Saeed Mohd, Shoaib Ambreen, Tasleem Munazzah, Al-Shammary Asma, Kausar Mohd Adnan, El Asmar Zeina, Abdelgadir Abdelmuhsin, Sulieman Abdel Moneim E, Ahmed Enas Haridy, Zahin Maryam, Ansari Irfan Ahmad
Department of Biology, College of Sciences, University of Ha'il, P.O. Box 2240, Ha'il 81451, Saudi Arabia.
Department of Clinical Pharmacy, College of Pharmacy, Jazan University, P.O. Box 114, Jazan 45142, Saudi Arabia.
ACS Omega. 2024 Aug 18;9(34):36099-36113. doi: 10.1021/acsomega.4c00082. eCollection 2024 Aug 27.
Alkannin is a plant-derived naphthoquinone that is isolated from the Boraginaceae family plants. In our previous studies, we found that shikonin, which is the -enantiomer of alkannin, has potent antidiabetic activity by inhibiting the action of the aldose reductase (AR) enzyme and the protein-tyrosine phosphatase 1B (PTP1B). Therefore, in this study, we aim to explore the antidiabetic effect of alkannin targeting PTP1B and AR by employing and techniques. For , we used different parameters such as ADMET analysis, molecular docking, MD simulation, Root Mean Square Deviation (RMSD), protein-ligand mapping, and free binding energy calculation. The evaluation was done by assessing the inhibitory activity and enzyme kinetics of PTP1B and AR inhibition by alkannin. The studies indicate that alkannin possesses favorable pharmacological properties and possesses strong binding affinity for diabetes target proteins. Hydrogen bonds (Val297, Ala299, Leu300, and Ser302) and hydrophobic interactions (Trp20, Val47, Tyr48, Trp79, Trp111, Phe122, Trp219, Val297, Cys298, Ala299, Leu300, and Leu301) are established by the compound, which potentially improves specificity and aids in the stabilization of the protein-ligand complex. The results from studies show a potent dose-dependent PTP1B inhibitory activity with an IC value of 19.47 μM, and toward AR it was estimated at 22.77 μM. Thus, from the results it is concluded that a low IC value of alkannin for both PTP1B and AR along with favorable pharmacological properties and optimal intra-molecular interactions indicates its utilization as a potential drug candidate for the management of diabetes and its end complications.
紫朱草素是一种从紫草科植物中分离出来的植物源萘醌。在我们之前的研究中，我们发现作为紫朱草素对映体的紫草素通过抑制醛糖还原酶（AR）和蛋白酪氨酸磷酸酶1B（PTP1B）的作用而具有强大的抗糖尿病活性。因此，在本研究中，我们旨在通过采用[具体技术名称1]和[具体技术名称2]技术来探索紫朱草素靶向PTP1B和AR的抗糖尿病作用。对于[技术应用方面]，我们使用了不同的参数，如ADMET分析、分子对接、分子动力学模拟、均方根偏差（RMSD）、蛋白质-配体映射和自由结合能计算。通过评估紫朱草素对PTP1B和AR的抑制活性以及酶动力学来进行[活性评估方面]评估。[实验研究方面]研究表明，紫朱草素具有良好的药理特性，并且对糖尿病靶蛋白具有很强的结合亲和力。该化合物形成了氢键（Val297、Ala299、Leu300和Ser302）和疏水相互作用（Trp20、Val47、Tyr48、Trp79、Trp111、Phe122、Trp219、Val297、Cys298、Ala299、Leu300和Leu301），这可能提高特异性并有助于蛋白质-配体复合物的稳定。[实验研究方面]研究结果显示，紫朱草素具有强大的剂量依赖性PTP1B抑制活性，IC值为19.47μM，对AR的抑制活性估计为22.77μM。因此，从结果可以得出结论，紫朱草素对PTP1B和AR的低IC值以及良好的药理特性和最佳的分子内相互作用表明其可作为治疗糖尿病及其并发症的潜在药物候选物。
