Azmi Muhammad Bilal, Yu Han, Sohail Arisha, Asif Uzma, Ahmed Syed Danish Haseen, Qureshi Shamim Akhtar, Abdalla Mohnad
Computational Biochemistry Research Laboratory, Department of Biochemistry, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan.
Children's Hospital Affiliated to Shandong University, Jinan, China.
PLoS One. 2025 May 14;20(5):e0321687. doi: 10.1371/journal.pone.0321687. eCollection 2025.
Breast cancer is a major cause of death in women, and various drug therapies are used for its treatment. However, current therapies have many side effects and limitations. Propolis, a resinous product of bee hives, possesses a variety of biological activities, including anticancer and chemo-protective properties. The present study aimed to investigate the potential suitability of propolis-derived compounds to inhibit matriptase (MT-SP1), a potential protein target for breast cancer treatment, through comprehensive computational analysis. The MT-SP1 protein structure (PDB ID: 1EAX) was retrieved, energy-minimized, and validated. Five propolis-derived compounds with the highest binding energies to MT-SP1 were selected after virtual screening. Molecular docking of these selected ligands revealed binding energies ranging from -8.4 to -9.1 kcal/mol. Stable complex formation was validated by an additional 250 ns of molecular dynamics simulations. The HOMO-LUMO and DFT characteristics provided further evidence of the chemical reactivity and stability of these five ligands at the MT-SP1 active site. Screening of compounds for drug-likeness, pharmacokinetics (ADMET profiles), and toxicity identified two promising small molecules (PubChem IDs of ligands 72307 and 129827386) as potential drug candidates for inhibiting MT-SP1. However, experimental validation through in vitro or in vivo studies is necessary to confirm these computational findings and explore their therapeutic potential for breast cancer treatment.
乳腺癌是女性死亡的主要原因，目前有多种药物疗法用于治疗乳腺癌。然而，目前的疗法有许多副作用和局限性。蜂胶是蜂巢的一种树脂状产物，具有多种生物活性，包括抗癌和化学保护特性。本研究旨在通过全面的计算分析，研究蜂胶衍生化合物抑制matriptase（MT-SP1）的潜在适用性，MT-SP1是乳腺癌治疗的一个潜在蛋白质靶点。检索MT-SP1蛋白质结构（PDB ID：1EAX），进行能量最小化并验证。虚拟筛选后，选择了与MT-SP1结合能最高的五种蜂胶衍生化合物。这些选定配体的分子对接显示结合能范围为-8.4至-9.1千卡/摩尔。通过额外250纳秒的分子动力学模拟验证了稳定复合物的形成。HOMO-LUMO和DFT特性进一步证明了这五种配体在MT-SP1活性位点的化学反应性和稳定性。对化合物的类药性、药代动力学（ADMET谱）和毒性进行筛选，确定了两种有前景的小分子（配体72307和129827386的PubChem ID）作为抑制MT-SP1的潜在药物候选物。然而，需要通过体外或体内研究进行实验验证，以证实这些计算结果，并探索它们在乳腺癌治疗中的治疗潜力。
