Determination of the maximum and minimum lethal temperatures (LT50) for Loxosceles intermedia Mello-Leitão, 1934 and L. laeta (Nicolet, 1849) (Araneae, Sicariidae)

In this study, the maximum and minimum lethal temperatures (LT₅₀) of L. intermedia and L. laeta were determined in two treatments: gradual heating (25–50°C) and cooling (25°C to −5°C), and 1 h at a constant temperature. In gradual temperatures change, L. intermedia mortality started at 40°C and the LT₅₀ was 42°C; for L. laeta, mortality began at 35°C and the LT₅₀ was 40°C. At low temperatures, mortality was registered only at −5°C for both species. In the constant temperature L. intermedia showed a maximum LT₅₀ at 35°C and L. laeta at 32°C; the minimum LT for both species was −7°C.     

In vitro antiprotozoal activity of the lipophilic extracts of different parts of Turkish Pistacia vera L.

Thirteen lipophilic extracts prepared with n-hexane from various parts of Pistacia vera L. tree (Anacardiaceae) growing in Turkey were screened for their in vitro activity against four parasitic protozoa, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Plasmodium falciparum. Melarsoprol, benznidazole, miltefosine, artemisinin and chloroquine were used as reference drugs. The cytotoxic potentials of the extracts on rat skeletal myoblast (L6) cells were also assessed and compared to that of podophyllotoxin. The screening method employed was medium-throughput, where the extracts were tested at two concentrations, at 0.8 and 4.8 μg/ml (T. brucei rhodesiense, L. donovani and Plasmodium falciparum), or at 1.6 and 9.7 μg/ml (T. cruzi and L6 cells). At 4.8 μg/ml concentration, the branch extract of Pistacia vera (PV-BR) significantly inhibited (77.3%) the growth of L. donovani, whereas the dry leaf extract (PV-DL) was active against Plasmodium falciparum (60.6% inhibition). The IC₅₀ values of these extracts were determined as 2.3 μg/ml (PV-BR, L. donovani) and 3.65 μg/ml (PV-DL, Plasmodium falciparum). None of the extracts possessed cytotoxicity on mammalian cells.     

Structural determinations, magnetic and EPR studies of complexes involving the Cr(OH)2Cr unit

Five heterometallic compounds with formulae [Ba(H₂O)₄Cr₂(μ-OH)₂(nta)₂] · 3H₂O (I), [M(bpy)₂(H₂O)₂] [Cr₂(OH)₂(nta)₂] · 7H₂O, where M²⁺ = Zn, (II); Ni, (III); Co, (IV) and [Mn(H₂O)₃(bpy)Cr₂(OH)₂(nta)₂] · (bpy) · 5H₂O (V); bpy = 2,2′-bipyridine, (nta = nitrilotriacetate ion) have been prepared by reaction of I with the corresponding M^II-sulfates in the presence of 2,2′-bipyridine. Substances I–V have been characterized by magnetic susceptibility measurements, EPR and X-ray determinations. I represents a 2D coordination polymer formed by coordination of centrosymmetrical dimeric chromium(III) units and Barium cations. The 10-coordinate Ba polyhedron is completed by four water molecules. Compounds II–IV are isostructural and consist of non-centrosymmetric dimeric anions [Cr₂(μ-OH)₂(nta)₂]²⁻, complex cations [M^II(bpy)₂(H₂O)₂]²⁺ and solvate water molecules. The octahedral coordination of chromium atoms implies four donor atoms of the nta³⁻ ligands and two bridging OH groups. Multiple hydrogen bonds of coordinated and solvate water molecules link anions and cations in a 3D network. A similar [Cr₂(μ-OH)₂(nta)₂]²⁻ unit is found in V. The bridging function is performed by a carboxylate oxygen atom of the nta ligand that leads to the formation of a trinuclear complex [Mn(bpy)(H₂O)₂Cr₂(μ-OH)₂(nta)₂]. Experimental and calculated frequency and temperature dependences of EPR spectra of these compounds are presented. The fine structure appearing on the EPR spectra of compound V is analyzed in detail at different temperatures. It is established that the main part of the EPR signals is due to the transitions in the spin states of a spin multiplet with S = 2. Analyses of experimental and calculated spectra confirm the absence of interaction between metal ions (M^II) and Cr-dimers in complexes III and IV and the presence of weak Mn–Cr interactions in V. The temperature dependence of magnetic susceptibilities for I–V was fitted on the basis of the expression derived from isotropic Hamiltonian including a bi-quadratic exchange term.     

Effect of leaf age on CAM activity in Littorella uniflora

In this study the effect of ontogenetic drift on crassulacean acid metabolism (CAM) was investigated in the aquatic CAM-isoetid Littorella uniflora. The results of this study strengthen the general hypothesis of CAM being a carbon-conserving mechanism in aquatic plants, because high-CAM capacity (45–183 μequiv. g⁻¹ FW) was present in all leaves of L. uniflora irrespective of age. Since possession of CAM in aquatic plants allows CO₂ uptake throughout the light/dark cycle, presence of CAM in all leaves influences the carbon balance of L. uniflora positively. On average for all lakes, different leaf classes accounted for 11–36% of the total dark CO₂ uptake by the individual plant.

The capacity for both CAM and photosynthesis declined with increasing leaf age, and was in the oldest leaves only 25–53% of the capacity in the youngest. The photosynthetic capacity was estimated to be sufficiently high to ensure refixation of the CO₂ released from malate during decarboxylation in the daytime. In line with this, a linear coupling between CAM capacity and photosynthetic capacity was found. Parallel to the change in photosynthetic capacity, an age-related change in total ribulose-bisphosphate carboxylase/oxygenase (rubisco) activity from 732 μmol C g⁻¹ DW h⁻¹ in the youngest leaves to 346 μmol C g⁻¹ DW h⁻¹ in the oldest was observed. In contrast, no significant change in phosphoenolpyruvate carboxylase (PEPcase) activity with leaf age was observed (means ranged between 46 and 156 μmol C g⁻¹ DW h⁻¹).     

Loss of caveolin-1 expression is associated with disruption of muscarinic cholinergic activities in the urinary bladder

Caveolin-1 (Cav1), a structural protein of caveolae, plays cell- and context-dependent roles in signal transduction pathway regulation. We have generated a knockout mouse homozygous for a null mutation of the Cav1 gene. Cav1 knockout mice exhibited impaired urinary bladder contractions in vivo during cystometry. Contractions of male bladder strips were evoked with electric and pharmacologic stimulation (5–40 Hz, 1–10 μM carbachol, 10 mM ,β-methylene ATP, 100 mM KCl). Acetylcholine (ACh) and norepinephrine (NE) release from bladder strips were measured with a radiochemical method by incubating the strips with ¹⁴C-choline and ³H-NE prior to electric stimulation, whereas ATP release was measured using the luciferin-luciferase assay with a luminometer. A 60–75% decline in contractility was observed when Cav1 knockout muscle strips were stimulated with electric current or carbachol, compared to wildtype muscle strips. No difference in contractility was noted when contractions were evoked either by the purinergic agonist ,β-methylene ATP, or by extracellular potassium. To investigate the relative contribution of non-cholinergic activity to bladder contractility, the amplitude of the electric stimulation-evoked contractions was compared in the presence of the muscarinic antagonist atropine (1 μM). While the non-muscarinic (purinergic) response was unaltered, muscarinic cholinergic response was principally disrupted in Cav1 knockout mice. The loss of Cav1 gene expression was also associated with a 70% reduction in ACh release. NE and ATP release was not altered. It is concluded that the loss of caveolin-1 is associated with disruption of M₃ muscarinic cholinergic activity in the bladder. Both pre-junctional (acetylcholine neurotransmitter release from neuromuscular junctions) and post-junctional (M₃ receptor-mediated signal transduction in bladder smooth muscles) mechanisms are disrupted, resulting in impaired bladder contraction.     

Synthesis and in vitro evaluation of leishmanicidal and trypanocidal activities of N-quinolin-8-yl-arylsulfonamides

In the present paper 12 N-quinolin-8-yl-arylsulfonamides synthesized by coupling 8-aminoquinolines with various arylsulfonylchlorides were assayed in vitro against Leishmania amazonensis, Leishmania chagasi and Trypanosoma cruzi strains. This series of new compounds were found to be selective for Leishmania spp. promastigote and amastigote forms. The most active compound was the N-(8-quinolyl)-3,5-difluoro-benzenesulfonamide 10 with an IC₅₀ against L. amazonensis and L. chagasi of 2.12 and 0.45 μM, respectively. The less cytotoxic biphenyl derivative 7 was very effective against intracellular L. amazonensis with a reduction of macrophage cell infection of 82.1% at 25 μM. In addition, a copper complex 17 of an inactive ligand was readily synthesized and showed high leishmanicidal and trypanocidal activity against both extra and intracellular forms.     

Relationship between tomato fruit growth and fruit osmotic potential under salinity

To investigate the relationship between fruit growth and fruit osmotic potential (Ψ_s) in salty conditions, a sensitive tomato cultivar (Lycopersicon esculentum Mill.) and a tolerant accession of the wild species Lycopersicon pimpinellifolium Mill. were grown in a greenhouse with 0 and 70 mM NaCl, and the growth of the fruit studied from 15 to 70 days after anthesis (DAA). L. pimpinellifolium did not reduce significantly fruit weight in salty conditions throughout the growth period, whereas L. esculentum fruit weights decreased significantly with salinity from 45 DAA. L. esculentum fruit fresh weight reductions resulted from both less dry matter and water accumulation, although the fruit water content was affected by salinity before the fruit weight. In both species, fruit osmotic potential (Ψ_s) decreased significantly with salinity during the rapid fruit growth phase, although the changes were different. Thus, fruits from L. pimpinellifolium salt treated plants showed a Ψ_s reduction at the beginning (15 DAA) twice as high as that found in L. esculentum. As the advanced growth stage (from 15 to 55 DAA), the Ψ_s reduction percentages induced by salinity were quite similar in L. pimpinellifolium fruits, while increased in L. esculentum. Under saline conditions, the solutes contributing to reduce the fruit Ψ_s during the first 55 DAA were the inorganic solutes in both species, while in the ripe fruits they were hexoses. L. esculentum fruits accumulated K⁺ as the main osmoticum in salty conditions, while L. pimpinellifolium fruits were able to use not only K⁺ but also the Na⁺ provided by the salt.     

Novel oxotremorine-related heterocyclic derivatives: Synthesis and in vitro pharmacology at the muscarinic receptor subtypes

A set of novel heterocyclic ligands (6–27) structurally related to Oxotremorine 2 was designed, synthesized and tested at muscarinic receptor subtypes (mAChRs). In the binding experiments at cloned human receptors (hm1–5), compounds 7 and 15 evidenced a remarkable affinity and selectivity for the hm2 subtype. The in vitro functional assays, performed on a selected group of derivatives at M₁, M₂, and M₃ tissue preparations, singled out the 3-butynyloxy-5-methylisoxazole trimethylammonium salt 7 as a potent unselective muscarinic agonist [pEC₅₀: 7.40 (M₁), 8.18 (M₂), and 8.14 (M₃)], whereas its 5-phenyl analogue 12 behaved as a muscarinic antagonist, slightly selective for the M₁ subtype [pK_B: 6.88 (M₁), 5.95 (M₂), 5.53 (M₃)]. Moreover, the functional data put in evidence that the presence of the piperidine ring may generate a functional selectivity, e.g., an M₁ antagonist/M₂ partial agonist/M₃ full agonist profile (compound 21), at variance with the corresponding quaternary ammonium salt (compound 22) which behaved as a muscarinic agonist at all M_1–3 receptors, with an appreciable selectivity for the cardiac M₂ receptors.     

Effects of tannic acid and its related compounds on food mutagens or hydrogen peroxide-induced DNA strands breaks in human lymphocytes

The effect of tannic acid (TA), gallic acid (GA), propyl gallate (PA) and ellagic acid (EA) on DNA damage in human lymphocytes induced by food mutagens [3-amino-1-methyl-5H-pyrido (4,3-b) indole (Trp-P-2) and 2-amino-1-methyl-6-phenylimadazo (4,5-b) pyridine (PhIP) or H₂O₂ was evaluated by using single-cell electrophoresis (comet assay). The toxicity of these tested compounds (0.1–100 μg/ml) on lymphocytes was not found. These compounds did not cause DNA strand breaks at lower concentrations of 0.1–10 μg/ml. At a concentration of 100 μg/ml, TA and GA exhibited slight DNA damage, whereas PA and EA showed no DNA strand breaks. TA and its related compounds decreased the DNA strand breaks induced by Trp-P-2, PhIP or H₂O₂ at concentrations of 0.1–10 μg/ml. DNA repair enzymes endonuclease III (Endo III) and formamidopyrimidine-DNA glycoslase (FPG)] were used to examine the levels of oxidised pyrimidines and purines in human lymphocytes induced by H₂O₂. All the compounds at 10 μg/ml can reduce the level of FPG sensitive sites. However, only EA inhibited the formation of EndoIII sensitive sites. The results indicated that these compounds can enhance lymphocytes resistance towards DNA strand breaks induced by food mutagens or H₂O₂ in vitro.     

Anti-proliferative lichen compounds with inhibitory activity on 12(S)-HETE production in human platelets

Several lichen compounds, i.e. lobaric acid (1), a β-orcinol depsidone from Stereocaulon alpinum L., (+)-protolichesterinic acid (2), an aliphatic -methylene-γ-lactone from Cetraria islandica Laur. (Parmeliaceae), (+)-usnic acid (3), a dibenzofuran from Cladonia arbuscula (Wallr.) Rabenh. (Cladoniaceae), parietin (4), an anthraquinone from Xanthoria elegans (Link) Th. Fr. (Calaplacaceae) and baeomycesic acid (5), a β-orcinol depside isolated from Thamnolia vermicularis (Sw.) Schaer. var. subuliformis (Ehrh.) Schaer. were tested for inhibitory activity on platelet-type 12(S)-lipoxygenase using a cell-based in vitro system in human platelets. Lobaric acid (1) and (+)-protolichesterinic acid (2) proved to be pronounced inhibitors of platelet-type 12(S)-lipoxygenase, whereas baeomycesic acid (5) showed only weak activity (inhibitory activity at a concentration of 100 μg/ml: 1 93.4±6.62%, 2 98,5±1.19%, 5 14.7±2.76%). Usnic acid (3) and parietin (4) were not active at this concentration. 1 and 2 showed a clear dose–response relationship in the range of 3.33–100 μg/ml. According to the calculated IC₅₀ values the highest inhibitory activity was observed for the depsidone 1 (IC₅₀=28.5 μM) followed by 2 (IC₅₀=77.0 μM). The activity of 1 was comparable to that of the flavone baicalein, which is known as a selective 12(S)-lipoxygenase inhibitor (IC₅₀=24.6 μM).     

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.     

Gas exchange and photosynthetic water use efficiency in response to light, CO2 concentration and temperature in Vicia faba

Light and temperature-response curves and their resulting coefficients, obtained within ecophysiological characterization of gas exchanges at the leaf level, may represent useful criteria for breeding and cultivar selection and required tools for simulation models aimed at the prediction of potential plant behaviour in response to environmental conditions.

Leaf-scale gas exchanges, by means of an IRGA open-flow system, were measured in response to light intensity (8 levels from 0 up to 2000 μmol m⁻² s⁻¹), CO₂ concentrations (ambient—350 μmol mol⁻¹ and short-term enriched—700 μmol mol⁻¹) and air temperature (from 7 up to 35 °C) on three Vicia faba L. genotypes, each representing one of the three cultivated groups: major, equina and minor. The net assimilation rate response to light intensity was well described by an exponential rise to max function. The short-term CO₂ enrichment markedly increased the values of light response curve parameters such as maximum photosynthetic rate (+80%), light saturation point (+40%) and quantum yield (+30%), while less homogenous behaviour was reported for dark respiration and light compensation point. For each light intensity level, the major and minor genotypes studied showed assimilation rates at least a 30% higher than equina.

The positive effects of short-term CO₂ enrichment on photosynthetic water use efficiency (WUE) indicate a relevant advantage in doubling CO₂ concentration. In the major and minor genotypes studied, similar assimilation rates, but different WUE were observed.

The optimum leaf temperature for assimilation process, calculated through a polynomial function, was 26–27 °C and no relevant limitations were observed in the range between 21 and 32 °C.

Analysis at the single leaf level provided both rapid information on the variations in gas exchange in response to environmental factors and selection criteria for the screening of genotypes.     

Anti-allergic substances from the rhizomes of Dioscorea membranacea

Extracts of five species of Thai medicinal plants, locally known as Hua-Khao-Yen, were screened for anti-allergic activities using RBL-2H3 cells. Of the five species studied, the ethanolic extract of Dioscorea membranacea exhibited potent inhibitory activity against β-hexosaminidase release as a marker of degranulation in RBL-2H3 cells, with an IC₅₀ value of 37.5 μg/mL. Eight compounds were isolated from this crude ethanolic extract, [two naphthofuranoxepins (1, 2), one phenanthraquinone (3), three steroids (4–6), and two steroidal saponins (7, 8)], and tested for their anti-allergic activities. The results showed that dioscorealide B (2) possessed the highest activity with an IC₅₀ value of 5.7 μM, followed by dioscoreanone (3, IC₅₀ = 7.7 μM), dioscorealide A (1, IC₅₀ = 27.9 μM), and diosgenin (9, IC₅₀ = 29.9 μM). Structure–activity relationship studies of naphthofuranoxepins on anti-allergic activity revealed that the hydroxylation at position 8 conferred higher activity than methoxylation. For diosgenin derivatives, the aglycone was found to possess higher activity than the diglucosylated molecule; whereas substitution with rhamnoglucosides apparently results in loss of activity. Furthermore, effects of dioscorealide A, dioscorealide B, and dioscoreanone on antigen-induced release of TNF- and IL-4 in the late phase reaction were also examined.     

In vitro excystment of the metacercaria of Plagiorchis species 1 (Trematoda, Plagiorchiidae)

1986. In vitro excystrnent of the metacercaria of Plagiorchis species 1 (Trematoda, Plagiorchiidae). International Journal for Parasitology 16: 641–645. An optimal hatching success of Plagiorchis species 1 metacercariae (100% excystment, active metacercariae, mean hatching speed 2–10 min, lowest variance of the mean speed) was observed after pretreatment in an HCl-pepsin solution at pH 2.0 and 42°C for 60–70 min, and incubation in a hatching medium at 42 °C and pH 7.3–8.0 with a bile salt (Nacholate), NaHCO₃, and a reductant (cysteine with 100% N₂). The minimum conditions for nearly 100% excystment with lower hatching speeds and higher variances were the presence of NaHCO₃, an oxygen concentration reduced to about 3% in the gas phase, pH> 7.3 and a temperature near 30°C if Na-cholate was absent, or in the presence of the bile salt, a phosphate buffer at pH> 5.0 and room temperature only. Obviously some hatching factors acted interchangeably with compensation for missing stimuli by others. The effect of the bile salt was comparable with that of other surfactants. The metacercariae excysted in nonenzymatic media, which implies an active hatching mechanism.     

Modification at the C9 position of the marine natural product isoaaptamine and the impact on HIV-1, mycobacterial, and tumor cell activity

As part of an investigation to generate optimized drug leads from marine natural pharmacophores for the treatment of neoplastic and infectious diseases, a series of novel isoaaptamine analogs were prepared by coupling acyl halides to the C9 position of isoaaptamine (2) isolated from the Aaptos sponge. This library of new semisynthetic products was evaluated for biological activity against HIV-1, Mtb, AIDS-OI, tropical parasitic diseases, and cancer. Compound 4 showed potent activity against HIV-1 (EC₅₀ 0.47 μg/mL), compound 19 proved to possess remarkable activity against Mycobacterium intracellulare with an IC₅₀ and MIC value of 0.15 and 0.31 μg/mL, while compounds 4 and 17 possessed anti-leishmanial activity with IC₅₀ values of 0.1 and 0.4 μg/mL, respectively. Compounds 16 and 17 showed antimalarial activity with EC₅₀ values of 230 and 240 ng/mL, respectively, and compound 14 exhibited an EC₅₀ of 0.05 μM against the Leukemia cell line K-562.     

In vitro antiplasmodial activity of extract and constituents from Esenbeckia febrifuga, a plant traditionally used to treat malaria in the Brazilian Amazon

Esenbeckia febrifuga (Rutaceae) is a plant traditionally used to treat malaria in the Brazilian Amazon region. Ethanol extract of stems displayed a good antiplasmodial activity against Plasmodium falciparum strains W-2 (IC₅₀ 15.5±0.71 μg/ml) and 3 D7 (IC₅₀ 21.0±1.4 μg/ml). Two coumarins (bergaptene 1 and isopimpinellin 2), five alkaloids (flindersiamine 3, kokusaginine 4, skimmiamine 5, γ-fagarine 6 and 1-hydroxy-3-methoxy-N-methylacridone, 7), besides a limonoid (rutaevine 8), have been isolated for the first time from this species. Antiplasmodial activity of compounds 3, 5–8 has been evaluated in vitro against P. falciparum strains (W-2 and 3D7) and the furoquinolines 5 and 6 were the most potent displaying IC₅₀ values <50 μg/ml; flindersiamine (3) showed a weak activity while alkaloid 7 and rutaevine (8) were inactive (IC₅₀>100 μg/ml).     

An unexpected ‘4+2’ [N3S]/[NS] rhenium(IV) complex formed upon cleavage of a Re(V) imido bond

The reaction of [Re(NMe)Cl₃(PPh₃)₂] with the pentadentate [N₃S₂] ligand pyN₂H₂S₂---H₂ [2,6-bis(2-mercaptophenylamino)dimethylpyridine] (1) in the presence of triethylamine did not yield the anticipated six-coordinate complex [Re(NMe)(η⁵-pyN₂HS₂)] (2), but rather resulted in cleavage of the Re(V)=NMe bond. A novel six-coordinate Re(IV) [N₃S]/[NS] complex [Re(η⁴-SC₆H₄---2-NCH₂---C₅H₃N---C=NC₆H₄---2-S)(η²-NHC₆H₄---2-S)] (4) was thus obtained with the simultaneous coordination of 2-aminothiophenol, a dianionic bidentate [NS] donor resulting from the decomposition of the parent ligand and ligand 3, a dianionic tetradentate [N₃S] donor formed by partial self-condensation and subsequent oxidation of the parent ligand 1. Crystal data for 4: C₂₅H₁₈N₄S₃Re·CH₂Cl₂, monoclinic, space group P2₁/n, a=9.255(2) Å, b=11.181(2) Å, c=25.316(4) Å, β=97.434(3)°, V=2587.8(7) Å³ and Z=4.     

Crystallographic and NMR studies of antiinfective tricyclic guanidine alkaloids from the sponge Monanchora unguifera

Three tricyclic guanidine alkaloids, including 1,8a;8b,3a-didehydro-8β-hydroxyptilocaulin (1), 1,8a;8b,3a-didehydro-8-hydroxyptilocaulin (2) and mirabilin B (3), were identified from the marine sponge Monanchora unguifera. 1,8a;8b,3a-Didehydro-8-hydroxyptilocaulin (2) is a new stereoisomer of 1, the structure of which was elucidated by spectroscopic analysis, comparison of its spectral data with those of 1, and confirmed by X-ray analysis. Compounds 1 and 2 co-crystallized in an unusual perfect order and packed around an approximate inversion center. A mixture of 1 and 2 is active against the malaria parasite Plasmodium falciparum with an IC₅₀ value of 3.8 μg/mL while mirabilin B (3) exhibited antifungal activity against Cryptococcus neoformans with an IC₅₀ value of 7.0 μg/mL and antiprotozoal activity against Leishmania donovani with an IC₅₀ value of 17 μg/mL.