM) and exhibit good activity against ip P388 leukemia in mice. The complex [Ag(dppe)2]NO3 is active against M5076 reticulum cell sarcoma. The antibacterial and antifungal activities of Ag(I) diphosphine and related Cu(I) and Au(I) complexes were assessed. The complexes [Au(dppey)2]Cl, [Au(dppp)2]Cl and (CuCl)2(dppe)3 show modest activity against three of the 12 bacterial strains tested, but all complexes exhibit antifungal activity against three strains of C. albicans in a "defined" medium, [Ag(depe)2]NO3 and [Au(dppp)2]Cl having comparable activity to fungizone. Antifungal activity of the complexes is reduced in Sabouraud's broth medium, and lost altogether for the Ag(I) complexes. Reactions of some of the Ag(I) complexes with glutathione and blood plasma were studied by 31P NMR.     

Structure-antitumour activity relationships for new platinum complexes

Fourteen platinum (Pt) coordination complexes with different ligands, which include both Pt(II) and Pt(IV) complexes, were prepared, characterized and tested for their in vitro cytotoxic effects on KB cells and for their antitumour activity against some tumour systems (L1210 and P388 leukaemia, ADJ/PC6A plasma cell tumour and Yoshida sarcoma).The majority of the ligands were derivatives of aniline or pyridine, but complexes with tranylcypromine, guanethidine and octodrine were also synthetized.Depending on cytotoxicity the Pt-compounds could be divided into 3 groups. The compounds with a high cytotoxicity (ED₅₀ = 0.1–1 μg/ml) were also active against L1210 and P-388 leukaemia; a correlation between cytotoxicity and antitumour activity was not always observed.In these complexes the oxidation state of the Pt appears to be critical for their activity.     

Synthesis, spectroscopic, and cytotoxicity studies of some diamine and diimine platinum(II) complexes of diethyldithiocarbamate

Four new water soluble complexes of the formula [Pt(DA)(DDTC)]NO3 (where DA is 2,2'-bipyridine, 1,10-phenanthroline, 1,2-diaminopropane, or 1,2-diaminocyclohexane, and DDTC is diethyldithiocarbamate anion) have been synthesized by reaction of platinum-diamine/diimine diaqua complex with sodium diethyldithiocarbamate in molar ratio of 1:1. These complexes have been characterized by the chemical analysis, and ultraviolet-visible, infra-red and 1H NMR spectroscopy. The infrared and 1H NMR spectral studies of these complexes have ascertained the modes of binding of diamine/diimine and diethyldithiocarbamate to platinum. The molar conductance values of these platinum complexes in conductivity water suggest them to be 1:1 electrolytes. These four complexes and two other complexes containing ethylenediamine and 1,3-diaminopropane ligands have been tested against P-388 lymphocytic leukemic cells. Out of them only 2,2'-bipyridine and 1,10-phenanthroline complexes show 1.D.50 values less than cisplatin.     

Sodium periodate-induced T cell mitogenesis: an analysis of the requirement for Ia and IL 1

T lymphocytes oxidized with the mitogen sodium periodate undergo a proliferative response when cultured in the presence of Ia+ accessory cells. However, the exact role(s) the accessory cells play in such a response has not been clearly defined. We have evaluated the role of Ia and the requirement for interleukin 1 (IL 1) in periodate mitogenicity by using the Ia+ cloned tumor cell lines P388AD (Ia+, IL 1 inducible) and P388NA (Ia+, IL 1 noninducible) as accessory cells. P388AD but not P388NA was able to supply accessory cell function to periodate-treated T cells, suggesting that Ia expression alone was not sufficient to reconstitute a response. Monoclonal anti-I-Ad and anti-I-Ed antibody blocked the accessory cell function of P388AD. In addition, monoclonal antibody GK 1.5, directed against the T cell determinant L3T4a, blocked the P388AD/periodate-treated T cell interaction, confirming that this interaction was restricted by class II molecules. Although Ia expression was required, the response was not major histocompatibility complex (MHC) restricted, because allogeneic as well as syngeneic macrophages were capable of supplying accessory cell function to periodate-treated T cells. Exogenous IL 1 alone was able to trigger periodate-treated T cells, suggesting that Ia was required for the induction of IL 1 synthesis by the accessory cells. Furthermore, purified IL 2, devoid of IL 1 activity, was able to fully reconstitute the proliferative response of accessory cell-depleted oxidized T cells to a level equal to that of whole spleen accessory cells or P388AD. These data suggest that periodate-treated T cells can proliferate with IL 1 alone and that Ia+ accessory cells in periodate-mediated T cell mitogenicity may function in the release of IL 1 and the induction of IL 2 synthesis by the T cells.     

Medicarpin and millepurpan,two flavonoids isolated from Medicago sativa,induce apoptosis and overcome multidrug resistance in leukemia P388 cells

BackgroundHigh consumption of flavonoids has been associated with a decrease risk of cancer. Alfalfa (Medicago sativa) leaves have been widely used in traditional medicine and is currently used as a dietary supplement because of their high nutrient content. We previously reported the cytotoxic activity of alfalfa leaf extracts against several sensitive and multidrug resistant tumor cell lines.Hypothesis/purposeWe aimed to determine whether medicarpin and millepurpan, two isoflavonoids isolated from alfalfa leaves, may have pro-apoptotic effects against drug-sensitive (P388) and multidrug resistant P388 leukemia cells (P388/DOX).Study design/methodsCells were incubated with medicarpin or millepurpan for the appropriate time. Cell viability was assessed by the MTT assay. DNA fragmentation was analyzed by agarose gel electrophoresis. Cell cycle analysis was realized by flow cytometry technics. Caspases 3 and 9 activities were measured using Promega caspACE assay kits. Proteins and genes expression were visualized respectively by western-blot using specific antibodies and RT-PCR assay.ResultsP-glycoprotein-expressing P388/DOX cells did not show resistance to medicarpin (IC₅₀ ≈ 90 µM for P388 and P388/DOX cells) and millepurpan (IC₅₀ = 54 µM and 69 µM for P388 and P388/DOX cells, respectively). Treatment with medicarpin or millepurpan triggered apoptosis in sensitive as well as multidrug resistant P388 cells. These effects were mediated through the mitochondrial pathway by modifying the balance pro/anti-apoptotic proteins. While 3 µM doxorubicin alone could not induce cell death in P388/DOX cells, concomitant treatment with doxorubicin and subtoxic concentration of medicarpin or millepurpan restored the pro-apoptotic cascade. Each compound increased sensitivity of P388/DOX cells to doxorubicin whereas they had no effect in sensitive P388 cells. Vinblastine cytotoxicity was also enhanced in P388/DOX cells (IC₅₀ = 210 nM to 23 and 25 nM with medicarpin and millepurpan, respectively). This improved sensitivity was mediated by an increased uptake of doxorubicin in P388/DOX cells expressing P-gp. P-gp expression was not altered by exposure to medicarpin and millepurpan.ConclusionThese data indicate that medicarpin and millepurpan possess pro-apoptotic properties and potentiate the cytotoxicity of chemotherapy drugs in multidrug resistant P388 leukemia cells by modulating P-gp-mediated efflux of drugs. These flavonoids may be used as chemopreventive agents or as sensitizer to enhance cytotoxicity of chemotherapy drugs in multidrug resistant cancer cells.     

Modulation of mitomycin C resistance by glutathione transferase inhibitor ethacrynic acid.

This study was undertaken to elucidate the mechanism(s) of cross-resistance (4.9-fold) to mitomycin C (MMC) in a multi-drug-resistant cell line, P388/R-84. Intracellular accumulation of MMC by sensitive (P388/S) and P388/R-84 cells was comparable. Despite a 32% reduction in NADPH cytochrome P-450 reductase activity (responsible for MMC activation) in P388/R-84 cells, the rate of MMC bio-reduction by sensitive and resistant cells was similar. These results suggested that MMC resistance in P388/R-84 cell line must depend on factors other than impaired drug accumulation or bio-activation. Recent studies suggest that glutathione transferase (GST) dependent drug detoxification also contributes to cellular resistance of a variety of alkylating agents. Even though overexpression of GST has been noted in some MMC resistant tumor cells, it is not known if its level affects sensitivity to MMC. We have, therefore, determined the effect of ethacrynic acid (an inhibitor of GST activity) treatment on MMC cytotoxicity in P388/R-84 cells, which have about 2-fold higher GST activity than P388/S cells. The IC50 value for the inhibition of GST activity in vitro by ethacrynic acid (EA) was 16.5 microM (5 micrograms/ml). A depletion in intracellular GSH was also observed by treating P388/R-84 cells with EA alone or in combination with MMC. A non-toxic concentration of EA (1 microgram/ml; 3.3 microM) increased MMC cytotoxicity by 36% in P388/R-84 cells. MMC cytotoxicity was increased 2-fold by EA treatment in glutathione (GSH)-depleted P388/R-84 cells. These results suggest that GST mediated drug inactivation may represent another important mechanism of MMC resistance.     

DNA targeted platinum complexes: synthesis, cytotoxicity and DNA interactions of cis-dichloroplatinum(II) complexes tethered to phenazine-1-carboxamides

A series of intercalator-tethered platinum(II) complexes PtLCl2 have been prepared, where L are the diamine ligands N-[2-[(aminoethyl)amino]ethyl]-phenazine-1-carboxamide, N-[3-[(2-aminoethyl)amino]propyl]-phenazine-1-carboxamide, N-[4-[(2-aminoethyl)amino]butyl]-phenazine-1-carboxamide and N-[5-[(aminoethyl)amino]pentyl]-phenazine-1-carboxamide. Measurements of the time-course of unwinding of supercoiled pUC19 plasmid DNA by the phenazine complexes PtLCl2 reveal that the presence of the intercalator leads to enhanced rates of DNA platination when compared with the complex Pt(en)Cl2. The platinum(II) complexes where the polymethylene linker chain contains three, four or five carbon atoms are considerably more cytotoxic against murine P388/W than either cisplatin, Pt(en)Cl2, or the metal-free ligands themselves.     

Circular dichroism study of the interaction of mitoxantrone, ametantrone and their Pd(II) complexes with deoxyribonucleic acid

The interaction of mitoxantrone, ametantrone and their Pd(II) complexes with DNA have been studied using absorption and circular dichroism spectroscopy. We have shown that mitoxantrone forms with Pd(II) a complex in which two Pd(II) ions are bound to two molecules of drug (D1 and D2). One Pd(II) ion is bound to the two nitrogens of the side chain on C-5 of molecule D1 and to the two nitrogens of the side chain on C-5 of molecule D2, whereas the second Pd(II) ion is bound to the nitrogens of the side chain on C-8 of molecule D1 and of molecule D2. The same complex is formed between Pd(II) and ametantrone. The stability constants for these complexes are, respectively, beta M = (1.4 +/- 0.5).10(19) and beta A = (2.5 +/- 0.5).10(18). They display antitumor activity against P 388 leukemia which compares with that of the free drugs. Interactions of the free drugs with DNA have been studied. Mitoxantrone and ametantrone are not optically active by themselves. However, through interaction with DNA, there is an induction of optical activity within the electronic transitions of both drugs. At a nucleotide/drug molar ratio lower than about 5 a CD signal of the couplet type is observed, suggesting that there is a coupling between the pi----pi transitions of the molecules of drugs intercalated between the base pairs. This coupling disappears when the molar ratio is increased. The interactions of the Pd(II) complexes with DNA do not give rise to induction of optical activity within the electronic transition of the drugs, indicating that the presence of the metal ion prevents the intercalation of the drugs between the base pairs.     

Reactive-site specificity of human kallistatin toward tissue kallikrein probed by site-directed mutagenesis

Kallistatin is a serine proteinase inhibitor that forms complexes with tissue kallikrein and inhibits its activity. In this study, we compared the inhibitory activity of recombinant human kallistatin and two mutants, Phe388Arg (P1) and Phe387Gly (P2), toward human tissue kallikrein. Recombinant kallistatins were expressed in Escherichia coli and purified to apparent homogeneity using metal-affinity and heparin-affinity chromatography. The complexes formed between recombinant kallistatins and tissue kallikrein were stable for at least 150 h. Wild-type kallistatin as well as both Phe388Arg and Phe387Gly mutants act as inhibitors and substrates to tissue kallikrein as analyzed by complex formation. Kinetic analyses showed that the inhibitory activity of Phe388Arg variant toward tissue kallikrein is two-fold higher than that of wild type (P1Phe), whereas Phe387Gly had only 7% of the inhibitory activity toward tissue kallikrein as compared to wild type. The Phe388Arg variant but not wild type inhibited plasma kallikrein's activity. These results indicate that P1Arg variant exhibits more potent inhibitory activity toward tissue kallikrein while wild type (P1Phe) is a more selective inhibitor of tissue kallikrein. The P2 phenylalanine is essential for retaining the hydrophobic environment for the interaction of kallistatin and kallikrein.     

Iron(III)-adriamycin and Iron(III)-daunorubicin complexes: physicochemical characteristics, interaction with DNA, and antitumor activity

Fe(III) complexes of two anthracyclines, adriamycin and daunorubicin, have been studied. Using potentiometric and spectroscopic measurements, we have shown that adriamycin and daunorubicin form two well-defined species with Fe(III), which can be formulated as respectively Fe(HAd)3 and Fe(HDr)3. In these formulas, HAd and HDr stand for adriamycin and daunorubicin in which the 1,4-dihydroxy-anthraquinone moiety is half-deprotonated. Both complexes are six-membered chelates. The stability constant is beta = (2.5 +/- 0.5) X 10(28) for both complexes. Interaction with DNA has been studied showing that, despite strong coordination to Fe(III), anthracyclines are able to intercalate between DNA bases pairs, releasing the metal. These complexes display antitumor activity against P 388 leukemia that compares with that of the free drug. Fe(HAd)3, unlike adriamycin, does not catalyze the flow of electrons from NADH to molecular oxygen through NADH dehydrogenase. Moreover, it is shown that the triferric adriamycin compound so called "quelamycin" is in fact a mixture of Fe(HAd)3 and polymeric ferric hydroxide.     

Synthesis of water-soluble ruthenium porphyrins as DNA cleavers and potential cytotoxic agents

 Three new water-soluble ruthenium porphyrin complexes have been prepared and characterized, one with a cationic ligand, Ru(TMPyP), and two others with anionic ligands, Ru(p–COOH-PP) and Ru(TPPS). These different complexes and their manganese and iron analogues were tested in vivo as potential antitumor agents with mice bearing P388 leukemia cells, but these complexes have no significant antitumor activity. The nuclease activity of Ru(TMPyP) and Ru(p–COOH-PP) was evaluated on supercoiled plasmid DNA after activation by a reducing agent (ascorbate) in the presence of air or by potassium monopersulfate. No significant activity was evidenced for these ruthenium complexes, in contrast with the already known nuclease activity of the manganese and iron derivatives of TMPyP. Received: 15 November 1996 / Accepted: 7 April 1997     

Shikimic acid complexes of platinum. Preparation, reactivity, and antitumor activity of (R,R-1,2-diaminocyclohexane) bis(shikimato) platinum(II). Evidence for a novel rearrangement involving platinum-carbon bond formation

The complex (R,R-1,2-diaminocyclohexane)bis(shikimato)platinum(II) (shikimato = the anion of 3R,4S,5R-trihydroxy-1-cyclohexene-1-carboxylic acid), I, has been synthesized and purified by high performance liquid chromatography (HPLC). The complex is only moderately stable in aqueous solution. Its major hydrolysis product, also purified by HPLC, is proposed to be a unique complex type in which a single shikimate group is coordinated through both the carboxylate oxygen and the C(2) vinylic carbon of the shikimate moiety [Pt(R,R-dach)(O,C-shikimato)], II. In vitro, complex I is active against L1210 leukemia and against an L1210 cell line with acquired resistance to cisplatin. In vivo, the complex is active against L1210, P388, and B16 melanoma; this activity is highly schedule-dependent. Complex II is also active against L1210 leukemia.     

Synthesis, characterization, and antitumor activity of iron(II) and iron(III) complexes of alpha-N-heterocyclic carboxaldehyde thiosemicarbazones

Complexes of iron(II) and iron(III) with 1-formylisoquinoline thiosemicarbazone (1-iqtsc-H), 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone (4-Me-5-NH2-1-iqtsc-H) and 4-(m-aminophenyl)-2-formylpyridine thiosemicarbazone (4-m-NH2ph-2-pytsc-H) were synthesized and characterized by elemental analysis, conductance measurements, magnetic susceptibilities (from room temperature down to liquid N2 temperature), and M?ssbauer, electronic, and infrared spectral studies. On the basis of these studies, a highly distorted, high-spin, five-coordinate structure for Fe(HL)SO4 (HL = 1-iqtsc-H, 4-Me-5-NH2-1-iqtsc-H or 4-m-NH2ph-2-pytsc-H) and a distorted, low-spin, octahedral structure for Fe(HL)Cl2 are suggested. The EPR spectra of iron(III) complexes show that all have dxy low-spin ground state. All these complexes have been screened for their antitumor activity against the P 388 lymphocytic leukemia test system in mice and have been found to possess significant activity at the dosages employed.     

Some potential anticancer palladium(II) complexes of 2,2'-bipyridine and amino acids

Nine new palladium(II) complexes of the formula [Pd(bipy)(AA)]n+ (where bipy is 2,2'-bipyridine, AA is an anion of L-cysteine, L-aspartic acid, L-glutamic acid, L-methionine, L-histidine, L-arginine, L-phenylalanine, L-tyrosine, or L-tryptophan, and n = 0 or 1) have been synthesized by interaction of [Pd(bipy)Cl2] with an appropriate sodium salt of amino acid in water. These palladium(II) complexes have been characterized by chemical analysis and by visible, infrared, and 1H NMR spectroscopy. The modes of binding of amino acids in these palladium complexes have been ascertained by infrared and 1H NMR spectroscopy. The molar conductances of these complexes in water suggest that they are either nonelectrolytes or 1:1 electrolytes. These palladium complexes have shown growth inhibition against L1210 lymphoid leukemic, P388 lymphocytic leukemic, Sarcama 180, and Ehrlich ascites tumor cells. Some of these complexes show I.D.50 values comparable to or lower than cis-diamminedichloroplatinum(II).     

Synthesis and antiproliferative activity in vitro of novel (2-butynyl)thioquinolines

The series of new acetylenic thioquinolines containing propargyl, 2-butynyl, 4-bromo-2-butynyl, and 4-hydroxy-2-butynyl groups has been prepared and tested for antiproliferative activity in vitro against human [SW707 (colorectal adenocarcinoma), CCRF/CEM (leukemia)] and murine [P388 (leukemia), B16 (melanoma)] cancer lines. All the compounds obtained exhibited antiproliferative activity. The most active compounds 7, 16, 17, and 19 have the ID(50) values ranging from 0.2 to 4.6 microg/ml comparable to that of cisplatin used as reference compounds.     

Synthesis and characterization of water-insoluble and water-soluble dibutyltin(IV) porphinate complexes based on the tris(pyridinyl)porphyrin moiety,their anti-tumor activity in vitro and interaction with DNA

The water-insoluble and water-soluble organotin(IV)porphinate complexes based on the tris-(4-pyridinyl)porphyrin and tris(N-methyl-4-pyridiniumyl)porphyrin moieties were synthesized and characterized by elemental analysis, (1)H NMR, IR and electrospray ionization mass spectra. The in vitro activity of the compounds against P388 leukemia and A-549 was determined. The results show that the anti-tumor activities of organotin(IV)porphinate is related to the water solubility of the compounds and the central ion in the porphyrin ring. The interaction between the water-soluble dibutyltin(IV) porphinate (7 and 10) complexes and DNA has been investigated. The result shows that compounds 7 and 10 cause DNA hypochromism measured by A(260), a slight increase in the viscosity of the DNA, and an increase in the melting point of DNA by 2.9 and 1.6 degrees C, respectively at DNA(base)/Drug(Por) ratios of 60. The binding constants to DNA were 1.35+/-0.16 x 10(7) M(-1) (7) and 1.45+/-0.12 x 10(6) M(-1) (10) determined using EB competition method based on the porphyrin concentration, which is 20 and five times greater than that of precursor porphyrins [5-p,o-(carboxy)methoxyphenyl-10,15,20-tris(N-methyl-4-pyridiniumyl)] porphyrin (p,o-tMPyPac) to DNA. Electrophoresis test shows that the compounds cannot cleave the DNA. According to the electrophoresis test result and all the above results, the cytotoxic activity against P388 and A-549 tumor cells appears not to come from the cleavage of DNA caused by the compounds but from the high affinity of compounds to DNA.     

Metal anthracycline complexes as a new class of anthracycline derivatives. Pd(II)-adriamycin and Pd(II)-daunorubicin complexes: physicochemical characteristics and antitumor activity

Pd(II) complexes of two anthracyclines, adriamycin and daunorubicin, have been studied. Using potentiometric absorption, fluorescence, and circular dichroism measurements, we have shown that adriamycin can form two complexes with Pd(II). The first complex (I) involves two molecules of drug per Pd(II) ion; one of the molecules is chelated to Pd(II) through the carbonyl oxygen on C12 and the phenolate oxygen on C11, and the other one is bound to Pd(II) through the nitrogen of the amino sugar. This complexation induces a stacking of the two molecules of drug. In the second complex (II), two Pd(II) ions are bound to two molecules of drug (A1 and A2). One Pd(II) is bound to the oxygen on the carbons C11 and C12 of molecule A1 and the amino sugar of molecule A2 whereas the second Pd(II) ion is bound to the oxygen on C11 and C12 of molecule A2 and the amino sugar of molecule A1. The same complexes are formed between Pd(II) and daunorubicin. The stability constant for complex II is beta = (1.3 +/- 0.5) X 10(22). Interaction with DNA has been studied, showing that almost no modification of the complex occurred. This complex displays antitumor activity against P-388 leukemia that compares with that of the free drug. Complex II, unlike adriamycin, does not catalyze the flow of electrons from NADH to molecular oxygen through NADH dehydrogenase.     

Polyelectrolyte complexes between (cross-linked) N-carboxyethylchitosan and (quaternized) poly[2-(dimethylamino)ethyl methacrylate]: preparation, characterization, and antibacterial properties

Novel polyelectrolyte complexes (PECs) between N-carboxyethylchitosan (CECh) and well-defined (quaternized) poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) have been obtained. The modification of chitosan into CECh allows the preparation of PECs in a pH range in which chitosan cannot form complexes. The CECh/PDMAEMA complex is formed in a narrow pH range around 7. The quaternization of the tertiary amino groups of PDMAEMA enables complex formation with CECh both in neutral and in alkaline medium. Cross-linked CECh is also capable of forming complexes with (quaternized) PDMAEMA. The antibacterial activity of (cross-linked) CECh, (quaternized) PDMAEMA, and their complexes against Escherichia coli has been evaluated. In contrast to (quaternized) PDMAEMA, (cross-linked) CECh exhibits no antibacterial activity. The complex formation between cross-linked CECh and (quaternized) PDMAEMA results in a loss of the inherent antibacterial activity of the latter in neutral medium. In acidic medium, the complexes exhibit strong antibacterial activity due to complex disintegration and release of (quaternized) PDMAEMA.     

Synthesis, characterization and antitumor properties of some metal complexes of 3- and 5-substituted salicylaldehyde 2-pyridinylhydrazones

Complexes of Mn(II), Fe(II), Co(II), Ni(II), Cu(II), Zn(II), and Pt(II) with 3- and 5-substituted salicylaldehyde 2-pyridinylhydrazones (XSPH, X = H, 3-NO2, 3-CH3O, 5-Br, 5-Cl, 5-CH3, or 5-NO2) have been prepared and characterized by elemental analysis, conductance measurements, magnetic moments (300-78 K), and spectral studies. On the basis of these studies a monomeric, high-spin, distorted octahedral structure for Mn(XSPH)2 and Fe(XSPH)2, a dimeric, high-spin, five-coordinate structure for Co(XSBH)Cl, a dimeric, low-spin, five-coordinate structure for Ni(XSPH)Cl and Zn(XSPH)(OAc), and a square-planar structure for M(XSPH)Cl.H2O (M = Cu(II) or Pt(II] complexes are suggested. The polycrystalline ESR spectra of Cu(II) complexes are isotropic and suggest dx2-y2 ground state in square-planar stereochemistry. M?ssbauer spectral results indicate distorted octahedral structure for iron(II) complexes. All the metal(II) complexes have been screened for their antitumor activity against P388 lymphocytic leukemia test system in mice and have been found to possess no significant activity at the dosages used.