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10.1016/j.ejmech.2019.111956 http://scihub22266oqcxt.onion/10.1016/j.ejmech.2019.111956 31841728!7115507!31841728     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Eur+J+Med+Chem 2020 ; 187 (ä): 111956 Nephropedia Template TP {{tp|p=31841728|t=2020. Identification of 6 -beta-fluoro-homoaristeromycin as a potent inhibitor of chikungunya virus replication |pdf=|usr=}}{{31841728}} gab.com Text Identification of 6 -beta-fluoro-homoaristeromycin as a potent inhibitor of chikungunya virus replication JO: Eur J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=31841728 #FOAvip We have reported on aristeromycin (1) and 6'-fluorinated-aristeromycin analogues (2), which are active against RNA viruses such as Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), Zika virus (ZIKV), and Chikungunya virus (CHIKV). However, these exhibit substantial cytotoxicity. As this cytotoxicity may be attributed to 5'-phosphorylation, we designed and synthesized one-carbon homologated 6'-fluorinated-aristeromycin analogues. This modification prevents 5'-phosphorlyation by cellular kinases, whereas the inhibitory activity towards S-adenosyl-l-homocysteine (SAH) hydrolase will be retained. The enantiomerically pure 6'-fluorinated-5'-homoaristeromycin analogues 3a-e were synthesized via the electrophilic fluorination of the silyl enol ether with Selectfluor, using a base-build up approach as the key steps. All synthesized compounds exhibited potent inhibitory activity towards SAH hydrolase, among which 6'-beta-fluoroadenosine analogue 3a was the most potent (IC(50) = 0.36 muM). Among the compounds tested, 6'-beta-fluoro-homoaristeromycin 3a showed potent antiviral activity (EC(50) = 0.12 muM) against the CHIKV, without noticeable cytotoxicity up to 250 muM. Only 3a displayed anti-CHIKV activity, whereas both3a and 3b inhibited SAH hydrolase with similar IC(50) values (0.36 and 0.37 muM, respectively), which suggested that 3a's antiviral activity did not merely depend on the inhibition of SAH hydrolase. This is further supported by the fact that the antiviral effect was specific for CHIKV and some other alphaviruses and none of the homologated analogues inhibited other RNA viruses, such as SARS-CoV, MERS-CoV, and ZIKV. The potent inhibition and high selectivity index make 6'-beta-fluoro-homoaristeromycin (3a) a promising new template for the development of antivirals against CHIKV, a serious re-emerging pathogen that has infected millions of people over the past 15 years. Twit Text FOAVip Identification of 6 -beta-fluoro-homoaristeromycin as a potent inhibitor of chikungunya virus replication ????Eur J Med Chem http://www.kidney.de/pget.php?&tw=1&pmid=31841728 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=31841728 #FOAvip English Wikipedia <ref>{{Cite pmid|31841728}}</ref> Identification of 6 -beta-fluoro-homoaristeromycin as a potent inhibitor of chikungunya virus replication #MMPMID31841728 Shin YS; Jarhad DB; Jang MH; Kovacikova K; Kim G; Yoon JS; Kim HR; Hyun YE; Tipnis AS; Chang TS; van Hemert MJ; Jeong LS Eur J Med Chem 2020[Feb]; 187 (ä): 111956 PMID31841728show ga We have reported on aristeromycin (1) and 6'-fluorinated-aristeromycin analogues (2), which are active against RNA viruses such as Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), Zika virus (ZIKV), and Chikungunya virus (CHIKV). However, these exhibit substantial cytotoxicity. As this cytotoxicity may be attributed to 5'-phosphorylation, we designed and synthesized one-carbon homologated 6'-fluorinated-aristeromycin analogues. This modification prevents 5'-phosphorlyation by cellular kinases, whereas the inhibitory activity towards S-adenosyl-l-homocysteine (SAH) hydrolase will be retained. The enantiomerically pure 6'-fluorinated-5'-homoaristeromycin analogues 3a-e were synthesized via the electrophilic fluorination of the silyl enol ether with Selectfluor, using a base-build up approach as the key steps. All synthesized compounds exhibited potent inhibitory activity towards SAH hydrolase, among which 6'-beta-fluoroadenosine analogue 3a was the most potent (IC(50) = 0.36 muM). Among the compounds tested, 6'-beta-fluoro-homoaristeromycin 3a showed potent antiviral activity (EC(50) = 0.12 muM) against the CHIKV, without noticeable cytotoxicity up to 250 muM. Only 3a displayed anti-CHIKV activity, whereas both3a and 3b inhibited SAH hydrolase with similar IC(50) values (0.36 and 0.37 muM, respectively), which suggested that 3a's antiviral activity did not merely depend on the inhibition of SAH hydrolase. This is further supported by the fact that the antiviral effect was specific for CHIKV and some other alphaviruses and none of the homologated analogues inhibited other RNA viruses, such as SARS-CoV, MERS-CoV, and ZIKV. The potent inhibition and high selectivity index make 6'-beta-fluoro-homoaristeromycin (3a) a promising new template for the development of antivirals against CHIKV, a serious re-emerging pathogen that has infected millions of people over the past 15 years. |Adenosine/*analogs & derivatives/chemical synthesis/chemistry/pharmacology[MESH] |Antiviral Agents/chemical synthesis/chemistry/*pharmacology[MESH] |Chikungunya virus/*drug effects[MESH] |Crystallography, X-Ray[MESH] |Dose-Response Relationship, Drug[MESH] |Microbial Sensitivity Tests[MESH] |Models, Molecular[MESH] |Molecular Structure[MESH] |Structure-Activity Relationship[MESH]Identification of 6 -beta-fluoro-homoaristeromycin as a potent inhibit(epmc).pdf DeepDyve Pubget Overpricing