Attaullah Hafiz Muhammad, Ejaz Syeda Abida, Channar Pervaiz Ali, Saeed Aamer, Ujan Rabail, Zargar Seema, Channar Sajid Ali, Sahito Reshma, Wani Tanveer A, Abbas Qamar
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan.
Department of Basic Sciences and Humanities, Faculty of Information Science and Humanities, Dawood University of Engineering and Technology, Karachi, 74800, Pakistan.
BMC Chem. 2024 Mar 6;18(1):47. doi: 10.1186/s13065-024-01149-8.
In the current study, Azo-Thiohydantoins derivatives were synthesized and characterized by using various spectroscopic techniques including FTIR, H-NMR, C-NMR, elemental and HRMS analysis. The compounds were evaluated for alkaline phosphatase activity and it was observed that among all the synthesized compounds, derivative 7e exhibited substantial inhibitory activity (IC = 0.308 ± 0.065 µM), surpassing the standard inhibitor (L-Phenyl alanine, IC = 80.2 ± 1.1 µM). Along with this, these derivatives were comprehensively examined regarding the electronic properties and reactivity of the synthesized compounds using Density Functional Theory (DFT) calculations, where the results were found very promising and the synthesized compound were found stable. After that, SwissADME evaluations highlighted compounds for their favorable physicochemical properties, including solubility and drug-likeness. Molecular docking exhibited the strong binding affinities of 7f and 7e derivatives with intestinal alkaline phosphatase (IAP), further supported by Molecular Dynamics (MD) simulations. This comprehensive integration of experimental and computational approaches sheds the light on the potential therapeutic applications of the synthesized compounds. By providing a detailed investigation of these aspects, this research opens the avenues for the development of novel pharmacologically active compounds with diverse applications.
在本研究中，合成了偶氮乙内酰脲衍生物，并通过多种光谱技术进行表征，包括傅里叶变换红外光谱（FTIR）、氢核磁共振（H-NMR）、碳核磁共振（C-NMR）、元素分析和高分辨率质谱（HRMS）分析。对这些化合物进行了碱性磷酸酶活性评估，结果发现，在所有合成化合物中，衍生物7e表现出显著的抑制活性（IC = 0.308 ± 0.065 μM），超过了标准抑制剂（L-苯丙氨酸，IC = 80.2 ± 1.1 μM）。与此同时，利用密度泛函理论（DFT）计算对这些衍生物的电子性质和合成化合物的反应活性进行了全面研究，结果很有前景，且合成化合物被发现是稳定的。之后，瑞士药物相似性评估（SwissADME）突出了这些化合物良好的物理化学性质，包括溶解性和类药性。分子对接显示7f和7e衍生物与肠道碱性磷酸酶（IAP）具有很强的结合亲和力，分子动力学（MD）模拟进一步证实了这一点。实验和计算方法的这种全面整合揭示了合成化合物潜在的治疗应用。通过对这些方面进行详细研究，本研究为开发具有多种应用的新型药理活性化合物开辟了道路。
