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91.
Tim Helbing Caterina Carraro Alexander Francke Dr. Alice Sosic Michele De Franco Prof. Dr. Valentina Gandin Prof. Dr. Richard Göttlich Prof. Dr. Barbara Gatto 《ChemMedChem》2020,15(21):2040-2051
In this study, we describe the synthesis and biological evaluation of a set of bis-3-chloropiperidines (B−CePs) containing rigid aromatic linker structures. A modification of the synthetic strategy also enabled the synthesis of a pilot tris-3-chloropiperidine (Tri-CeP) bearing three reactive meta-chloropiperidine moieties on the aromatic scaffold. A structure–reactivity relationship analysis of B−CePs suggests that the arrangement of the reactive units affects the DNA alkylating activity, while also revealing correlations between the electron density of the aromatic system and the reactivity with biologically relevant nucleophiles, both on isolated DNA and in cancer cells. Interestingly, all aromatic 3-chloropiperidines exhibited a marked cytotoxicity and tropism for 2D and 3D cultures of pancreatic cancer cells. Therefore, the new aromatic 3-chloropiperidines appear to be promising contenders for further development of mustard-based anticancer agents aimed at pancreatic cancers. 相似文献
92.
Dr. Kristina Goncharenko Dr. Michele Mari Dr. Yves P. Auberson Brieuc Matagne 《ChemMedChem》2020,15(24):2359-2362
The European Federation for Medicinal Chemistry (EFMC) created the Young Scientists Network (YSN) to support early-career medicinal chemists and chemical biologists. By doing this, it addressed the rapid changes taking place in the scientific community and in our society, such as the rise of social media, the evolution of the gender balance in the scientific population, and educational needs. Creating the YSN was also a way to ensure that the next generation of scientists would contribute to shaping EFMC's strategy, while recognizing and addressing their needs. The YSN was set up as a very dynamic concept, and has now developed to the point where its impact is evident. The activities it promotes complement EFMC's community support and scientific opportunities, rejuvenating the Federation and preparing it for the future. It also provides opportunities for many brilliant young scientists, who do not hesitate to invest time and energy in supporting our community and shaping their own future. 相似文献
93.
94.
Italia Falcone Fabiana Conciatori Chiara Bazzichetto Emilio Bria Luisa Carbognin Paola Malaguti Gianluigi Ferretti Francesco Cognetti Michele Milella Ludovica Ciuffreda 《International journal of molecular sciences》2020,21(22)
Breast cancer was one of the first malignancies to benefit from targeted therapy, i.e., treatments directed against specific markers. Inhibitors against HER2 are a significant example and they improved the life expectancy of a large cohort of patients. Research on new biomarkers, therefore, is always current and important. AXL, a member of the TYRO-3, AXL and MER (TAM) subfamily, is, today, considered a predictive and prognostic biomarker in many tumor contexts, primarily breast cancer. Its oncogenic implications make it an ideal target for the development of new pharmacological agents; moreover, its recent role as immune-modulator makes AXL particularly attractive to researchers involved in the study of interactions between cancer and the tumor microenvironment (TME). All these peculiarities characterize AXL as compared to other members of the TAM family. In this review, we will illustrate the biological role played by AXL in breast tumor cells, highlighting its molecular and biological features, its involvement in tumor progression and its implication as a target in ongoing clinical trials. 相似文献
95.
96.
Kuwanon‐L as a New Allosteric HIV‐1 Integrase Inhibitor: Molecular Modeling and Biological Evaluation 下载免费PDF全文
Dr. Francesca Esposito Dr. Cristina Tintori Dr. Riccardo Martini Dr. Frauke Christ Prof. Zeger Debyser Roberto Ferrarese Dr. Gianluigi Cabiddu Dr. Angela Corona Dr. Elisa Rita Ceresola Dr. Andrea Calcaterra Dr. Valentina Iovine Prof. Bruno Botta Dr. Massimo Clementi Dr. Filippo Canducci Prof. Maurizio Botta Prof. Enzo Tramontano 《Chembiochem : a European journal of chemical biology》2015,16(17):2507-2512
HIV‐1 integrase (IN) active site inhibitors are the latest class of drugs approved for HIV treatment. The selection of IN strand‐transfer drug‐resistant HIV strains in patients supports the development of new agents that are active as allosteric IN inhibitors. Here, a docking‐based virtual screening has been applied to a small library of natural ligands to identify new allosteric IN inhibitors that target the sucrose binding pocket. From theoretical studies, kuwanon‐L emerged as the most promising binder and was thus selected for biological studies. Biochemical studies showed that kuwanon‐L is able to inhibit the HIV‐1 IN catalytic activity in the absence and in the presence of LEDGF/p75 protein, the IN dimerization, and the IN/LEDGF binding. Kuwanon‐L also inhibited HIV‐1 replication in cell cultures. Overall, docking and biochemical results suggest that kuwanon‐L binds to an allosteric binding pocket and can be considered an attractive lead for the development of new allosteric IN antiviral agents. 相似文献
97.
Synthesis and Antiplasmodial Activity of Novel Chloroquine Analogues with Bulky Basic Side Chains 下载免费PDF全文
Dr. Bruno Tasso Dr. Federica Novelli Dr. Michele Tonelli Dr. Anna Barteselli Dr. Nicoletta Basilico Dr. Silvia Parapini Prof. Donatella Taramelli Prof. Anna Sparatore Prof. Fabio Sparatore 《ChemMedChem》2015,10(9):1570-1583
Chloroquine is commonly used in the treatment and prevention of malaria, but Plasmodium falciparum, the main species responsible for malaria‐related deaths, has developed resistance against this drug. Twenty‐seven novel chloroquine (CQ) analogues characterized by a side chain terminated with a bulky basic head group, i.e., octahydro‐2H‐quinolizine and 1,2,3,4,5,6‐hexahydro‐1,5‐methano‐8H‐pyrido[1,2‐a][1,5]diazocin‐8‐one, were synthesized and tested for activity against D‐10 (CQ‐susceptible) and W‐2 (CQ‐resistant) strains of P. falciparum. Most compounds were found to be active against both strains with nanomolar or sub‐micromolar IC50 values. Eleven compounds were found to be 2.7‐ to 13.4‐fold more potent than CQ against the W‐2 strain; among them, four cytisine derivatives appear to be of particular interest, as they combine high potency with low cytotoxicity against two human cell lines (HMEC‐1 and HepG2) along with easier synthetic accessibility. Replacement of the 4‐NH group with a sulfur bridge maintained antiplasmodial activity at a lower level, but produced an improvement in the resistance factor. These compounds warrant further investigation as potential drugs for use in the fight against malaria. 相似文献
98.
Matthew L. Breeze Elisa Leyva‐Guerrero Grant R. Yeaman Yelena Dudin Ryan Akel Phil Brune Fred Claussen Cecil Dharmasri Jenny Golbach Rong Guo Carl Maxwell Laura Privalle Hilary Rogers Kai Liu Guomin Shan Michele Yarnall Denise Thiede Nancy Gillikin 《Journal of the American Oil Chemists' Society》2015,92(8):1085-1092
Soybean agglutinin (SBA) protein, also known as soybean lectin, is regarded as an anti‐nutrient due to its negative effect on the ability of monogastric animals to gain weight following consumption of raw soybean seed. Historically, SBA has been measured using a time‐consuming and cumbersome hemagglutination procedure. The objective of our research was to obtain a validated methodology that is precise and accurate in the measurement of SBA while allowing minimally equipped laboratories to effectively conduct the analysis, thus our focus was on evaluating an existing commercially available ELISA, an enzyme‐linked‐lectin‐assay (ELLA), and a hybrid ELISA/ELLA. A new ELLA technique that can detect and quantify lectins was chosen and modified specifically for the quantitation of SBA in soybean seed. The proposed ELLA methodology is similar to a standard sandwich ELISA, and uses polyacrylamide‐linked N‐acetylgalactosamine (Gal–NAc–PAA) for a capture phase and the biotinylated version (Gal–NAc–PAA–Biotin) for detection. Based upon the validation data, the ELLA method can precisely and accurately determine soybean lectin levels in soybean seed. The validated ELLA method was used to quantify SBA in nine commercial soybean varieties introduced between 1972 and 2008 and demonstrated that the natural variability of SBA is subject to the effects of genotype and environment. 相似文献
99.
Polycarbonate‐based composites reinforced by in situ polytetrafluoroethylene fibrillation: Preparation,thermal and rheological behavior 下载免费PDF全文
Diego Antonioli Katia Sparnacci Michele Laus Luca Boarino Maria Cristina Righetti 《应用聚合物科学杂志》2015,132(32)
Fibrillar reinforced composites of polytetrafluoroethylene (PTFE) and polycarbonate (PC) were prepared by in situ fibrillation of PTFE into PC matrix using twin screw extruder. Different samples were obtained by varying the relative ratio between PC and PTFE. The rheological properties of the PC/PTFE composites were found to depend on concentration of the PTFE fibrils. The melt strength analysis in nonisothermal conditions was also studied. The increase in force and decrease in drawability with increasing the PTFE content are associated with the PTFE fibrils formed in situ during the thermomechanical process in twin screw extruder. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42401. 相似文献
100.
Sintering behavior of Ba/Sr celsian precursor obtained from zeolite‐A by ion‐exchange method 下载免费PDF全文
Mattia Biesuz Luca Spiridigliozzi Antonello Marocco Gianfranco Dell'Agli Vincenzo M. Sglavo Michele Pansini 《Journal of the American Ceramic Society》2017,100(12):5433-5443
(Ba, Sr)‐exchanged zeolite A with composition Ba0.74Sr0.22Na0.04Al2Si2O8 was prepared by cation exchange; a mild thermal treatment converts into an amorphous phase. Successive crystallization and sintering behavior was studied by XRD, DTA, and thermodilatometric analysis. The results point out the activation of viscous flow sintering mechanisms between 900°C and 1050°C. The densification process starts when the amorphous phase reaches its glass transition temperature (897°C) and finishes when the material crystallizes forming hexacelsian. The application of an external pressure in such temperature range allows to achieve an almost complete densification, the material transforming at 1300°C into dense monoclinic celsian much below the typical processing temperature. 相似文献