PDF(Pubmed)
Abstract：
Development of drugs that are selectively toxic to cancer cells and safe to normal cells is crucial in cancer treatment. Evaluation of membrane permeability is a key metric for successful drug development. In this study, we have used in silico molecular models of lipid bilayers to explore the effect of phosphatidylserine (PS) exposure in cancer cells on membrane permeation of natural compounds Withaferin A (Wi-A), Withanone (Wi-N), Caffeic Acid Phenethyl Ester (CAPE) and Artepillin C (ARC). Molecular dynamics simulations were performed to compute permeability coefficients. The results indicated that the exposure of PS in cancer cell membranes facilitated the permeation of Wi-A, Wi-N and CAPE through a cancer cell membrane when compared to a normal cell membrane. In the case of ARC, PS exposure did not have a notable influence on its permeability coefficient. The presented data demonstrated the potential of PS exposure-based models for studying cancer cell selectivity of drugs.
摘要：
开发对癌细胞有选择性毒性并对正常细胞安全的药物在癌症治疗中至关重要。膜渗透性的评估是成功药物开发的关键指标。在这项研究中,我们使用脂质双层的计算机分子模型来探索癌细胞中磷脂酰丝氨酸（PS）暴露对天然化合物WithaferinA（Wi-A）膜渗透的影响，Withanone(Wi-N),咖啡酸苯乙酯（CAPE）和ArtepillinC（ARC）。进行分子动力学模拟以计算渗透系数。结果表明，PS在癌细胞膜中的暴露促进了Wi-A的渗透，当与正常细胞膜相比时,Wi-N和CAPE穿过癌细胞膜。在ARC的情况下，PS暴露对其渗透系数没有显着影响。所提供的数据证明了基于PS暴露的模型用于研究药物的癌细胞选择性的潜力。
