Rosa Antonella, Pollastro Federica, Sogos Valeria, Piras Franca
Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy.
Department of Pharmaceutical Sciences, University of Eastern Piedmont "Amedeo Avogadro", 28100 Novara, Italy.
Molecules. 2025 Apr 13;30(8):1742. doi: 10.3390/molecules30081742.
The cytotoxic and apoptotic properties of four bioactive natural compounds, the prenylated α-pyronephloroglucinol heterodimer arzanol (ARZ), the methoxylated flavones eupatilin (EUP) and xanthomicrol (XAN), and the sesquiterpene zerumbone (ZER), were compared in SH-SY5Y human neuroblastoma cells to assess their potential as neuroblastoma-specific therapeutics. EUP, XAN, and ZER (2.5-100 μM) exerted marked significant cytotoxicity (MTT assay) and morphological changes after 24 h of incubation, following the order XAN > ZER > EUP > ARZ (no toxic effect). The propidium iodide fluorescence assay (PI, red fluorescence) and NucView 488 assay (NV, green fluorescence) evidenced a significant increase in the apoptotic cell number, vs. controls, in SH-SY5Y cells pre-incubated for 2 h with the compounds, in the following order of apoptotic potency: XAN > EUP > ZER > ARZ. The PubChem database and freely accessible web tools SwissADME, pkCSM-pharmacokinetics, and SwissTargetPrediction were used to assess the physicochemical/pharmacokinetic properties and potential protein targets of the compounds. At 50 μM, a positive correlation (r = 0.917) between values of % viability reduction and % human intestinal absorption (bioavailability) was observed, indicating a marked contribution of compound membrane permeability to cytotoxicity in SH-SY5Y cells. The capacity of compounds to induce apoptosis emerged as inversely correlated to the computed lipophilicity (r = -0.885).
比较了四种生物活性天然化合物的细胞毒性和凋亡特性，这四种化合物分别是异戊烯基化的α-吡喃酮间苯三酚异二聚体arzanol（ARZ）、甲氧基黄酮灯盏花乙素（EUP）和黄腐醇（XAN）以及倍半萜姜酮（ZER），在SH-SY5Y人神经母细胞瘤细胞中评估它们作为神经母细胞瘤特异性治疗药物的潜力。EUP、XAN和ZER（2.5 - 100 μM）在孵育24小时后表现出显著的细胞毒性（MTT法）和形态学变化，顺序为XAN > ZER > EUP > ARZ（无毒性作用）。碘化丙啶荧光测定法（PI，红色荧光）和NucView 488测定法（NV，绿色荧光）证明，与对照组相比，在与化合物预孵育2小时的SH-SY5Y细胞中，凋亡细胞数量显著增加，凋亡效力顺序为：XAN > EUP > ZER > ARZ。使用PubChem数据库以及可免费访问的网络工具SwissADME、pkCSM-药代动力学和SwissTargetPrediction来评估这些化合物的物理化学/药代动力学特性和潜在的蛋白质靶点。在50 μM时，观察到活力降低百分比值与人体肠道吸收百分比（生物利用度）之间呈正相关（r = 0.917），表明化合物膜通透性对SH-SY5Y细胞中的细胞毒性有显著贡献。化合物诱导凋亡的能力与计算得出的亲脂性呈负相关（r = -0.885）。
