Ishaq Saqib, Habib Obaid, Aziz Abdul, Tahir Raheel, Mushtaq Hira, Hassan Said, Sarwar Sarah, Mubarak Mohammad S, Ahmad Ajaz, Ullah Amin
Guangdong Provincial Key Laboratory of System Biology and Synthetics Biology for Urogenital Tumors, School of Basic Medicine, Shenzhen University Medical School, Shenzhen University (SZU), Guangdong, China.
Department of Computer Sciences and Bioinformatics, Khushal Khan Khattak University, Karak, Khyber Pakhtunkhwa, Pakistan.
Heliyon. 2025 Jan 10;11(2):e41739. doi: 10.1016/j.heliyon.2025.e41739. eCollection 2025 Jan 30.
Fluorinated phospholipid analogs Edelfosine and Ilmofosine drug reveal expressive potential as antineoplastic factors though targeted interaction with heat shock protein (HSP70KDa1A), an essential mediator in cancer pathophysiology. Using evolved computational approaches, this research evaluated their ADMET (absorption, distribution, metabolism, excretion and toxicity) profiles receptor binding affinities and molecular dynamics. Molecular docking discernible vigorous interactions with Edelfosine drug displaying greater binding stability and consistent hydrogen bonding as confirmed by 100 ns molecular dynamics simulations. Comparative interpretation emphasized Edelfosine drug enhanced pharmacokinetic properties depicted by lower RMSD values, stable solvent-accessible surface area and reduced structural fluctuations relative to Ilmofosine drug. Functional annotation and phylogenetic investigation affirmed the evolutionary conservation and pivotal biological function of heat shock protein (HSP70KDa1A). These findings position Edelfosine drug as a promising candidate for targeted cancer therapy appropriated further experimental validation to elucidate its mechanisms of action and therapeutic efficacy.
氟化磷脂类似物依地福新和 ilmofosine 药物通过与热休克蛋白（HSP70KDa1A）的靶向相互作用显示出作为抗肿瘤因子的显著潜力，热休克蛋白是癌症病理生理学中的一种重要介质。本研究采用进化计算方法，评估了它们的 ADMET（吸收、分布、代谢、排泄和毒性）概况、受体结合亲和力和分子动力学。分子对接显示依地福新药物有强烈的相互作用，表现出更高的结合稳定性和一致的氢键，这在 100 纳秒的分子动力学模拟中得到了证实。比较分析强调，与 ilmofosine 药物相比，依地福新药物的药代动力学特性得到增强，表现为更低的均方根偏差值、稳定的溶剂可及表面积和减少的结构波动。功能注释和系统发育研究证实了热休克蛋白（HSP70KDa1A）的进化保守性和关键生物学功能。这些发现使依地福新药物成为靶向癌症治疗的有希望的候选药物，需要进一步的实验验证来阐明其作用机制和治疗效果。
