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Synthesis and antiglycation activity of 3-phenacyl substituted thiazolium salts, new analogs of Alagebrium
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2023-11-06 , DOI: 10.1111/cbdd.14391 Alexander Ozerov 1 , Darya Merezhkina 1 , Fedor I. Zubkov 2 , Roman Litvinov 3 , Umida Ibragimova 3 , Nikita Valuisky 3 , Alexander Borisov 3 , Alexander Spasov 3
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2023-11-06 , DOI: 10.1111/cbdd.14391 Alexander Ozerov 1 , Darya Merezhkina 1 , Fedor I. Zubkov 2 , Roman Litvinov 3 , Umida Ibragimova 3 , Nikita Valuisky 3 , Alexander Borisov 3 , Alexander Spasov 3
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After preliminary ab initio calculations, 3-phenacyl substituted thiazolium salts, analogs of Alagebrium, were synthesized and investigated in vitro as glycation reaction inhibitors. The most part of investigations focused on the potential of the title compounds to attenuate the formation of fluorescent AGEs as well on their ability to disrupt the cross-linking formation among glycated proteins. Additionally, the capability of thiazolium salts to deglycate in the reaction of early glycation products with nitroblue tetrazolium was determined. Cytotoxicological properties of the title compounds were evaluated using LDH and MTT assays. The leader compound (3-[2-(biphenyl-4-yl)-2-oxoethyl]-1,3-thiazol-3-ium bromide) in a 50 mg/kg dose (p.o. 14 days) was further tested within an in vivo carbonyl stress model (rats, methylglyoxal 86.25 mg/kg/d, i.p., 14 days). As a result, the leader-molecule revealed a high effectiveness against all three examined mechanisms of glycation reaction inhibition in in vitro tests and was able to suppress capacity of methylglyoxal to form AGEs in vivo.
中文翻译：
Alagebrium 的新类似物 3-苯甲酰基取代的噻唑鎓盐的合成和抗糖化活性
经过初步的从头计算，合成了 3-苯甲酰基取代的噻唑鎓盐（Alagebrium 的类似物），并作为糖化反应抑制剂进行了体外研究。大部分研究集中在标题化合物减弱荧光 AGE 形成的潜力以及它们破坏糖化蛋白之间交联形成的能力。此外，还测定了噻唑鎓盐在早期糖基化产物与硝基蓝四唑的反应中去糖化的能力。使用 LDH 和 MTT 测定评估标题化合物的细胞毒理学性质。 50 mg/kg 剂量（口服 14 天）的先导化合物（3-[2-（联苯-4-基）-2-氧代乙基]-1,3-噻唑-3-溴化鎓）在体内羰基应激模型（大鼠，甲基乙二醛 86.25 mg/kg/d，腹腔注射，14 天）。结果，前导分子在体外测试中显示出对所有三种糖化反应抑制机制的高效作用，并且能够抑制甲基乙二醛在体内形成 AGE 的能力。
更新日期：2023-11-06
中文翻译：
Alagebrium 的新类似物 3-苯甲酰基取代的噻唑鎓盐的合成和抗糖化活性
经过初步的从头计算，合成了 3-苯甲酰基取代的噻唑鎓盐（Alagebrium 的类似物），并作为糖化反应抑制剂进行了体外研究。大部分研究集中在标题化合物减弱荧光 AGE 形成的潜力以及它们破坏糖化蛋白之间交联形成的能力。此外，还测定了噻唑鎓盐在早期糖基化产物与硝基蓝四唑的反应中去糖化的能力。使用 LDH 和 MTT 测定评估标题化合物的细胞毒理学性质。 50 mg/kg 剂量（口服 14 天）的先导化合物（3-[2-（联苯-4-基）-2-氧代乙基]-1,3-噻唑-3-溴化鎓）在体内羰基应激模型（大鼠，甲基乙二醛 86.25 mg/kg/d，腹腔注射，14 天）。结果，前导分子在体外测试中显示出对所有三种糖化反应抑制机制的高效作用，并且能够抑制甲基乙二醛在体内形成 AGE 的能力。
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