39245-15-3Relevant academic research and scientific papers
Synthesis and biological evaluation of novel rhodanine-based structures with antiviral activity towards HHV-6 virus
Gentili, Valentina,Turrin, Giulia,Marchetti, Paolo,Rizzo, Sabrina,Schiuma, Giovanna,Beltrami, Silvia,Cristofori, Virginia,Illuminati, Davide,Compagnin, Greta,Trapella, Claudio,Rizzo, Roberta,Bortolotti, Daria,Fantinati, Anna
, (2021/12/02)
An increased awareness of diseases associated with Human herpesvirus 6 (HHV-6) infection or reactivation has resulted in a growing interest in the evaluation of the best treatment options available for the clinical management of HHV-6 disease. However, no
Carbon–Carbon Bond Formation for the Synthesis of 5-Aryl-2-Substituted Furans Catalyzed by K3[Fe(CN)6]
Ambika,Singh, Pradeep Pratap
, (2021/10/05)
An efficient method for the carbon–carbon bond formation at C-5 position of 2-substituted furans to provide a range of π-diverse 5-aryl-2-substituted furan derivatives in 58–80% yield has been reported. The method employs several advantages such as use of catalytic amount of K3[Fe(CN)6] under mild conditions and short reaction time with high yields. Also, a variety of anilines with a variety of functional groups can be employed for the synthesis of 5-aryl-2-substituted furans. Graphic Abstract: [Figure not available: see fulltext.]
XPA INHIBITOR COMPOUNDS AND THEIR USE
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Page/Page column 46; 48; 67-68, (2019/04/16)
The present disclosure relates to certain compounds having binding affinity for XPA, and uses thereof. Specifically, the present disclosure relates to the use of XPA inhibitors as described herein in in methods of treating cancer.
Structure-based discovery of new selective small-molecule sirtuin 5 inhibitors
Liu, Sha,Ji, Sen,Yu, Zhu-Jun,Wang, Hua-Li,Cheng, Xu,Li, Wei-Jian,Jing, Li,Yu, Yamei,Chen, Qiang,Yang, Ling-Ling,Li, Guo-Bo,Wu, Yong
, p. 257 - 268 (2017/12/29)
Human sirtuin 5 (SIRT5) is a protein deacylase regulating metabolic pathways and stress responses and is implicated in metabolism-related diseases. Small-molecule inhibitors for SIRT5 are sought as chemical tools and potential therapeutics. Herein, we proposed a customized virtual screening approach targeting catalytically important and unique residues Tyr102 and Arg105 of SIRT5. Of the 20 tested virtual screening hits, six compounds displayed marked inhibitory activities against SIRT5. For the hit compound 19, a series of newly synthesized (E)-2-cyano-N-phenyl-3-(5-phenylfuran-2-yl)acrylamide derivatives/analogues were carried out structure–activity relationship analyses, resulting in new more potent inhibitors, among which 37 displayed the most potent inhibition to SIRT5 with an IC50 value of 5.59?±?0.75?μM. The biochemical studies revealed that 37 likely acts via competitive inhibition with the succinyl-lysine substrate, rather than the NAD+ cofactor, and it manifested substantial selectivity for SIRT5 over SIRT2 and SIRT6. This study will aid further efforts to develop new selective SIRT5 inhibitors as tools and therapeutics.
Design and Structure-Guided Development of Novel Inhibitors of the Xeroderma Pigmentosum Group A (XPA) Protein-DNA Interaction
Gavande, Navnath S.,Vandervere-Carozza, Pamela,Mishra, Akaash K.,Vernon, Tyler L.,Pawelczak, Katherine S.,Turchi, John J.
, p. 8055 - 8070 (2017/10/18)
XPA is a unique and essential protein required for the nucleotide excision DNA repair pathway and represents a therapeutic target in oncology. Herein, we are the first to develop novel inhibitors of the XPA-DNA interaction through structure-guided drug design efforts. Ester derivatives of the compounds 1 (X80), 22, and 24 displayed excellent inhibitory activity (IC50 of 0.82 ± 0.18 μM and 1.3 ± 0.22 μM, respectively) but poor solubility. We have synthesized novel amide derivatives that retain potency and have much improved solubility. Furthermore, compound 1 analogs exhibited good specificity for XPA over RPA (replication protein A), another DNA-binding protein that participates in the nucleotide excision repair (NER) pathway. Importantly, there were no significant interactions observed by the X80 class of compounds directly with DNA. Molecular docking studies revealed a mechanistic model for the interaction, and these studies could serve as the basis for continued analysis of structure-activity relationships and drug development efforts of this novel target.
KU INHIBITORS AND THEIR USE
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Page/Page column 55; 56, (2017/12/29)
The present disclosure relates to certain compounds having binding affinity for Ku, and uses thereof. Specifically, the present disclosure relates to the use of Ku inhibitors as described herein in site-specific genome engineering technologies, including but not limited to CRISPR/Cas9, Zinc finger nuclease (ZFN), Transcription activator-like effector nuclease (TALEN), and meganuclease. The present disclosure also relates to kits useful for site-specific genome engineering that include at least one compound as described herein.
D-3-phosophoglycerate dehydrogenase allosteric inhibitor and application thereof
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Paragraph 0046-0049, (2018/02/04)
The invention discloses a D-3-phosophoglycerate dehydrogenase allosteric inhibitor and an application thereof. The structure of the D-3-phosophoglycerate dehydrogenase allosteric inhibitor is shown in a formula I defined in the specification, wherein R1,
Identification of N-acylhydrazone derivatives as novel lactate dehydrogenase A inhibitors
Rupiani, Sebastiano,Buonfiglio, Rosa,Manerba, Marcella,Di Ianni, Lorenza,Vettraino, Marina,Giacomini, Elisa,Masetti, Matteo,Falchi, Federico,Di Stefano, Giuseppina,Roberti, Marinella,Recanatini, Maurizio
supporting information, p. 63 - 70 (2015/06/30)
Abstract Glycolysis is drastically increased in tumors and it is the main route to energy production with a minor use of oxidative phosphorylation. Among the key enzymes in the glycolytic process, LDH is emerging as one of the most interesting targets for the development of new inhibitors. In this context, in the present work, we carried out a virtual screening procedure followed by chemical modifications of the identified structures according to a "hit-to-lead" process. The effects of the new molecules were preliminary probed against purified human LDH-A. The compounds active at low micromolar level were additionally characterized for their activity on some cellular metabolic processes by using Raji human cell line. Within the series, 1 was considered the best candidate, and a more detailed characterization of its biological properties was performed. In Raji cells exposed to compound 1 we evidenced the occurrence of effects usually observed in cancer cells after LDH-A inhibition: reduced lactate production and NAD/NADH ratio, apoptosis. The flow cytometry analysis of treated cells also showed cell cycle changes compatible with effects exerted at the glycolytic level. Finally, in agreement with the data obtained with other inhibitors or by silencing LDH-A expression, compound 1 was found to increase Raji cells response to some commonly used chemotherapeutic agents. Taken together, all these finding are in support of the LDH-A inhibiting activity of compound 1.
Synthesis of novel arylfurfurylchalcones
Aslam, Samina,Asif, Nadia,Khan, Muhammad Naeem,Khan, Misbahul Ain,Munawar, Munawar Ali,Nasrullah, Muhammad
, p. 7738 - 7742 (2013/09/23)
Various aryl furans-2-carbaldehyde chalcones with different acetophenones were prepared and characterized through their elemental analyses and spectroscopic techniques (FTIR, 1H NMR, 13C NMR and mass spectra).
Synthesis of novel diarylpyrrole-2-carbaldehydes by ring transformations
Aslam, Samina,Nazeer, Areesha,Khan, Muhammad Naeem,Parveen, Najma,Khan, Misbahul Ain,Munawar, Munawar Ali
, p. 9595 - 9600 (2014/01/06)
Various diarylpyrrole-2-carbaldehydes were prepared by ring transformation of arylfuran-2-carbaldehydes with anilines in the presence of an acid. The synthesized compounds were characterized through elemental analysis and spectroscopic techniques (FTIR, 1H NMR, 13C NMR and mass spectra).
