Iodophenyl tagged sphingosine derivatives: Synthesis and preliminary biological evaluation

A facile synthesis of six 4-iodophenyl tagged sphingosine (SP) derivatives bearing alkyl chain lengths from 6 to 13 is described. The key steps for the assembly of these molecules, 5a–f, are Suzuki–Miyaura cross-coupling and cross-metathesis reactions. The feasibility of radiolabeling was demonstrated by synthesizing two ¹²⁵I labeled compounds, [¹²⁵I]5c and [¹²⁵I]5e. In vitro enzyme assays indicated that the molecules, 5c–e, are potent inhibitors. Thus, they deserve further evaluation as potential radioactive probes for tumor imaging.     

Synthesis and reactivity of mixed pentafluorophenyl platinum(I)-palladium(I) derivatives

XPd(μ-dppm)₂Pt(C₆F₅) (X = Cl (I), Br (II)) have been prepared by reacting Pd₂(dba)₃·CHCl₃ and PtX- (C₆F₅)(η¹-dppm)₂. Reaction of complex I with SnCl₂ gives the SnCl₃⁻ derivative, whilst ligands L (PPh₃, P(OPh)₃, SbPh₃) render the cationic complexes. The species R₂N⁺, SO₂ or MeOOC)CCCOOMe insert into the PdPt bond of I to give A-frame Pd(II)- Pt(II) complexes. The reactions of CIPd(μ-dppm)₂- Pt(C6F₅) with isonitriles CNR (R = p-Tol, Cy) lead to products containing either terminal or inserted isocyanide or both.     

New antitumor titanocene derivatives containing hydrophilic ligands

Four titanocene derivatives containing hydrophilic ligands were tested for antiproliferative activity against Ehrlich ascites tumor in mice. The new compounds (C₅H₅)₂TiCl(p-SC₆H₄NH₃⁺Cl^?) (I) and (C₅H₅)₂Ti(p-SC₆H₄NH₃⁺Cl^?)₂ (II), containing hydrochlorinated p-aminothiophenolate ligands, and the known compounds (C₅H₅)₂Ti(cis-OOCCHCHCOOH)₂ (III) and (C₅H₅)₂Ti(OOCCCl₃)₂ (IV) containing the carboxylic acid anions hydrogen- maleinate and trichloroacetate as acido ligands, induced maximum cure rates of 100%. The T.I. values amounted to 4.4–4.6 (I), 3.5–4.1 (II), 3.7– 3.8 (III) and 5.5 (IV), and were slightly increased in comparison to (C₅H₅)₂TiCl₂ (T.I. = 3.3). The complexes I–III were rather soluble in water and equally active in a DMSO/saline (1/9, v/v) mixture, in pure saline and in buffered solutions. In the case of IV, the toxicity was considerably low (LD₅₀,440 mg/kg; LD₁₀₀, 500 mg/kg) in relation to (C₅H₅)₂TiCl₂ (LD₅₀, 100 mg/kg; LD₁₀₀, 140 mg/kg).     

A characterization of alpha-bungarotoxin binding in the brain of the horseshoe crab, Limulus polyphemus

The binding of ¹²⁵I-labeled α-bungarotoxin to membrane fragments prepared from Limulus brain tissue has been investigated. Toxin binding approaches saturation in the range of 30 to 40 nm, with maximum binding of 2 to 6 pmol/mg of protein. The saturation kinetics and the rate of displacement of bound toxin are consistent with multiple toxin binding sites. Pharmacological studies show that binding is inhibited by both cholinergic agonists and antagonists, I₅₀′s for inhibition by d-tubocurarine, nicotine, decamethonium, carbachol, and atropine are 2 × 10^?6, 7 × 10^?6, 2 × 10^?5, 6 × 10^?4, and 3 × 10^?4m, respectively. Nicotinic ligands inhibited binding much more effectively than muscarinic ligands. Toxin binding activity was solubilized with Triton X-100. Velocity sedimentation analysis of the solubilized activity revealed three separate components. Seventy to eighty percent of the binding activity had a sedimentation coefficient of 8.6 S. The remaining activity was composed of two components with sedimentation coefficients of 15.1 and 17 S.     

Synthesis and biological evaluation of radio-iodinated benzimidazoles as SPECT imaging agents for NR2B subtype of NMDA receptor

In this study, the benzimidazole derivatives were synthesized and evaluated as imaging agents for the NR2B subtype of NMDA receptor. Among these ligands, 2-{[4-(4-iodobenzyl)piperidin-1-yl]methyl}benzimidazol-5-ol (8) and N-{2-[4-(4-iodobenzyl)-piperidin-1-ylmethyl]benzoimidazol-5-yl}-methanesulfonamide (9) exhibited high affinity for the NR2B subunit (K_i values; 7.28 nM for 8 and 5.75 nM for 9). In vitro autoradiography experiments demonstrated high accumulation in the forebrain regions but low in the cerebellum for both [¹²⁵I]8 and [¹²⁵I]9. These regional distributions of the radioligands correlated with the expression of the NR2B subunit. The in vitro binding of these ligands was inhibited by NR2B antagonist but not by other site ligands, which suggested the high selectivity of [¹²⁵I]8 and [¹²⁵I]9 for the NR2B subunit. In mice, the regional brain uptakes of [¹²⁵I]8 and [¹²⁵I]9 at 5–180 min after administration were 0.42–0.56% and 0.44–0.67% dose/g, respectively. The brain-to-blood ratio of [¹²⁵I]8 at 180 min was reduced by 34% in the presence of non-radioactive ligands and by 59% in the presence of the NR2B ligand Ro-25,6981. These results indicated that [¹²⁵I]8 could be partially bound to the NR2B subunit in vivo. Although the brain uptake of these benzimidazole derivatives was too low to allow for in vivo SPECT imaging, these compounds might be useful scaffolds for the development of imaging probes specific for the NMDA receptors.     

Platinum(II) complexes with aryl tellurols and diaryl ditellurides: Syntheses and spectral investigations

Arytellurol complexes [PtCl(TeAr)(PPh₃)₂] (I) and [Pt(TeAr)₂(PPh₃)₂] (II) are readily obtained from cis-[PtCl₂(PPh)₃)₂] and NaTeAr (Ar = C₆H₅, 4-CH₃OC₆H₄ and 4-CH₃CH₂OC₆H₄) in ethanolbenzene at room temperature. ³¹P NMR spectra of (I) and (II) indicate their trans configuration in solution. Metathetical reactions between I (Ar = 4-CH₃OC₆H₄) and NaX (X = I, Br, SCN) occur in methanol to give [Pt(X)(TeC₆H₄OCH₃-4)(PPh₃)₂]. ¹H NMR shows that equimolar proportions of NaTeC₆H₅, NaTeC₆H₄OCH₂CH₃-4 and cis-[PtCl₂(PPh₃)₂] give a mixture of three complexes: II, Ar = C₆H₅; II, Ar = 4-CH₃CH₂OC₆H₄; and [Pt(TeC₆H₅)(TeC₆H₄OCH₂CH₃-4)(PPh₃)₂]. Polymeric complexes [PtCl(TeAr)]_n (III) and [Pt(TeAr)₂]_n (IV) result from reaction between K₂[PtCl₄] and NaTeAr in aqueaous ethanol. They react with excess of PPh₃ in CDCl₃ to yield monomeric complexes I and II respectively which were characterized in situ by ¹H and ³¹P NMR of the reaction mixtures. IR spectra indicate the presence of bridging chloride ligands in III. An alternating chloride and tellurol bridged chain structure for III and a tellurol bridged for IV have been proposed. Reaction between equimolar amounts of III and PPh₃ in dichloromethane yielded a tellurol bridged dimeric complex [PtCl(μ-TeAr)(PPh₃)]₂ (V) with terminal chloride ligand as suggested by IR study. Ethanolic solutions of diarylditellurides also react readily with an aqueous solution of K₂[PtCl₄] at 10 °C to give complexes for which the structure trans-[PtCl₂(ArTeTeAr)₂] (VI) is suggested from their elemental analyses, IR, Raman (in one case only), ¹H, ¹²⁵Te (in one case only), and ¹⁹⁵Pt NMR spectra and reactions with triphenylphosphine which liberated free ditellurides. At 40 °C or above the same ditellurides form polymeric complexes III with K₂[PtCl₄] in aquaeous ethanol.     

Synthesis and evaluation of indolinyl- and indolylphenylacetylenes as PET imaging agents for beta-amyloid plaques

Two new phenylacetylene derivatives, 5-((4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)phenyl)ethynyl)indoline 8 and 5-((4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)phenyl)ethynyl)-1H-indole 14, targeting β-amyloid (Aβ) plaques have been prepared. In vitro binding carried out in tissue homogenates prepared from postmortem AD brains with [¹²⁵I]IMPY (6-iodo-2-(4′-dimethylamino-)phenyl-imidazo[1,2-a]pyridine) as the radioligand indicated good binding affinities (K_i = 4.0 and 1.5 nM for 8 and 14, respectively). Brain penetration of the corresponding radiofluorinated ligands, evaluated in the normal mice, showed good initial brain penetration (4.50 and 2.43% ID/g (injected dose/gram) for [¹⁸F]8 and [¹⁸F]14 at 2 min after injection) with moderate to low washout rates from the brain (1.71% ID/g at 2 h and 2.10% ID/g at 3 h, respectively). Autoradiography and homogenate binding studies demonstrated the high specific binding of [¹⁸F]14 to the Aβ plaques; however, [¹⁸F]8 showed low specific binding. These preliminary results identified that indolylphenylacetylene, 14, may be a good lead for further structural modification to develop a useful Aβ plaque imaging agent.     

Synthesis, reactivity, and structures of dialuminum complexes containing linked ketiminate ligands

Linked bis(ketimine) (1) can be prepared with the reaction of excess 2,4-pentanedione and 4,4′-methylene-bis(2,6-diisopropylaniline) in methanol in the presence of catalytic amount of formic acid. The dialuminum alkyl complexes containing the linked bis(ketiminate) dianionic ligands, [OC(Me)CHC(Me)N(2,6-ⁱPr₂C₆H₂-4)AlR₂]₂CH₂ (2, R = Me; 3, R = Et), were prepared by a reaction of 2 equiv AlR₃ with [OC(Me)CHC(Me)NH(2,6-ⁱPr₂C₆H₂-4)]₂CH₂ in methylene chloride. Reactions of 2 with 2 and 4 equiv of I₂ gave corresponding aluminum iodo complexes 4 and 5, respectively. Treatment of 5 with 2 equiv of AgBF₄, however, gave a diboron complex, [OC(Me)CHC(Me)N(2,6-ⁱPr₂C₆H₂-4)BF₂]₂CH₂ (6), in 18% isolated yield. All new complexes have been characterized by ¹H and ¹³C NMR spectroscopy and complexes 2, 3, and 6 are also confirmed by X-ray diffraction.     

Effect of prostaglandin I2 and related compounds on vascular permeability response in granuloma tissues

The effects of prostaglandin I₂, 6-ketoprostaglandin F_1α, prostaglandin E₁ and thromboxane B₂ on the vascular permeability response in rat carrageenin granuloma were studied with the aid of ¹³¹I- and ¹²⁵I-human serum albumin as indicators for the measurement of local vascular permeability.A single injection of 5 μg of prostaglandin I₂ methyl ester or I₂ sodium salt into the locus of the granulomatous inflammation elevated local vascular permeability 2.0–2.5 times over the control within 30 min. The potency was equal to that of the positive control prostaglandin E₁ which has been known to be the most potent mediator in this index among several candidate prostaglandins for chemical mediator of inflammation. The other prostaglandin and thromboxane B₂ tested were essentially inactive.     

Benzimidazole derivatives as NSO ligands for the fac-[M(CO)3] (M = Re, Tc)

Two rhenium(I) tricarbonyl complexes with the tridentate monoanionic NSO ligands, 4-(benzimidazol-2-yl)-3-thiabutanoic acid (complex 3) and [1-(11-carboxyundecanyl)-4-(benzimidazol-2-yl)]-3-thiabutanoic acid (complex 4) were synthesized and characterized by spectroscopic methods and elemental analysis. X-ray crystallographic analysis of complex 3 revealed a distorted octahedral geometry around rhenium defined by the three facially bound CO groups and the NSO donor atom set of the tridentate ligand. The analogous technetium-99m complexes (complexes 5 and 6) were also prepared quantitatively by reaction of the NSO ligands with the fac-[^99mTc(H₂O)₃(CO)₃]⁺ synthon and their identity was established by chromatographic comparison to their rhenium congeners. Biodistribution in mice of complex 6 bearing the fatty acid chain showed significant heart uptake (6.26 ± 0.79% ID/g p.i.) at 1 min accompanied, however, with a heart:blood ratio below 1.     

Compartmental pyrazolate ligands providing two adjacent tris(pyridylalkyl)amine-type binding pockets and their dicopper(II) fluoride complexes featuring extremely short intramolecular O-H?F bridges

A set of pyrazolate-based compartmental ligands HL²-HL⁵ with pendent (pyridylalkyl)amine side arms in the 3- and 5-positions of the pyrazole has been prepared. The ligands differ by the number and lengths of the pyridylalkyl arms, and they can be described as dinucleating versions of well-known ligands such as tris(pyridylmethyl)amine (tpma) or tris(pyridylethyl)amine (tpea). Reaction of HL², HL³ or HL⁵ with Cu(BF₄)₂ · 6H₂O in the presence of base causes fluoride abstraction from the tetrafluoroborate and gives dicopper(II) complexes 1, 2, and 3a and b, respectively, which feature extremely short intramolecular F?HOMe or F?HOH bridges (d(F?O)=2.384(6)-2.507(3)). Molecular structures of all four complexes have been elucidated by X-ray crystallography and are compared to their mononuclear analogues. The influence of the intramolecular F?HO bridge on Cu-F and Cu-O bond lengths as well as on other structural characteristics is discussed.     

Anion effects on construction of Zn compounds with a chelating ligand bis(2-pyridylmethyl)amine and their catalytic activities

Three Zn^II complexes containing bispicam ligands (bispicam = bis(2-pyridylmethyl)amine), [Zn(bispicam)₂](NO₃)₂·2CH₃OH 4A, [Zn(bispicam)(NO₃)₂] 4B, and [Zn(bispicam)₂](OTf)₂6, were obtained, and their structures were determined by X-ray crystallography. Complexes of the general formulation [Zn(bispicam)₂]X₂ (X = Cl⁻ (1), Br⁻ (2), I⁻ (3), NO₃⁻ (4A), ClO₄⁻ (5), and OTf⁻ (6)) show fac geometric isomers (a) or enantiomers (c) and (d) according to anions. Moreover, complexes 4-6 could carry out the catalytic transesterification of a range of esters with methanol under the mild conditions. Importantly, the catalyst 4B with an unsaturated structure has shown better efficiency than the catalysts, 4A, 5, and 6, having saturated structures. To explain this reactivity difference, two different reaction mechanisms have been proposed (metal-based vs. amide N-H-based).     

Synthesis and evaluation of novel radioiodinated PSMA targeting ligands for potential radiotherapy of prostate cancer

Radioligand therapy (RLT) using prostate-specific membrane antigen (PSMA) targeting ligands is an attractive option for the treatment of Prostate cancer (PCa) and its metastases. We report herein a series of radioiodinated glutamate-urea-lysine-phenylalanine derivatives as new PSMA ligands in which l-tyrosine and l-glutamic acid moieties were added to increase hydrophilicity concomitant with improvement of in vivo targeting properties. Compounds 8, 15, 19a/19b and 23a/23b were synthesized and radiolabeled with ¹²⁵I by iododestannylation. All iodinated compounds displayed high binding affinities toward PSMA (IC₅₀ = 1–13 nM). In vitro cell uptake studies demonstrated that compounds containing an l-tyrosine linker moiety (8, 15 and 19a/19b) showed higher internalization than MIP-1095 and 23a/23b, both without the l-tyrosine linker moiety. Biodistribution studies in mice bearing PC3-PIP and PC3 xenografts showed that [¹²⁵I]8 and [¹²⁵I]15 with higher lipophilicity exhibited higher nonspecific accumulations in the liver and intestinal tract, whereas [¹²⁵I]19a/19b and [¹²⁵I]23a/23b containing additional glutamic acid moieties showed higher accumulations in the kidney and implanted PC3-PIP (PSMA+) tumors. [¹²⁵I]23b displayed a promising biodistribution profile with favorable tumor retention, fast clearance from the kidney, and 2–3-fold lower uptake in the liver and blood than that observed for [¹²⁵I]MIP-1095. [^125/131I]23b may serve as an optimal PSMA ligand for radiotherapy treatment of prostate cancer over-expressing PSMA.     

Synthesis and in vitro evaluation of radioiodinated indolequinones targeting NAD(P)H: Quinone oxidoreductase 1 for internal radiation therapy

NAD(P)H: quinone oxidoreductase 1 (NQO1) is an obligate two-electron reductase and is highly expressed in many human solid cancers. Because NQO1 can be induced immediately after exposure to ionizing radiation, we aimed to develop an NQO1-targeted radiolabeled agent to establish a novel internal radiation therapy that amplifies the therapeutic effects when combined with external radiation therapy. We designed three NQO1-targeted radioiodinated compounds including two ether linkage compounds ([¹²⁵I]1 and [¹²⁵I]2) and a sulfide linkage compound ([¹²⁵I]3) based on the selective binding of indolequinone analogs to the active site of NQO1 by the stacking effect. These compounds were successfully prepared using an oxidative iododestannylation reaction with high radiochemical yields and purity. In NQO1-expressing tumor cells, [¹²⁵I]1 and [¹²⁵I]2 were readily metabolized to p-[¹²⁵I]iodophenol or m-[¹²⁵I]iodophenol and [¹²⁵I]I⁻, whereas over 85% of the initial radioactivity of [¹²⁵I]3 was observed as an intact form at 1 h after incubation. The cellular uptake of [¹²⁵I]3 was significantly higher than those of [¹²⁵I]1 and [¹²⁵I]2. The uptake of [¹²⁵I]3 was specific and was dependent on the expression of NQO1. These data suggest that the novel NQO1-targeted radioiodinated compound [¹²⁵I]3 could be used as a novel internal radiation agent for the treatment of cancer.     

Ruthenium(II) carbonyl chloride complexes containing pyridine-functionalised bidentate N-heterocyclic carbenes: Synthesis, structures, and impact of the carbene ligands on catalytic activities

A series of new ruthenium(II) carbonyl chloride complexes with pyridine-functionalised N-heterocyclic carbenes [Ru(Py-NHC)(CO)₂Cl₂], [Py-NHC = 3-methyl-1-(2-pyridyl)imidazol-2-ylidene, 1 (1a and 1b); 3-methyl-1-(2-picoyl)imidazol-2-ylidene, 2 (2a and 2b); 3-methyl-1-(2-pyridyl)benzimidazolin-2-ylidene, 3 (3b); 3-methyl-1-(2-picoyl)benzimidazolin-2-ylidene, 4 (4a and 4b); 1-methyl-4-(2-pyridyl)-1,2,4-triazoline-5-ylidene, 5 (5a and 5b)] have been prepared by transmetallation from the corresponding silver carbene complexes and characterized by NMR, IR spectroscopy and elemental analysis. In these complexes with bidentate Py-NHC ligands, one CO ligand is trans to the Py ligand. In 1a, 2a, 4a, and 5a, the NHC ligand is trans to the other CO ligand, thus leaving the two Cl⁻ ligands trans to each other. In 1b, 2b, 3b, 4b, and 5b, the NHC ligands are trans to one Cl⁻ ligand, and the two Cl⁻ ligands are cis to each other. The structures for 1b, 2b, 3b and 4b have been determined by single-crystal X-ray diffraction. These complexes are efficient catalysts in the transfer hydrogenation of acetophenone and their catalytic activities are found to be influenced by electronic effect of the N-heterocyclic carbene ligands.     

X-ray crystal structure determinations of two thiourea tin(II) complexes: Diacetatobis(thiourea)tin(II) and ditin(II)tetrabromopenta(thiourea)dihydrate

The crystal structures of diacetatobis(thiourea)tin(II) (I) and ditin(II)tetrabromopenta(thiourea)dihydrate (II) have been determined by X-ray diffraction analysis. The compound I crystallizes in the monoclinic space group Pc with a = 11.932(6), b = 10.937(5), c = 21.919(8) Å, β = 96.5(1), Z = 8. The compound II crystallizes in the orthorhombic space group Pnma with a = 27.83(3), b = 16.13(4), c = 6.11(6) Å, Z = 4. In compound I the tin atom has a square pyramidal environment. It is bonded to two thiourea sulphur atoms and to two carboxylate oxygens. In the compound II there are two tin sites both with trigonal pyramidal coordination. The ¹¹⁹Sn Mössbauer data for thiourea tin(II) compounds are discussed, in terms of their crystal structures.     

Structural chemistry of lanthanidedicyclopentadienidehalides. Part 1. Two modifications of gadoliniumdicyclopentadienidebromide, [Gd(C5H5)2Br]2 and 1∞[Gd(C5H5)2Br]

The crystal structures of two modifications of gadoliniumdicyclopentadienidebromide, [Gd(C₅H₅)₂Br]₂ (I) and ¹_∞[Gd(C₅H₅)₂Br] (II) have been determined from X-ray diffraction data. I crystallizes in the [Sc(C₅H₅)₂Cl]₂-type structure, space group P2₁/c, with a=14.110(3), b=16.488(3), c= 13.765(3) Å, β=93.25(2)°, V=3197(2) ų, and D_c= 2.289 g cm⁻³ for Z=6 molecules. II crystallizes in space group P2₁/c with a=5.946(7), b=8.447(5), c=20.239(9) Å, β=90.11(4)°, V=1020(2) ų, D_c=2.392 g cm⁻³ for Z=4 formula units. The structures have been refined by full matrix least-squares techniques to conventional R factors of 0.034 for 3014 (I) and 1964 (II) reflections (with I>2σ(I)). I consists of dimers with two bromine bridges (mean GdBr 2.872 Å). II has a double chain structure with alternating juxtaposition of gadolinium and bromine atoms (GdBr 2.912 Å (once) and 3.133 Å (twice)). The arrangement of the C₅H₅ groups with regard to the metal η⁵ fashion) is nearly identical in I and II (mean GdC 2.63(1) Å (I) and 2.62(1) Å (II)). Single crystals of I and II are obtained by sublimation at different temperatures. The formation of both modifications is discussed as to its dependence on the state of the gaseous phase equilibrium [Gd(C₅H₅)₂Br]₂ ⇄ 2Gd(C₅H₅)₂Br. Obviously, I crystallizes from gaseous phase dimers while II forms from the monomers.     

Synthesis of andrographolide-related esters as insecticidal and acaricidal agents

In continuation of our program aimed at the development of natural product-based pesticidal agents, a series of andrographolide-related esters, such as 3,19-dialkyl(aryl)carbonyloxy andrographolide (3a–g), 3-alkyl(aryl)carbonyloxyandrographolide (4a–g), and 19-alkyl(aryl)carbonyloxyandrographolide (5a–g), were prepared. Their structures were well characterized by ¹H NMR, IR, optical rotation, HRMS and mp. Especially three-dimensional structures of compounds 3a, 4g, and 5g were unambiguously confirmed by single-crystal X-ray diffraction. Compounds 3a and 5a exhibited good insecticidal and acaricidal activities against Mythimna separata and Tetranychus cinnabarinus. Their structure-activity relationships were also discussed.     

Design and synthesis of novel N-sulfonyl-2-indoles that behave as 5-HT6 receptor ligands with significant selectivity for D3 over D2 receptors

All clinically-used antipsychotics display similar affinity for both D₂ (D2R) and D₃ (D3R) receptors, and they likewise act as 5-HT_2A receptor antagonists. They provide therapeutic benefit for positive symptoms, but no marked or consistent improvement in neurocognitive, social cognitive or negative symptoms. Since blockade of D₃ and 5-HT₆ (5-HT6R) receptors enhances neurocognition and social cognition, and potentially improves negative symptoms, a promising approach for improved treatment for schizophrenia would be to develop drugs that preferentially act at D3R versus D2R and likewise recognize 5-HT6R. Starting from the high affinity 5-HT6R ligands I and II, we identified compounds 11a and 14b that behave as 5-HT6R ligands with significant selectivity for D3R over D2R.     

Synthesis and biological activity of the intercalating agent 3-Acetamido-5-[123125I]iodo-6-aminoacridine

3-Acetamido-5-iodo-6-aminoacridine (3), a derivative of the known intercalating agent proflavine (3,6-diaminoacridine) (1) was synthesized, and no-carrier-added ¹²³I and ¹²⁵I labeled compounds prepared. Compound 3 was taken up by live cells and localized in the nucleus. The intracellular concentration of [¹²⁵I]3 was 7-fold greater in human prostate carcinoma (PC-3) cells than in normal Chinese hamster lung fibroblast (V-79) cells.