Lung cancer remains a leading cause of cancer-related mortality worldwide, with non-small cell lung carcinoma (NSCLC) representing the predominant subtype. Despite advances in targeted therapies, the development of potent and selective small-molecule therapeutics for NSCLC remains a key challenge in drug discovery. In this study, we designed and computationally evaluated a focused library of pyrazole-based derivatives as potential anticancer agents. A rational, multi-step in silico workflow integrating target prediction, molecular docking, and drug-likeness assessment was employed to identify promising candidates. Twelve pyrazole derivatives were docked against multiple NSCLC-relevant protein kinases, and their ADME properties were predicted using SwissADME webserver. Among these, PL-13 emerged as a lead candidate and was subsequently synthesized, structurally characterized, and evaluated in vitro. Cytotoxicity studies using the MTT assay demonstrated that PL-13 exhibits potent antiproliferative activity against A549 NSCLC cells while maintaining favorable selectivity over non-cancerous HFL-1 fibroblasts. These findings highlight pyrazole-based scaffolds as promising leads for NSCLC drug discovery and establish PL-13 as a valuable starting point for further SAR-driven optimization.

2022-12-05·Molecular pharmaceutics

Evaluation of Hepatoprotective Effects of Piperlongumine Derivative PL 1–3-Loaded Albumin Nanoparticles on Lipopolysaccharide/d-Galactosamine-Induced Acute Liver Injury in Mice

Article

作者: Yang, Jie ; Liu, Guoyun ; Guo, Xiaoyuan ; Li, Pengxiao ; Liu, Qing ; Liu, Ting

In recent years, piperlongumine (PL) having specific cytotoxicity has attracted considerable attention for anticancer activity. Through structural modification, the active derivative PL 1-3 shows potential anti-inflammatory activity and low cytotoxicity, but its water solubility is low. Here, PL 1-3-loaded bovine serum albumin nanoparticles (1-3 NPs) were prepared and characterized, which can improve the dissolution. 1-3 NPs exhibited effective hepatoprotective effects on lipopolysaccharide/d-galactosamine-induced acute liver injury of mice, which was similar to liver injury in clinical settings. 1-3 NPs treatment can inhibit inflammation, oxidative stress, and apoptosis via the downregulation of NF-κB signaling pathways, the activation of Nrf2/HO-1 signaling pathways, and the inhibition of expression of Bax and caspase 3 proteins. The above results demonstrated that PL 1-3-loaded bovine serum albumin nanoparticles possessed potential value in intervention of inflammation-based liver injury.

100 项与 PL-13 相关的药物交易

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