Parmenopoulou Vanessa, Manta Stella, Dimopoulou Athina, Kollatos Nikolaos, Schols Dominique, Komiotis Dimitri
1Laboratory of Bioorganic Chemistry, Department of Biochemistry and Biotechnology, University of Thessaly, 26 Ploutonos Str., 41 221 Larissa, Greece.
2Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, Louvain, Belgium.
Med Chem Res. 2016;25(5):932-940. doi: 10.1007/s00044-016-1539-5. Epub 2016 Feb 29.
Novel classes of acetylated and fully deprotected -acyl--d-glucopyranosylamines and ureas have been synthesized and biologically evaluated. Acylation of the per--acetylated -d-glucopyranosylurea (), easily prepared via its corresponding phosphinimine derivative, by zinc chloride catalyzed reaction of the corresponding acyl chlorides RCOCl (-) gave the protected -acyl--d-glucopyranosylureas (-), in acceptable-to-moderate yields. Subsequent deacetylation of analogues - under Zemplén conditions afforded the fully deprotected derivatives , while the desired urea was formed after treatment of with dibutyltin oxide. All protected and unprotected compounds were examined for their cytotoxic activity in different L1210, CEM and HeLa tumor cell lines and were also evaluated against a broad panel of DΝΑ and RNA viruses. Derivative exhibited cytostatic activity against the three evaluated tumor cell lines (IC 9-24 μΜ) and might be the basis for the synthesis of structure-related derivatives with improved cytostatic potential. Only analogue weakly but significantly inhibited the replication of parainfluenza-3 virus, Sindbis virus and Coxsackie virus B4 in cell cultures at concentrations of 45-58 μM.
已合成新型乙酰化和完全脱保护的 - 酰基 -β -D - 吡喃葡萄糖胺和脲类化合物，并进行了生物学评估。通过相应的磷亚胺衍生物容易制备的全 -O - 乙酰化 -β -D - 吡喃葡萄糖基脲（），经相应的酰氯RCOCl（ - ）在氯化锌催化下反应进行酰化，得到受保护的 - 酰基 -β -D - 吡喃葡萄糖基脲（ - ），产率可接受至中等。在Zemplén条件下对类似物 - 进行后续脱乙酰化得到完全脱保护的衍生物 ，而在用二丁基氧化锡处理 后形成所需的脲 。所有受保护和未受保护的化合物均在不同的L1210、CEM和HeLa肿瘤细胞系中检测其细胞毒性活性，并针对多种DNA和RNA病毒进行了评估。衍生物 对三种评估的肿瘤细胞系表现出细胞生长抑制活性（IC 9 - 24 μΜ），可能是合成具有改善细胞生长抑制潜力的结构相关衍生物的基础。仅类似物 在浓度为45 - 58 μM时对细胞培养物中的副流感病毒3型、辛德毕斯病毒和柯萨奇病毒B4的复制有微弱但显著的抑制作用。
