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《Bioorganic & medicinal chemistry》2020,28(22):115739
N-phenyl ureidobenzenesulfonates (PUB-SOs) is a new class of promising anticancer agents inducing replication stresses and cell cycle arrest in S-phase. However, the pharmacological target of PUB-SOs was still unidentified. Consequently, the objective of the present study was to identify and confirm the pharmacological target of the prototypical PUB-SO named 2-ethylphenyl 4-(3-ethylureido)benzenesulfonate (SFOM-0046) leading to the cell cycle arrest in S-phase. The antiproliferative and the cytotoxic activities of SFOM-0046 were characterized using the NCI-60 screening program and its fingerprint was analyzed by COMPARE algorithm. Then, human dihydroorotate dehydrogenase (hDHODH) colorimetric assay, uridine rescuing cell proliferation and molecular docking in the brequinar-binding site were performed. As a result, SFOM-0046 exhibited a mean antiproliferative activity of 3.5 μM in the NCI-60 screening program and evidenced that leukemia and colon cancer cell panels were more sensitive to SFOM-0046. COMPARE algorithm showed that the SFOM-0046 cytotoxic profile is equivalent to the ones of brequinar and dichloroallyl lawsone, two inhibitors of hDHODH. SFOM-0046 inhibited the hDHODH in the low nanomolar range (IC50 = 72 nM) and uridine rescued the cell proliferation of HT-29, HT-1080, M21 and MCF-7 cancer cell lines in the presence of SFOM-0046. Finally, molecular docking showed a binding pose of SFOM-0046 interacting with Met43 and Phe62 present in the brequinar-binding site. In conclusion, PUB-SOs and notably SFOM-0046 are new small molecules hDHODH inhibitors triggering replication stresses and S-phase arrest. 相似文献
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Communities change with time. Studying long-term change in community structure permits deeper understanding of community dynamics, and allows us to forecast community responses to perturbations at local (e.g. fire, secondary succession) and global (e.g. desertification, global warming) spatial scales. Monitoring efforts exploring the temporal dynamics of indicator taxa are therefore a critical part of conservation agendas. Here, the temporal dynamics of the Otongachi leaf litter ant community, occurring in a cloud forest in coastal Ecuador, were explored. By sampling this community six times over eleven years, I assessed how the ant fauna caught by Winkler traps (more diverse and cryptic fauna) and caught by pitfall traps (larger, more mobile fauna) changed over time. The Otongachi leaf litter ant community was dynamic. Although species richness in the community remained constant, temporal turnover of species was high: on average, 51% of the ant species in Winkler traps, and 56% of those in pitfall traps, were replaced with other ant species from one year to the other. Shifts in the rank abundance of species in the community were also large across the eleven years and, on average, shifts in the rank abundance of species collected by Winkler traps doubled those occurring in pitfall traps from one census to the other. In spite of these trends, the Otongachi ant fauna showed no (Winkler) or weak (pitfall) evidence of directional change (towards a new community). Thus, this tropical ant community can be divided in two community compartments. The Winkler compartment composed by a more diverse and cryptic ant fauna appears to be resilient and stable in time. The pitfall compartment composed by larger and more mobile ants may be prone to respond to disturbance. This study suggests that 1) species appearing/disappearing from a site may be rather the rule, difficult to separate from responses to ecological stress. 2) Conclusions made in short-term studies, or studies comparing two (e.g. before and after) snapshots of a community, should thus be revisited. Finally, 3) the ant fauna caught by pitfall traps (a rather simple and cheap survey method) is the most likely community compartment to indicate ecological perturbation. This study adds to the growing evidence that using ants as ecological indicators should incorporate long-term temporal dynamics. 相似文献
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The renin-angiotensin system (RAS) is involved in the development of left ventricular hypertrophy (LVH) by which increases cardiac morbidity and mortality. Activation of mitogen-activated protein kinases (MAPKs) and oxidative stress are important in RAS-mediated cardiac hypertrophy. Sesame oil, a potent antioxidant, attenuates hypertension-dependent LVH. We examined the protective role of sesame oil on RAS-mediated MAPK activation and oxidative stress in rats. We induced LVH using a hypertensive model by subcutaneously injecting deoxycorticosterone acetate (DOCA; 15 mg/ml/kg in mineral oil; twice weekly for 5 weeks) and supplementing with 1% sodium chloride drinking water (DOCA/salt) to uninephrectomized rats. Sesame oil was gavaged (0.5 or 1 ml/kg/day for 7 days) after 4 weeks of DOCA/salt treatment. Cardiac histopathology, RAS parameters, expression of MAPKs, reactive oxygen species and lipid peroxidation were assessed 24 h after the last dose of sesame oil. Sesame oil significantly decreased the size of cardiomyocytes and the levels of cardiac renin, angiotensin-converting enzyme and angiotensin II. In addition, sesame oil down-regulated the expression of angiotensin type 1 receptor, JNK and p38 MAPK and apoptosis signal regulating kinase 1, c-Fos and c-Jun in rats receiving DOCA/salt. Furthermore, the induction of nicotinamide adenine dinucleotide phosphate oxidase, superoxide anion and hydroxyl radical and lipid peroxidation by DOCA/salt were inhibited by sesame oil. Sesame oil modulates cardiac RAS to ameliorate LVH by inhibiting MAPK activation and lowering oxidative stress. 相似文献
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Differences in δ13C and δ15N values in stream biota are caused by several environmental conditions. Variations in abundance, species richness and the assemblage structure of stream biota are also caused by several environmental conditions. Hence, abundance, species richness and the assemblage structure of stream biota are expected to be strongly correlated with the differences in value of stable isotopes. In this study, the gaps in δ13C and δ15N between periphyton and charr are discussed in terms of the abundance, genus richness, and assemblage of benthic invertebrates at each site. Gaps in δ13C between periphyton and charr were strongly correlated with some aspects of mountainous area and the genus richness of benthic invertebrates at each site. The gaps in δ15N between periphyton and charr were strongly correlated with the abundance and assemblage structure of benthic invertebrates at the location tested. The δ13C values of predators were correlated with some aspects of mountainous area and the assemblage structure of the benthic invertebrates. The δ15N values of predators were correlated with genus richness and the assemblage structure of the benthic invertebrates. These results suggest that the value gaps in δ13C and δ15N can be used to assess biodiversity and could provide indices for estimating the biodiversity in a stream. 相似文献
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Semi-natural habitats in agricultural landscapes are generally assumed to enhance the biological control of insect pests based on native beneficial insects, by providing alternative prey and hosts, resources and refuges for overwintering. We hypothesized that natural enemies of winter wheat aphids should arrive sooner in fields near semi-natural habitats. We compared aphid, hoverfly (larvae and eggs) and parasitized aphid (mummies) abundances in 54 winter wheat fields located in southern France from 2003 to 2007. Six surveys were recorded each spring and were split into the early period (defined as the period before the peak of aphid growth) and the late period (after the peak). The wheat fields differed by their surrounding landscape composition measured as the proportion of semi-natural habitats (woods, hedges and grasslands), at three different spatial scales: 200 m, 500 m, and 1200 m. Despite great variability in abundance data between years, the abundance of hoverflies appeared more sensitive to landscape composition than aphid abundance was. Early abundance for both aphids and hoverflies was positively related to wood cover, but not late abundance in spring. The abundance of hoverflies was positively related to hedge and grassland cover at all spatial scales and both periods considered. Aphid parasitism was higher near hedges at the small spatial scale late in the spring. Our results confirmed that higher proportions of semi-natural habitats in agricultural landscapes enhance the biological control of pests, but this effect depends on the spatial scale, the time period in the spring and the natural enemies considered. 相似文献
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Major knowledge gaps exist with respect to light-quality regimes in the coastal-zone Strandzha Quercus frainetto (Q.f.) forest region adjoining the southern Bulgarian Black Sea. This paper presents preliminary results that help narrow these
gaps. In conjunction with leaf area index (LAI) field campaigns we undertook measurements with an array of 7 broad-band (ca
40 nm) sensors covering the range 0.40–0.94 μm, plus 1 sensor for UVB (0.297 μm peak) and 1 for photosynthetically active
radiation (PAR). Measurements focused on inside-forest shade conditions at sites 0 to ca 15 km from the Black Sea and at altitudes
up to ca 120 m above sea level. Some of the sites were also studied using a high-resolution spectroradiometer. A sequential
measuring strategy was necessary. This involves potentially large uncertainties, here addressed through estimations of the
variability around the sinusoidal course of daylight. Light-quality regimes were found to be in general support of earlier
studies of deciduous forests. Our data from the broad-band sensors and from the spectroradiometer are mutually supportive.
They indicate a stronger red-shift below Q.f. canopies than below canopies in enclaves dominated by Fagus orientalis and Pinus sylvestris. Transmission in the range 0.50–0.55 μm increases beneath the three types of canopies, most pronounced in the Q.f. case. Analysis of relationships between the inside-forest to open-field irradiance ratio and LAI supports the use of Beer’s
Law. We found a fairly strong relationship between the red (0.66 μm) to far-red (0.73 μm) irradiance ratios (R/FR) and LAI
for the Q.f. forest. In quantitative terms, the result is new for this Q.f. region, and suggests further research to explore whether a two-sensor approach (0.66 and 0.73 μm) might offer possibilities
for further low-cost mapping of the spatio-temporal patterns of R/FR and LAI in Strandzha. Such mapping would assist in further
studies of the region’s forest biogeochemistry and vitality. 相似文献
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