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961.
The greenhouse whitefly, Trialeurodes vaporariorum Westwood, is an important pest of field and greenhouse crops of horticultural and ornamental plants. In integrated pest management programs its control is mainly based on the release of biological control agents and application of chemical insecticides. Neonicotinoids are relatively new chemicals currently applied for the chemical control of T. vaporariorum. However, cases of development of insecticide resistance to neonicotinoids have already been reported. The state of resistance to neonicotinoid insecticides for populations of the greenhouse whitefly in Greece is currently unknown. The objective of our study was to screen a number of whitefly populations for resistance to the neonicotinoids imidacloprid and thiacloprid. Seven whitefly populations were collected from tomato greenhouse crops from different areas of central and northern Greece. LC50 values were estimated for all populations following the method proposed by the Insecticide Resistance Action Committee (IRAC). The development of resistance to both neonicotinoids was confirmed for all tested populations with resistance ratios ranging from 1.5 to 4.4-fold and from 1.4 to 12.2-fold for imidacloprid and thiacloprid, respectively. We discuss our results with regard to the development of neonicotinoid resistance in T. vaporariorum populations and its implications for whitefly control. 相似文献
962.
Yonatan B. Tzur Ari E. Friedland Saravanapriah Nadarajan George M. Church John A. Calarco Monica P. Colaiácovo 《Genetics》2013,195(3):1181-1185
We adapted the CRISPR–Cas9 system for template-mediated repair of targeted double-strand breaks via homologous recombination in Caenorhabditis elegans, enabling customized and efficient genome editing. This system can be used to create specific insertions, deletions, and base pair changes in the germline of C. elegans. 相似文献
963.
Magali Moreau Timothy Westlake Giulio Zampogna George Popescu Miaoying Tian Christos Noutsos Sorina Popescu 《The Plant journal : for cell and molecular biology》2013,76(4):603-614
Salicylic acid (SA) is a small phenolic molecule with hormonal properties, and is an essential component of the immune response. SA exerts its functions by interacting with protein targets; however, the specific cellular components modulated by SA and critical for immune signal transduction are largely unknown. To uncover cellular activities targeted by SA, we probed Arabidopsis protein microarrays with a functional analog of SA. We demonstrate that thimet oligopeptidases (TOPs) constitute a class of SA‐binding enzymes. Biochemical evidence demonstrated that SA interacts with TOPs and inhibits their peptidase activities to various degrees both in vitro and in plant extracts. Functional characterization of mutants with altered TOP expression indicated that TOP1 and TOP2 mediate SA‐dependent signaling and are necessary for the immune response to avirulent pathogens. Our results support a model whereby TOP1 and TOP2 act in separate pathways to modulate SA‐mediated cellular processes. 相似文献
964.
Shyh-Ming Yang Yuting Tang Rui Zhang Huajun Lu Gee-Hong Kuo Michael D. Gaul Yaxin Li George Ho James G. Conway Yin Liang James M. Lenhard Keith T. Demarest William V. Murray 《Bioorganic & medicinal chemistry letters》2013,23(24):6773-6776
A new series of urea-based, 4-bicyclic heteroaryl-piperidine derivatives as potent SCD1 inhibitors is described. The structure–activity relationships focused on bicyclic heteroarenes and aminothiazole–urea portions are discussed. A trend of dose-dependent decrease in body weight gain in diet-induced obese (DIO) mice is also demonstrated. 相似文献
965.
Zhongli Gao William J. Hurst Etienne Guillot Raisa Nagorny Marie-Pierre Pruniaux James A. Hendrix Pascal G. George 《Bioorganic & medicinal chemistry letters》2013,23(14):4044-4047
This Letter describes the asymmetric synthesis of the four stereoisomers (8a–8d) of a potent and highly selective histamine H3 receptor (H3R) antagonist, 5-fluoro-2-methyl-N-[2-methyl-4-(2-methyl[1,3′]bipyrrolidinyl-1′-yl) phenyl]benzamide (1). The physico-chemical properties, in vitro H3R affinities and ADME of 8a–8d were determined. Stereoisomer 8c (2S,3′S) displayed superior in vitro H3R affinity over other three stereoisomers and was selected for further profiling in in vivo PK and drug safety. Compound 8c exhibited excellent PK properties with high exposure, desired brain to plasma ratio and reasonable brain half life. However, all stereoisomers showed similar unwanted hERG affinities. 相似文献
966.
Stacy Van Epps Bryan Fiamengo Jeremy Edmunds Anna Ericsson Kristine Frank Michael Friedman Dawn George Jonathan George Eric Goedken Brian Kotecki Gloria Martinez Philip Merta Michael Morytko Shashank Shekhar Barbara Skinner Kent Stewart Jeffrey Voss Grier Wallace Neil Wishart 《Bioorganic & medicinal chemistry letters》2013,23(3):693-698
Interest in therapeutic kinase inhibitors continues to grow beyond success in oncology. To date, ATP-mimetic kinase inhibitors have focused primarily on monocyclic and bicyclic heterocyclic cores. We sought to expand on the repertoire of potential cores for kinase inhibition by exploring tricyclic variants of classical bicyclic hinge binding motifs such as pyrrolopyridine and pyrrolopyrazine. Herein we describe the syntheses of eight alternative tricyclic cores as well as in vitro screening results for representative kinases of potential therapeutic interest. 相似文献
967.
Zhongli Gao William J. Hurst Etienne Guillot Werngard Czechtizky Ulrike Lukasczyk Raisa Nagorny Marie-Pierre Pruniaux Lothar Schwink Juan Antonio Sanchez Siegfried Stengelin Lei Tang Irvin Winkler James A. Hendrix Pascal G. George 《Bioorganic & medicinal chemistry letters》2013,23(11):3416-3420
A series of structurally novel aryl ureas was derived from optimization of the HTS lead as selective histamine H3 receptor (H3R) antagonists. The SAR was explored and the data obtained set up the starting point and foundation for further optimization. The most potent tool compounds, as exemplified by compounds 2l, 5b, 5d, and 5e, displayed antagonism potencies in the subnanomolar range in in vitro human-H3R FLIPR assays and rhesus monkey H3R binding assays. 相似文献
968.
Timothy A. Stammers René Coulombe Martin Duplessis Gulrez Fazal Alexandre Gagnon Michel Garneau Sylvie Goulet Araz Jakalian Steven LaPlante Jean Rancourt Bounkham Thavonekham Dominik Wernic George Kukolj Pierre L. Beaulieu 《Bioorganic & medicinal chemistry letters》2013,23(24):6879-6885
Optimization efforts on the anthranilic acid-based Thumb Pocket 2 HCV NS5B polymerase inhibitors 1 and 2 resulted in the identification of multiple structural elements that contributed to improved cell culture potency. The additive effect of these elements resulted in compound 46, an inhibitor with enzymatic (IC50) and cell culture (EC50) potencies of less than 100 nanomolar. 相似文献
969.
Xiaojun Han Rita L. Civiello Charles M. Conway Deborah A. Cook Carl D. Davis Andrew P. Degnan Xiang-Jun Jiang Robert Macci Neil R. Mathias Paul Moench Sokhom S. Pin Richard Schartman Laura J. Signor George Thalody George Tora Valerie Whiterock Cen Xu John E. Macor Gene M. Dubowchik 《Bioorganic & medicinal chemistry letters》2013,23(12):3674
970.
Swati P. Mercer Anthony J. Roecker Susan Garson Duane R. Reiss C. Meacham Harrell Kathy L. Murphy Joseph G. Bruno Rodney A. Bednar Wei Lemaire Donghui Cui Tamara D. Cabalu Cuyue Tang Thomayant Prueksaritanont George D. Hartman Steven D. Young Christopher J. Winrow John J. Renger Paul J. Coleman 《Bioorganic & medicinal chemistry letters》2013,23(24):6620-6624
The orexin (or hypocretin) system has been identified as a novel target for the treatment of insomnia due to the wealth of biological and genetic data discovered over the past decade. Recently, clinical proof-of-concept was achieved for the treatment of primary insomnia using dual (OX1R/OX2R) orexin receptor antagonists. However, elucidation of the pharmacology associated with selective orexin-2 receptor antagonists (2-SORAs) has been hampered by the lack of orally bioavailable, highly selective small molecule probes. Herein, the discovery and optimization of a novel series of 2,5-diarylnicotinamides as potent and orally bioavailable orexin-2 receptor selective antagonists is described. A compound from this series demonstrated potent sleep promotion when dosed orally to EEG telemetrized rats. 相似文献