Theodosis-Nobelos Panagiotis, Rekka Eleni A
Department of Pharmacy, School of Health Sciences, Frederick University, 1036 Nicosia, Cyprus.
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, 54124 Thessaloniki, Greece.
Molecules. 2025 May 27;30(11):2339. doi: 10.3390/molecules30112339.
Novel derivatives of valproic acid with biologically active moieties, such as thiomorpholine, 4-aminopyridine, serine methyl ester, trolox and the cinnamic acid derivative [()-3-(3,5-di--butyl-4-hydroxyphenyl)acrylic acid], were synthesized at satisfactory yields. The conjugation of these moieties was based on the rationale of design and evaluation of compounds with selected structural characteristics, aiming at derivatives with multiple targets. These compounds reduced acute inflammation considerably and, in most cases, more than several highly used, well-known, non-steroidal anti-inflammatory drugs. They also offered the inhibition of soybean lipoxygenase, and some of them (compounds and ) possessed radical scavenging and lipid peroxidation attenuating effects. Their antioxidant capacity was several times higher than that of the established antioxidant trolox. All the tested compounds decreased plasma lipid markers in tyloxapol-induced hyperlipidemia in rats. Compound resulted in 71.1%, 52.8% and 79.1% decrease in total cholesterol, triglycerides and LDL-cholesterol, respectively, at 150 μmol/kg (.). The effect on total and LDL cholesterol is comparable or equal to that of simvastatin, a hypocholesterolemic 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) inhibitor, however, with additionally great triglyceride-decreasing effect compared to simvastatin. Thus, the synthesized compounds may be a valuable addition to multi-functional agents acting against various degenerative disorders that implicate inflammation and lipid derangement.
合成了具有生物活性部分（如硫代吗啉、4-氨基吡啶、丝氨酸甲酯、生育三烯酚和肉桂酸衍生物[（）-3-（3,5-二叔丁基-4-羟基苯基）丙烯酸]）的新型丙戊酸衍生物，产率令人满意。这些部分的缀合基于具有选定结构特征的化合物的设计和评估原理，旨在获得具有多个靶点的衍生物。这些化合物能显著减轻急性炎症，在大多数情况下，比几种常用的、知名的非甾体抗炎药的效果还好。它们还能抑制大豆脂氧合酶，其中一些化合物（化合物 和 ）具有自由基清除和脂质过氧化减弱作用。它们的抗氧化能力比已确立的抗氧化剂生育三烯酚高几倍。所有测试化合物均能降低泰洛沙泊诱导的大鼠高脂血症中的血浆脂质标志物。化合物 在150 μmol/kg时，使总胆固醇、甘油三酯和低密度脂蛋白胆固醇分别降低了71.1%、52.8%和79.1%（.）。对总胆固醇和低密度脂蛋白胆固醇的影响与辛伐他汀相当或相同，辛伐他汀是一种降胆固醇的3-羟基-3-甲基戊二酰辅酶A还原酶（HMG-CoA）抑制剂，然而，与辛伐他汀相比，它还具有显著的降低甘油三酯的作用。因此，合成的化合物可能是对抗涉及炎症和脂质紊乱的各种退行性疾病的多功能药物的有价值补充。
