ABSTRACT
Using a think aloud approach during fixed perceived effort exercise is a unique method to explore the decision-making processes that guide the self-regulation of perceived effort during endurance-based activity. In a two-part study, authors investigated the attentional focus and self-regulatory strategies associated with: Part A - perceived effort corresponding to (RPEGET) and above gas exchange threshold (RPE+15%GET); Part B - between experienced and inexperienced cyclists during fixed perceived effort cycling tasks. Eighteen (15 male, 3 female) healthy, active individuals completed three visits (visit 1 - ramped incremental test and familiarisation, visit 2 and 3-30-min fixed perceived effort cycling). During which, power output, heart rate, lactate, think aloud, and perceptual markers were taken. Random-intercepts linear mixed-effects models assessed the condition, time, and condition × time interactions on all dependent variables. Power output, heart rate, lactate and instances of internal sensory monitoring (t195=2.57,p=.011,ß=0.95[0.23,1.68]) and self-regulation (t195=4.14,p=.001,ß=1.69[0.89,2.49]) were significantly higher in the RPE+15%GET versus RPEGET trial. No significant differences between inexperienced and experienced cyclists for internal sensory monitoring (t196=-1.78,p=.095,ß=-1.73[-3.64,0.18]) or self-regulatory thoughts (t196=-0.39,p=.699,ß=-1.06[-6.32,4.21]) were noted but there were significant condition × time interactions for internal monitoring (t196=2.02,p=.045,ß=0.44[0.01,0.87]) and self-regulation (t196=3.45,p=.001,ß=0.85[0.37,1.33]). Seemingly, experienced athletes associatively attended to internal psychophysiological state and subsequently self-regulate their psychophysiological state at earlier stages of exercise than inexperienced athletes. This is the first study to exhibit the differences in attentional focus and self-regulatory strategies that are activated based on perceived effort intensity and experience level in cyclists.
Subject(s)
Attention , Exercise , Humans , Male , Female , Exercise/physiology , Bicycling/physiology , Athletes , Lactic AcidABSTRACT
Cattle are subjected to routine procedures that require restraint and close contact to humans, which are both potentially aversive to the animal. Positive reinforcement training techniques may affect how animals perceive and respond to these procedures. The objectives of the current study were to describe a positive reinforcement regimen used to train cattle to stand still for a sham injection, and to assess the effects of this training on the responses to an actual injection. Eight "agency" heifers were trained, over an average of 85 ± 4.6 sessions, with positive reinforcement (i.e., animals received a grain reinforcer for desired behaviors) to enter a headlock, and they were habituated with counterconditioning and desensitization to a sham injection (i.e., animals were gradually exposed to the sensation of the sham injection, paired with access to grain). The headlock remained open at all times to allow heifers to leave. Eight "habituation" heifers were exposed to the treatment area and headlock for an equal number of sessions and duration as agency heifers, and 7 "naïve" heifers were provided no exposure to the treatment area. Once agency heifers tolerated the sham injection, all animals received a 1-mL subcutaneous injection of 0.9% NaCl while in the head lock (habituation and naïve heifers were locked in but agency heifers were free to withdraw). Immediate responses to the injection, starting with tenting of the skin, were video recorded and summarized as a reactivity score, which included the number of steps, head tosses, and backing-up movements; we also recorded the latency to approach the treatment area and headlock for 3 d after the injection. Of the agency heifers, 5 remained standing for the actual injection, whereas 3 heifers moved out of the headlock for a brief period (1, 3, and 5 s, respectively). Habituation heifers had a higher reactivity score [17.5 (10.5-28); median (IQR)] than agency [6 (2-13.5)] and naïve heifers [6 (5-7)]. Averaged over the 3 d after injection, agency heifers showed lower latencies to come to the treatment area [8.7 (7.2-24.2) s] than did habituation [50.5 (28-60) s] and naïve [53.7 (18-60) s] heifers. Agency heifers voluntarily entered the headlock within 1.3 (1-1.5) s but, with one exception, none of the other heifers did so within the allowed 15 s. These results indicate that dairy heifers can be trained with positive reinforcement and counterconditioning to voluntarily accept a painful procedure, and that training can reduce avoidance behaviors during and after the procedure.
Subject(s)
Avoidance Learning , Reinforcement, Psychology , Animals , Cattle , Female , Injections, Subcutaneous/veterinary , Pain/veterinaryABSTRACT
Li2TiO3/Ni foam composites were prepared by a solid-state reaction process. They crystallized in the monoclinic Li2TiO3 structure with C2/c space group. SEM images show that the Li2TiO3 particles are monodispersed crystallites of average size 49 nm, infused into porous scaffold Ni foam. As an anode in lithium battery, the composite delivered a discharge capacity of 153 mAh g-1 in an aqueous electrolyte and retained 95% of its initial capacity after 30 cycles. Moreover, the Li2TiO3/Ni foam composite as a negative electrode of pseudo-supercapacitor delivered a specific capacitance of 593 F g-1 and retained 95% of its initial capacitance after 1000 cycles. The enhanced capacity of Li2TiO3/Ni composite is due to porous scaffold Ni foam, which provides high conductivity to the Li2TiO3 particles and high effective surface area for redox reactions. The performance of the Li2TiO3/Ni foam as an electrode material for both lithium-ion batteries (LIBs) and supercapacitors (SCs) shows that this composite is promising for energy storage devices.
ABSTRACT
BACKGROUND: Transcranial direct current stimulation (tDCS) has been used to enhance endurance performance but its precise mechanisms and effects remain unknown. OBJECTIVE: To investigate the effect of bilateral tDCS on neuromuscular function and performance during a cycling time to task failure (TTF) test. METHODS: Twelve participants in randomized order received a placebo tDCS (SHAM) or real tDCS with two cathodes (CATHODAL) or two anodes (ANODAL) over bilateral motor cortices and the opposite electrode pair over the ipsilateral shoulders. Each session lasted 10 min and current was set at 2 mA. Neuromuscular assessment was performed before and after tDCS and was followed by a cycling time to task failure (TTF) test. Heart rate (HR), ratings of perceived exertion (RPE), leg muscle pain (PAIN) and blood lactate accumulation (ΔB[La-]) in response to the cycling TTF test were measured. RESULTS: Corticospinal excitability increased in the ANODAL condition (P < 0.001) while none of the other neuromuscular parameters showed any change. Neuromuscular parameters did not change in the SHAM and CATHODAL conditions. TTF was significantly longer in the ANODAL (P = 0.003) compared to CATHODAL and SHAM conditions (12.61 ± 4.65 min; 10.61 ± 4.34 min; 10.21 ± 3.47 min respectively), with significantly lower RPE and higher ΔB[La-] (P < 0.001). No differences between conditions were found for HR (P = 0.803) and PAIN during the cycling TTF test (P = 0.305). CONCLUSION: Our findings demonstrate that tDCS with the anode over both motor cortices using a bilateral extracephalic reference improves endurance performance.
Subject(s)
Motor Cortex/physiology , Physical Endurance/physiology , Transcranial Direct Current Stimulation/methods , Adult , Female , Healthy Volunteers , Heart Rate/physiology , Humans , Lactic Acid/blood , Male , Muscle, Skeletal/physiology , Pain/physiopathology , Physical Exertion/physiology , Shoulder/physiology , Time Factors , Young AdultABSTRACT
OBJECTIVES: To investigate the effects of a Mediterranean type diet on patients with osteoarthritis (OA). PARTICIPANTS: Ninety-nine volunteers with OA (aged 31 - 90 years) completed the study (83% female). SETTING: Southeast of England, UK. DESIGN: Participants were randomly allocated to the dietary intervention (DIET, n = 50) or control (CON, n = 49). The DIET group were asked to follow a Mediterranean type diet for 16 weeks whereas the CON group were asked to follow their normal diet. MEASUREMENTS: All participants completed an Arthritis Impact Measurement Scale (AIMS2) pre-, mid- and post- study period. A subset of participants attended a clinic at the start and end of the study for assessment of joint range of motion, ROM (DIET = 33, CON = 28), and to provide blood samples (DIET = 29, CON = 25) for biomarker analysis (including serum cartilage oligomeric matrix protein (sCOMP) (a marker of cartilage degradation) and a panel of other relevant biomarkers including pro- and anti-inflammatory cytokines). RESULTS: There were no differences between groups in the response of any AIMS2 components and most biomarkers (p > 0.05), except the pro-inflammatory cytokine IL-1α, which decreased in the DIET group (~47%, p = 0.010). sCOMP decreased in the DIET group by 1 U/L (~8%, p = 0.014). There was a significant improvement in knee flexion and hip rotation ROM in the DIET group (p < 0.05). CONCLUSIONS: The average reduction in sCOMP in the DIET group (1 U/L) represents a meaningful change, but the longer term effects require further study.
Subject(s)
Cartilage Oligomeric Matrix Protein/blood , Cartilage/pathology , Diet, Mediterranean , Osteoarthritis/diet therapy , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Female , Hip , Hip Joint , Humans , Knee , Knee Joint , Male , Middle Aged , Osteoarthritis/blood , Osteoarthritis/pathology , Osteoarthritis, Hip/blood , Osteoarthritis, Hip/diet therapy , Osteoarthritis, Hip/pathology , Osteoarthritis, Knee/blood , Osteoarthritis, Knee/diet therapy , Osteoarthritis, Knee/pathology , Range of Motion, ArticularABSTRACT
To compare the predictive capacity of experimental pain and exercised-induced pain (EIP) on exercise performance. Thirty-two recreationally active male (n = 23) and female (n = 9) participants were recruited. Participants completed measures of pain tolerance by cold pressor test (CPT), pain pressure threshold via algometry (PPT), and EIP tolerance using an RPE clamp trial. A VO2max test provided traditional predictors of performance [VO2max , gas-exchange threshold (GET), peak power output (PPO)]. Finally, participants completed a 16.1-km cycling time trial (TT). No correlation was found between experimental pain measures (CPT, PPT) and TT performance. However, there was a significant correlation between EIP tolerance and TT performance (R = -0.83, P < 0.01). Regression analysis for pain and physiological predictor variables (mean pain in CPT, PPT, EIP tolerance, VO2max , PPO, GET) revealed that a significant model (P < 0.01) emerged when only PPO (Adjusted R2 = 0.739) and EIP tolerance (ΔR2 = 0.075) were used to predict TT performance. These findings suggest that EIP tolerance is an important factor in endurance performance. However, PPT and CPT have limited ability to assess this relationship, and so their use in EIP research should be treated with caution.
Subject(s)
Athletic Performance , Bicycling , Exercise , Oxygen Consumption , Pain , Physical Exertion , Adult , Female , Humans , Linear Models , Male , Pain Threshold , Young AdultABSTRACT
Transcranial direct current stimulation (tDCS) can increase cortical excitability of a targeted brain area, which may affect endurance exercise performance. However, optimal electrode placement for tDCS remains unclear. We tested the effect of two different tDCS electrode montages for improving exercise performance. Nine subjects underwent a control (CON), placebo (SHAM) and two different tDCS montage sessions in a randomized design. In one tDCS session, the anodal electrode was placed over the left motor cortex and the cathodal on contralateral forehead (HEAD), while for the other montage the anodal electrode was placed over the left motor cortex and cathodal electrode above the shoulder (SHOULDER). tDCS was delivered for 10min at 2.0mA, after which participants performed an isometric time to exhaustion (TTE) test of the right knee extensors. Peripheral and central neuromuscular parameters were assessed at baseline, after tDCS application and after TTE. Heart rate (HR), ratings of perceived exertion (RPE), and leg muscle exercise-induced muscle pain (PAIN) were monitored during the TTE. TTE was longer and RPE lower in the SHOULDER condition (P<0.05). Central and peripheral parameters, and HR and PAIN did not present any differences between conditions after tDCS stimulation (P>0.05). In all conditions maximal voluntary contraction (MVC) significantly decreased after the TTE (P<0.05) while motor-evoked potential area (MEP) increased after TTE (P<0.05). These findings demonstrate that SHOULDER montage is more effective than HEAD montage to improve endurance performance, likely through avoiding the negative effects of the cathode on excitability.
Subject(s)
Isometric Contraction/physiology , Leg/physiology , Muscle Fatigue/physiology , Muscle, Skeletal/physiology , Transcranial Magnetic Stimulation , Electric Stimulation , Evoked Potentials, Motor/physiology , Femoral Nerve/physiology , Functional Laterality , Heart Rate/physiology , Humans , Male , Motor Cortex/physiology , Perception/physiology , Prefrontal Cortex/physiology , Random Allocation , Shoulder/physiology , Single-Blind Method , Transcranial Magnetic Stimulation/methods , Young AdultABSTRACT
The self-paced maximal oxygen uptake (VO2max) test (SPV), which is based on the Borg 6-20 Ratings of Perceived Exertion (RPE) scale, allows participants to self-regulate their exercise intensity during a closed-loop incremental maximal exercise test. As previous research has assessed the utility of the SPV test within laboratory conditions, the purpose to this study was to assess the effect of trial familiarisation on the validity and reproducibility of a field-based, SPV test. In a cross-sectional study, fifteen men completed one laboratory-based graded exercise test (GXT) and three field-based SPV tests. The GXT was continuous and incremental until the attainment of VO2max. The SPV, which was completed on an outdoor 400m athletic track, consisted of five x 2 min perceptually-regulated (RPE11, 13, 15, 17 and 20) stages of incremental exercise. There were no differences in the VO2max reported between the GXT (63.5±10.1 ml·kg(-1)·min(-1)) and each SPV test (65.5±8.7, 65.4±7.0 and 66.7±7.7 ml·kg(-1)·min(-1) for SPV1, SPV2 and SPV3, respectively; P>.05). Similar findings were observed when comparing VO2max between SPV tests (P>.05). High intraclass correlation coefficients were reported between the GXT and the SPV, and between each SPV test (≥.80). Although participants ran faster and further during SPV3, a similar pacing strategy was implemented during all tests. This study demonstrated that a field-based SPV is a valid and reliable VO2max test. As trial familiarisation did not moderate VO2max values from the SPV, the application of a single SPV test is an appropriate stand-alone protocol for gauging VO2max.
ABSTRACT
Novel lithium metal polymer solid state batteries with nano C-LiFePO4 and nano Li1.2V3O8 counter-electrodes (average particle size 200 nm) were studied for the first time by in situ SEM and impedance during cycling. The kinetics of Li-motion during cycling is analyzed self-consistently together with the electrochemical properties. We show that the cycling life of the nano Li1.2V3O8 is limited by the dissolution of the vanadium in the electrolyte, which explains the choice of nano C-LiFePO4 (1300 cycles at 100% DOD): with this olivine, no dissolution is observed. In combination with lithium metal, at high loading and with a stable SEI an ultrahigh energy density battery was thus newly developed in our laboratory.
ABSTRACT
OBJECTIVE: To determine the importance of the provision of external exercise information to the setting of the pacing strategy, in subjects unfamiliar with a cycling task. DESIGN: Twenty-two healthy, untrained cyclists (VO(2max), 50 ± 9 mL-(1)·kg-(1)·min-(1)) were randomly assigned to a control (CON) group or an experimental (EXP) group and two successive 4 km time trials (TT) were performed, separated by a 17 min recovery. The CON group received distance knowledge and distance feedback; the EXP group received neither, but knew that each TT was to be of the same distance. RESULTS: No significant difference in completion time (p>0.05) was observed between the groups for either time to complete TT one (TT1) (CON=443 ± 33 s versus EXP=471 ± 63 s) or time to complete TT two (time trial 2) (CON=461 ± 37 s versus EXP=501 ± 94 s). No significant difference in the final RPE was observed between groups. However, a significant interaction for RPE (rating of perceived exertion)×TT in the CON was observed (F7,70=5.32, p<0.05), with significantly higher RPE values in the final kilometre of TT2 (p<0.05). CONCLUSION: The lack of any performance improvement in either group, despite the differences in exercise information received, indicates both a reliance on the afferent feedback for setting a pacing strategy and slow learning effect from practice in subjects unfamiliar with the task. The modification in RPE profile observed in the CON, despite no performance improvement, suggests exercise perception based changes may pre-empt work rate based changes and thus not immediately translate to improved performance.
Subject(s)
Athletic Performance/physiology , Bicycling/physiology , Exercise/physiology , Analysis of Variance , Energy Metabolism/physiology , Feedback , Heart Rate/physiology , Humans , Male , Oxygen Consumption/physiology , Time Factors , Young AdultABSTRACT
OBJECTIVE: To determine whether the provision of comparative performance feedback during 4 km track cycling affects completion time. DESIGN: Five highly trained male cyclists first performed a baseline (BL) 4-km time trial (TT) on a velodrome track, followed by two further randomised 4-km TT, during which riders received either correct (COR) or non-contingent (FAL) feedback based on their BL performance. RESULTS: Participants completed the COR TT in a significantly faster time (t(4)=-3.10, p<0.05) than the FAL TT (341 (8) s vs 350 (12) s). Over the TT, a significant difference in mean speed was apparent between the two conditions (F(15,60)=1.95, p<0.05) on the second (t(4)=4.71, p<0.05), 15th (t(4)=3.45, p<0.05) and final lap (t(4)=3.30, p<0.05). CONCLUSION: The significant difference in completion time and pacing strategy between the two conditions suggests that accurate, comparative performance feedback is beneficial to performance, especially during the start and end of an exercise bout. The results support the previously unfounded assumption that performance feedback is advantageous during exercise and highlights the importance of an athlete's support team during an event.
Subject(s)
Athletic Performance/physiology , Bicycling/physiology , Feedback, Physiological/physiology , Analysis of Variance , Humans , Male , Middle AgedABSTRACT
We report on the use of magnetic sedimentation as a means to determine the size distribution of dispersed magnetic particles. The particles investigated here are (i) single anionic and cationic nanoparticles of diameter D approximately 7 nm and (ii) nanoparticle clusters resulting from electrostatic complexation with polyelectrolytes and polyelectrolyte-neutral copolymers. A theoretical expression of the sedimentation concentration profiles at the steady state is proposed, and it is found to accurately describe the experimental data. When compared to dynamic light scattering, vibrating sample magnetometry, and cryogenic transmission electron microscopy, magnetic sedimentation exhibits a unique property: it provides the core size and core size distribution of nanoparticle aggregates.
Subject(s)
Chemistry, Physical/methods , Magnetics , Nanoparticles/chemistry , Nanotechnology/methods , Anions , Cations , Light , Microscopy, Electron, Transmission , Models, Statistical , Nanostructures , Particle Size , Polymers/chemistry , Scattering, Radiation , Static Electricity , Surface PropertiesABSTRACT
The essential structural features of lithium-metal phosphates (LMP) have been studied using FTIR spectroscopy which is a sensitive tool to probe the local environment in the solid materials. Various LMP materials where M is iron have been investigated including phospho-olivine LiFePO(4), diphosphate LiFeP(2)O(7), Nasicon-type phosphate Li(3)Fe(2)(PO(4))(3) and dihydrate FePO(4).2H(2)O. Vitreous and amorphous materials are also considered. Analysis of internal and external modes of vibration allows to distinguish between the different phases and the type of cationic environment in the framework. Results corroborate the contribution of the main factors which are responsible for the complexity of the spectra, i.e. departure from ideal symmetry, interactions between polyhedra, bridging atoms and lattice distortion.
Subject(s)
Diphosphates/chemistry , Electric Power Supplies , Ferric Compounds/chemistry , Ferrous Compounds/chemistry , Iron Compounds/chemistry , Lithium Compounds/chemistry , Phosphates/chemistry , Spectroscopy, Fourier Transform Infrared/methods , Electrodes , Equipment Reuse , Iron/chemistry , Lithium/chemistry , Magnesium Compounds/chemistry , Silicates/chemistry , Spectrum AnalysisABSTRACT
We report on a possible crossover of a nonuniversal quantity at the upper critical dimensionality in the field of percolation. Plotting recent estimates for site percolation thresholds of hypercubes in dimension 6 < or =d < or =13 against corresponding predictions from the Galam-Mauger (GM) formula p(c) = p(0) [(d-1) (q-1)](-a) d(b) for percolation thresholds, a significant departure of p(c) is observed for d > or =6 . This result is reminiscent of the crossover undergone by universal quantities in critical phenomena. For bond percolation, evidence of such a crossover of dimensionality would require an improvement of the GM formula to reach a relative error of typically 0.2%, while it is currently at 0.9% for hypercubes.
ABSTRACT
Fluorinated 2-phenyl-4-quinolone derivatives were synthesized and evaluated in National Cancer Institute's 60 human tumor cell line in vitro screen. From the results, the ketone moiety plays an essential role in activity. Among the compounds tested, 2'-fluoro-6-pyrrol-2-phenyl-4-quinolone (13) exhibited the most potent cytotoxic activities (log GI(50) < -8.00) against renal and melanoma tumor cell lines. Compound 13 was also a potent inhibitor of tubulin polymerization (IC(50) = 0.46 microM) and of radiolabeled colchicine binding to tubulin, with activities comparable to those of the potent antimitotic natural products colchicine, podophyllotoxin, and combretastatin A-4.
Subject(s)
Antineoplastic Agents/chemical synthesis , Pyrroles/chemical synthesis , Quinolones/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Biopolymers , Drug Screening Assays, Antitumor , Humans , Mitosis/drug effects , Pyrroles/chemistry , Pyrroles/pharmacology , Quinolones/chemistry , Quinolones/pharmacology , Structure-Activity Relationship , Tubulin/chemistry , Tumor Cells, CulturedABSTRACT
Structure elucidation of five components of the actinomycin Z complex (Z(1)-Z(5)) isolated from Streptomyces fradiae is described. The components were separated by Si gel column chromatography and TLC/PLC and analyzed by ESIMS, FABMS, LC-MS of derivatized hydrolysates, and 2D NMR techniques. This permitted determination of the complete structures of actinomycins Z(1)-Z(5). In Z(3) and Z(5,) site 1 of the beta-depsipeptide is occupied by the rare 4-chloro-L-threonine, an amino acid not previously found in an actinomycin. The structural variants of the actinomycin Z complex have the molecular architecture typical of other actinomycins but possess greater structural diversity resulting from the presence of several highly unusual amino acids. Actinomycins Z(3) and Z(5,) but not Z(1), were more potent than actinomycin D in cytotoxicity assays against three tumor cell lines.
Subject(s)
Antibiotics, Antineoplastic/chemistry , Dactinomycin/chemistry , Streptomyces/chemistry , Threonine/analogs & derivatives , Antibiotics, Antineoplastic/pharmacology , Dactinomycin/analogs & derivatives , Dactinomycin/pharmacology , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Spectrum Analysis , Threonine/chemistry , Tumor Cells, CulturedABSTRACT
As part of our continuing search for potential anticancer drug candidates in the 2-aryl-1,8-naphthyridin-4-one series, we have synthesized a series of substituted 2-thienyl-1, 8-naphthyridin-4-ones. Most compounds showed significant cytotoxic effects (log GI(50) < -4.0; log molar drug concentration required to cause 50% growth inhibition) against a variety of human tumor cell lines in the National Cancer Institute's in vitro screen, including cells derived from solid tumors such as non-small-cell lung, colon, central nervous system, melanoma, ovarian, prostate, and breast cancers. The most active compounds (31-33,40) demonstrated strong cytotoxic effects with ED(50) values in the micromolar or submicromolar range in most of the tumor cell lines. The most cytotoxic compounds inhibited tubulin polymerization at concentrations substoichiometric to the tubulin concentration. The most potent inhibitors of polymerization (40,42,43) had effects comparable to those of the potent antimitotic natural products podophyllotoxin and combretastatin A-4 and to that of NSC 664171, a particularly potent, structurally related analogue. Only compound 40 was a potent inhibitor of the binding of radiolabeled colchicine to tubulin, and it was both the most cytotoxic agent and the most effective inhibitor of polymerization among the newly synthesized compounds.
Subject(s)
Antineoplastic Agents/chemical synthesis , Naphthyridines/chemical synthesis , Thiophenes/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Biopolymers , Colchicine/chemistry , Drug Screening Assays, Antitumor , Humans , Inhibitory Concentration 50 , Models, Molecular , Naphthyridines/chemistry , Naphthyridines/pharmacology , Structure-Activity Relationship , Thiophenes/chemistry , Thiophenes/pharmacology , Tubulin/chemistry , Tumor Cells, CulturedABSTRACT
2- and 3-Methyl-4,8-dihydrobenzo[1,2-b:5,4-b']dithiophene-4,8-dione and related derivatives were synthesized and evaluated in vitro by NCI against eight cancer types. Compounds 12-15 showed significant activity against melanoma, NCI-H23 non-small cell lung cancer, and MDA-MB-435 and MDA-N breast cancer cell lines; 2-hydroxymethyl-4,8-dihydrobenzo[1,2-b:5,4-b']dithiophene-4,8-dion e (13) showed the highest activity against melanoma (mean log GI50 = -7.74) and the highest overall potency (mean log GI50 = -6.99).
Subject(s)
Antineoplastic Agents/chemical synthesis , Thiophenes/chemical synthesis , Antineoplastic Agents/pharmacology , Drug Screening Assays, Antitumor , Humans , Thiophenes/pharmacology , Tumor Cells, CulturedABSTRACT
Four new cytotoxic 8,9-secokauranes have been identified from the liverwort Lepidolaena taylorii. The 11-oxygenation found in three of these has not been encountered in the 8,9-secokauranes known from higher plants. NMR studies were combined with molecular modelling to determine the preferred conformations. Six structurally related kauren-15-ones were also found, including three new compounds. Some of these compounds showed differential cytotoxic activity against human tumor cell lines. The probable mode of cytotoxic action was supported by Michael addition of a thiol. Two 8,9-secokauranes were the main cytotoxins in another New Zealand liverwort. L. palpebrifolia.