Tetrahydroindolocarbazoles (THICZs) with versatile substituents, have been designed, synthesized, structure characterized, then investigated for their in-vitro anticancer screening, urokinase inhibition (uPA) evaluated, DNA-damage determination was further explored. Compounds 5, 8, 10 and 17 displayed the most promising antitumor activities against the breast cancer cell line as compared to the standard drug, doxorubicin with IC50 = 5.24 ± 0.37, 4.00 ± 0.52, 7.20 ± 0.90 and 9.60 ± 1.10 µg/ml (versus 3.30 ± 0.48 µg/ml for doxorubicin). Compounds 5, 8, 10 and 17 represents the most significant uPA inhibitors of our study with IC50 of 3.80, 2.70. 4.75, 10.80 (ng/ml) respectively. The expression levels of CDKN2A gene were decreased in 8, 10 and 17 cell lines as compared to those in positive control samples. Cell lines treated with 5, 8, 10 and 17 clearly observed a high score of damaged DNA cells. A deeper examination revealed that our hetroaromatics showed an extensive hydrogen bonding interactions that is required in the S pocket which is important for activity Arg 217, Gly 219, Gly 216, Lys 143 and Ser 190. So we present THICZs as promising uPA inhibitors expected as significant promise for further development as anti-invasiveness drugs. 相似文献
This study investigated the olfactory responses of 3 thrips species [Frankliniella schultzei Trybom, F. occidentalis Pergrande and Thrips tabaci Lindeman (Thysanoptera: Thripidae)] to cotton seedlings [Gossypium hirsutum L. (Malvales: Malvaceae)] simultaneously damaged by different combinations of herbivores. Cotton seedlings were damaged by foliar feeding Tetranychus urticae Koch (Trombidiforms: Tetranychidae), Helicoverpa armigera Hübner (Lepidoptera: Noctuidae), Aphis gossypii Glover (Hemiptera: Aphididae) or root feeding Tenebrio molitor L. (Coleoptera: Tenebrionidae). Thrips responses to plants simultaneously damaged by 2 species of herbivore were additive and equivalent to the sum of the responses of thrips to plants damaged by single herbivore species feeding alone. For example, F. occidentalis was attracted to T. urticae damaged plants but more attracted to undamaged plants than to plants damaged by H. armigera. Plants simultaneously damaged by low densities of T. urticae and H. armigera repelled F. occidentalis but as T. urticae density increased relative to H. armigera density, F. occidentalis attraction to coinfested plants increased proportionally. Thrips tabaci did not discriminate between undamaged plants and plants damaged by H. armigera but were attracted to plants damaged by T. urticae alone or simultaneously damaged by T. urticae and H. armigera. Olfactometer assays showed that simultaneous feeding by 2 herbivores on a plant can affect predator–prey interactions. Attraction of F. occidentalis to plants damaged by its T. urticae prey was reduced when the plant was simultaneously damaged by H. armigera, T. molitor, or A. gossypii and F. schultzei was more attracted to plants simultaneously damaged by T. urticae and H. armigera than to plants damaged by T. urticae alone. We conclude that plant responses to feeding by 1 species of herbivore are affected by responses to feeding by other herbivores. These plant‐mediated interactions between herbivore complexes affect the behavioral responses of thrips which vary between species and are highly context dependent. 相似文献
Combined chemotherapy is used for the treatment of a number of malignancies such as breast cancer. The target of these antineoplastic agents is nuclear DNA, although it is not restricted to malignant cells. The aim of the present study was to assess DNA damage in peripheral blood lymphocytes (PBLs) of breast cancer patients subjected to combined adjuvant chemotherapy (5-fluorouracil, epirubicin and cyclophosphamide, FEC), using a modified comet assay to detect DNA single-strand breaks (SSB) and double-strand breaks (DSB).
Forty-one female patients with advanced breast cancer before and after chemotherapy and 60 healthy females participated in the study. Alkaline and neutral comet assays were performed in PBLs according to a standard protocol, and DNA tail moment was measured by a computer-based image analysis system.
Breast cancer patients before treatment had higher increased background levels of SSB and DSB as compared to healthy women. During treatment, a significant increase in DNA damage was observed after the 2nd cycle, which persisted until the end of treatment. Eighty days after the end of treatment the percentage of PBLs with SSB and DSB remained elevated, but the magnitude of DNA damage (tail moment) returned to baseline levels. There was no correlation between PBL DNA damage and response to chemotherapy.
DNA-SSB and DSB in PBLs are present in cancer patients before treatment and increase significantly after combined chemotherapy. No correlation with response to adjuvant chemotherapy was found. Biomonitoring DNA damage in PBLs of cancer patients could help prevent secondary effects and the potential risks of developing secondary cancers. 相似文献
Abstract: Nonlethal management alternatives are needed to minimize bird depredation of agricultural crops. We conducted 8 caged feeding tests and 2 field studies to evaluate 2 registered fungicides (GWN-4770, Gowan Company, Yuma, AZ; Quadris®, Syngenta Crop Protection, Greensboro, NC), a neem oil insecticide (Aza-Direct®, Gowan Company), and a novel terpene formulation (Gander Gone, Natural Earth Products, Winter Springs, FL) as avian repellents. For all candidate repellents, red-winged blackbirds (Agelaius phoeniceus) discriminated between untreated and treated rice during preference-testing in captivity. We observed a positive concentration-response relationship among birds offered rice treated with 2,500 ppm, 5,000 ppm, 7,500 ppm, 11,000 ppm, or 22,000 ppm GWN-4770. Relative to pretreatment, blackbirds consumed 34% and 77% less rice treated with 11,000 ppm and 22,000 ppm GWN-4770, respectively, during the concentration-response test. Maximum repellency among other tested compounds was <40% during the concentration-response test. Blackbirds consumed 28% of rice seeds treated with 20,000 ppm GWN-4770 and 68% of untreated seeds broadcast within rice fields in southwestern Louisiana, USA. We observed 50% fewer unprotected seedlings than those treated with 10,000 ppm GWN-4770 within a drill-seeded rice field in southeastern Missouri, USA. The manufacturer subsequently applied for a United States patent for the active ingredient of GWN-4770 as an avian repellent. Although additional registration criteria and formulation optimization must be satisfied to enable the commercial availability of GWN-4770 as an avian repellent, additional efficacy studies of GWN-4770 and other promising repellents under extended field conditions are warranted for protection of newly planted and ripening rice. 相似文献
Reperfusion of the ischaemic myocardium is associated with a number of oxygen dependent processes which can damage cells. The role of oxidants in mediating reperfusion damage will be discussed. 相似文献
Abstract: Management and conservation of large carnivores increasingly includes conflicts with humans. Consequently, a greater understanding of spatiotemporal trends of conflicts is needed to efficiently allocate resources and apply targeted management. Therefore, we examined spatial and temporal distribution of American black bear (Ursus americanus; hereafter, bear)-human conflicts in Colorado, USA, related to 3 conflict types (agriculture operations, human development, and road kills). We used the Getis-Ord Gi* spatial clustering statistic to describe location and assess magnitude of bear-human conflicts in Colorado during 1986–2003 and investigated temporal trends of bear-human conflicts by type. Bear-human conflicts showed distinct spatial clustering by type, and areas of high clustering overlapped conflict types. Clustering for agriculture operations conflicts had the largest overall Gi* value and overlapped counties with high sheep production. Both human development and road-kill conflict clusters were high in areas of high-quality oak (Quercus spp.)—shrub habitat in the central and southern portions of Colorado's Front Range region and near the city of Durango in southwestern Colorado. Bear-human conflicts varied by year and type but overall increased during the 18 years. Summed across years, most conflicts were related to agriculture (32%), followed by road kills (27%) and human development (24%). The greatest proportion of agriculture operations-related conflicts (76%), human development-related conflicts (36%), and road kills (47%) occurred in 1988, 1999, and 2003, respectively. Considering that bear-human conflicts in Colorado increased over time and will likely continue to increase, we suggest wildlife managers improve data collection by obtaining detailed location data, categorizing conflict types uniformly, and applying conflict regulations consistently to strengthen inference of similar analyses. We also suggest that managers target efforts to mitigate damage by focusing on areas with high clustering of conflicts. 相似文献
Phototherapy is commonly used in the treatment of hyperbilirubinemia in newborns. No serious side effects related to phototherapy have been observed, but concerns regarding its potential to damage DNA have been expressed, based on animal or cell-culture studies. The aim of this study was to investigate, in neonates with hyperbilirubinemia, the possible relation between phototherapy and DNA damage. The study included 33 full-term newborns with non-physiological jaundice and 14 healthy newborns with physiological jaundice as controls. Phototherapy was performed with an array of six fluorescent lamps producing radiation with wavelengths of 480–520 nm at 12 μW/cm2/nm. DNA damage in lymphocytes was determined by use of the alkaline comet assay. The DNA damage increased significantly with the duration of phototherapy, as shown by measurements at 24, 48, and 72 h (P < 0.001). These findings indicate that phototherapy, widely used in neonatology units, increases DNA damage in newborns. It remains to be seen whether the genotoxic effect observed in the present study can cause any long-term health effect in phototherapy-treated infants in later life. 相似文献