Počet záznamů: 1
Synthesis and Evaluation of the Biological Profile of Novel Analogues of Nucleosides and of Potential Mimetics of Sugar Phosphates and Nucleotides
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SYSNO ASEP 0453470 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Synthesis and Evaluation of the Biological Profile of Novel Analogues of Nucleosides and of Potential Mimetics of Sugar Phosphates and Nucleotides Tvůrce(i) Xavier, N.M. (PT)
Lucas, S.D. (PT)
Jorda, Radek (UEB-Q) ORCID, RID
Schwarz, S. (DE)
Loesche, A. (DE)
Csuk, R. (DE)
Oliveira, M.C. (PT)Zdroj.dok. Synlett. - : Georg Thieme Verlag - ISSN 0936-5214
Roč. 26, č. 19 (2015), s. 2663-2672Poč.str. 10 s. Jazyk dok. eng - angličtina Země vyd. DE - Německo Klíč. slova nucleosides ; nucleotides ; carbohydrates Vědní obor RIV EB - Genetika a molekulární biologie CEP LO1204 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora UEB-Q - RVO:61389030 UT WOS 000365298100008 DOI 10.1055/s-0035-1560591 Anotace The synthesis of purine/triazole 6'-isonucleosides and of glucuronic acid/glucuronamide-derived N-glycosylsulfonohydrazides through efficient and stereo- or regioselective methodologies is described. Their structures were envisaged to mimic nucleosides, sugar phosphates, or nucleotides, and were expected to provide potential inhibitors of therapeutically relevant enzymes, the active sites of which could potentially bind their structural fragments or functional groups. Such enzymes include cholinesterases, carbonic anhydrase II (CA-II) and cyclin-dependent kinase 2 (CDK-2). A (triazolyl)methyl amide-linked disaccharide nucleoside, based on a new prospective structural framework for analogues of nucleoside diphosphate sugars, was synthesized. The synthetic strategies employed unprotected or partially protected carbohydrate derivatives as precursors, including ribose, glucuronic acid, glucuronolactone, and glycopyranosides and relied on stereoselective N-glycosylation, regioselective Mitsunobu coupling and click chemistry' approaches. Some 6'-isonucleosides and triazole-containing glycoderivatives displayed moderate selective acetylcholinesterase inhibitory activities. The best inhibitor was an aminomethyltriazole 6'-isonucleoside with a K-i value of 11.9M. N-Glucuronylsulfonohydrazide showed good inhibition of CA-II (K-i=9.5M). Molecular docking of the most active compounds into the effected enzymes showed interactions with key amino acid residues for substrate recognition. In addition, the tested compounds did not show toxicity to normal cells. Pracoviště Ústav experimentální botaniky Kontakt David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469 Rok sběru 2016
Počet záznamů: 1