Amirinasab Maryam, Dehestani Maryam
Department of Chemistry, Shahid Bahonar University of Kerman, Kerman, Iran.
Struct Chem. 2023 Mar 29:1-9. doi: 10.1007/s11224-023-02164-6.
Despite diagnostic and therapeutic methods, cancer is a major cause of death worldwide. Since anticancer drugs affect both normal and cancer cells, targeted drug delivery systems can play a key role in reducing the destructive effects of anticancer drugs on normal cells. In this regard, the use of stimulus-sensitive polymers has increased in recent years. This study has attempted to investigate interaction of the anticancer drug cytarabine with a stimuli-sensitive polymer, human serum albumin (HSA), one of the most abundant protein in blood plasma, via computational methods at both body temperature and tumor temperature. For this purpose, molecular docking was performed using Molegro virtual Docker software to select the best ligand in terms of binding energy to simulate molecular dynamics. Then, molecular dynamics simulation was performed on human serum albumin with code (1Ao6) and cytarabine with code (AR3), using Gromacs software and the results were presented in the graphs. The simulations were performed at 310 K (normal cell temperature) and 313 K (cancer cell temperature) in 100 ns. Results showed drug release occurred at a temperature of 313 K. These findings demonstrated the sensitivity of human serum albumin to temperature.
尽管有各种诊断和治疗方法，但癌症仍是全球主要的死亡原因。由于抗癌药物对正常细胞和癌细胞都会产生影响，靶向给药系统在减少抗癌药物对正常细胞的破坏作用方面可以发挥关键作用。在这方面，近年来对刺激敏感聚合物的使用有所增加。本研究试图通过计算方法，在体温和肿瘤温度下，研究抗癌药物阿糖胞苷与一种刺激敏感聚合物——人血清白蛋白（HSA，血浆中最丰富的蛋白质之一）之间的相互作用。为此，使用Molegro虚拟对接软件进行分子对接，以根据结合能选择最佳配体来模拟分子动力学。然后，使用Gromacs软件对代码为（1Ao6）的人血清白蛋白和代码为（AR3）的阿糖胞苷进行分子动力学模拟，并将结果呈现于图表中。模拟在310K（正常细胞温度）和313K（癌细胞温度）下进行，时长为100纳秒。结果表明，在313K的温度下发生了药物释放。这些发现证明了人血清白蛋白对温度敏感。
