■乳腺癌细胞向远处转移,包括肺,肝脏,淋巴结,大脑和更多的人对患病个体的总体生存结果和无远处转移生存率产生了实质性影响。进行了几项临床前和临床研究以确定强力抑制剂的效力,但它们严重恶化了患者的生活质量。因此,迫切需要探索有效的自然疗法来对抗转移性乳腺癌。
筛选文献中记载的抗乳腺癌能力的阿育吠陀药用植物,并评价它们各自的活性部分对MMP9的抑制作用。使用分子对接确定植物化学物质的药物样功效,MD模拟,将ADMET和MM-PBSA进一步与合成类似物即强力霉素进行比较。
■在1000种植物化学物质中,12发挥甚至超过-9.0kcal/mol的最高结合亲和力(BA),这与表现出-7.3kcal/mol的BA的强力霉素相比显著更高。与37×30×37进行比较,在LYS104,ASP185,MET338,LEU39,ASN38的Viscosalactone展示了53×45×66的最佳结合位点,最高的BA。在MD模拟期间,粘酚内酯-MMP9复合物保持稳定20ns,动力学,观察到静电和势能优于强力霉素。此外,从Withaniasomnifera获得的Viscosalactone证明了Lipinski的5法则。
■获自睡眠乳杆菌的内服内酯可能是对抗转移性乳腺癌的有希望的候选药物。
UNASSIGNED: Metastasis of breast cancer cells to distant sites including lungs, liver, lymph node, brain and many more have substantially affected the overall survival outcome and distant metastasis free survival rate amongst the diseased individuals. Several pre-clinical and clinical studies were carried out to determine the potency of vigorous inhibitors but they extensively deteriorated the patient\'s quality of life. Hence, there exists an urgent need to explore potent natural remedy to fight against metastatic breast cancer.
UNASSIGNED: Ayurvedic medicinal plants documented in literature for their ability to fight against breast cancer was screened and their respective active moieties were evaluated to exert inhibitory effect against MMP9. Drug like efficacy of phytochemicals were determined using Molecular docking, MD Simulation, ADMET and MM-PBSA and were further compared with synthetic analogs i.e.
Doxycycline.
UNASSIGNED: Out of 1000 phytochemicals, 12 exerted highest binding affinity (BA) even more than -9.0 kcal/mol that was significantly higher in comparison to
Doxycycline which exhibited BA of -7.3 kcal/mol. In comparison to 37 × 30 × 37 Å, 53 × 45 × 66 Å offered best binding site and the highest BA was exhibited by Viscosalactone at LYS104, ASP185, MET338, LEU39, ASN38. During MD Simulation, Viscosalactone-MMP9 complex remained stable for 20 ns and the kinetic, electrostatic and potential energies were observed to be better than
Doxycycline. Furthermore, Viscosalactone obtained from Withania somnifera justified the Lipinski\'s Rule of 5.
UNASSIGNED: Viscosalactone obtained from W. somnifera may act as promising drug candidate to fight against metastatic breast cancer.