揭示吗啉鎓表面活性离子液体对表皮生长因子受体抑制作用的潜力:合成、结合分子对接、动力学及体外研究

Unveiling the Potential of Morpholinium Surface Active Ionic Liquids for Epidermal Growth Factor Receptor Inhibition: Synthesis, Integrating Molecular Docking, Dynamics, and In Vitro Studies.

作者信息

Viradiya Ravi, Patel Mehul, Rohit Shishir, Shah Umang, Patel Gayatri, Vashi Ankur, Shah Pranay, Panjabi Sanjay

机构信息

Department of Chemical Sciences, P. D. Patel Institute of Applied Sciences, Charotar University of Science and Technology, CHARUSAT - Campus, Changa 388421, India.

Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT - Campus, Changa 388421, India.

出版信息

ACS Omega. 2025 May 16;10(20):20562-20569. doi: 10.1021/acsomega.5c01250. eCollection 2025 May 27.

Abstract

AIM

To explore the potential for epidermal growth factor receptor (EGFR) inhibition by synthesizing two morpholinium-containing surface active ionic liquids (SAILs) with long alkyl side chains: -dodecyl--methylmorpholinium salicylate ([Cmmor] [Sal]) and -dodecyl--methylmorpholinium 3-hydroxy-2-naphthoate ([Cmmor]-[3--2-]).

METHODS

Synthesis of SAILs by quaternization and neutralization metathesis reactions, molecular docking, simulation, and in vitro studies were integrated. Specifically, this finding draws attention to the pressing global issue of cancer-related mortality and underscores the pivotal role of inhibiting the EGFR in addressing nonsmall cell lung cancer, which is a leading cause of cancer deaths worldwide.

RESULTS

The data indicating lower inhibitory concentration values for A549 cells than for healthy cells underscore the promising potential of SAILs as potential active agents in cancer therapy. Their ability to exhibit cytotoxic effects specifically on cancer cells while sparing healthy cells has significant implications for targeted cancer treatment strategies. This selectivity not only minimizes the risk of adverse effects on healthy tissues but also enhances the therapeutic efficacy of ILs in combating cancer progression.

CONCLUSION

These findings pave the way for further exploration of SAILs as potential candidates for therapeutic applications, particularly in lung cancer therapy using animal models of malignancies. However, clinical applications in terms of regulatory approval, biocompatibility, and synergistic action with drugs to ensure patient safety are necessary.

摘要

目的

通过合成两种具有长烷基侧链的含吗啉鎓表面活性离子液体(SAILs):十二烷基甲基吗啉鎓水杨酸盐([Cmmor][Sal])和十二烷基甲基吗啉鎓3-羟基-2-萘酸盐([Cmmor][3-H-2-N]),探索表皮生长因子受体(EGFR)抑制的潜力。

方法

将SAILs的季铵化和中和复分解反应合成、分子对接、模拟及体外研究结合起来。具体而言,这一发现凸显了癌症相关死亡率这一紧迫的全球问题,并强调了抑制EGFR在解决非小细胞肺癌方面的关键作用,非小细胞肺癌是全球癌症死亡的主要原因。

结果

数据表明A549细胞的抑制浓度值低于健康细胞,这突出了SAILs作为癌症治疗潜在活性剂的前景。它们对癌细胞具有特异性细胞毒性作用而对健康细胞无影响,这对靶向癌症治疗策略具有重要意义。这种选择性不仅将对健康组织产生不良反应的风险降至最低,还提高了离子液体对抗癌症进展的治疗效果。

结论

这些发现为进一步探索SAILs作为治疗应用的潜在候选物铺平了道路,特别是在使用恶性肿瘤动物模型的肺癌治疗中。然而,在监管批准、生物相容性以及与药物的协同作用以确保患者安全方面的临床应用是必要的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ffe9/12120572/243eafb2992f/ao5c01250_0001.jpg

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