Thiophene Derivatives as New Anticancer Agents and Their Therapeutic Delivery Using Folate Receptor-Targeting Nanocarriers

作者：Menghui Zhao, Yaxin Cui, Lang Zhao, Tianyu Zhu, Robert J. Lee, Wei‐Wei Liao, Fengying Sun, Youxin Li, Lesheng Teng · 发表于：ACS Omega · 年份：2019 · DOI：10.1021/acsomega.9b00554 · 被引用次数：33 · 研究领域：Nanoparticle-Based Drug Delivery、Synthesis and Characterization of Heterocyclic Compounds、Click Chemistry and Applications

High Resolution Image Download MS PowerPoint Slide A series of thiophene derivatives were synthesized by functionalization of 2,3-fused thiophene scaffolds. Their cytotoxicity was assessed against HeLa and Hep G2 cells. Compound 480 was identified as a promising candidate because of its low IC 50 in HeLa (12.61 μg/mL) and Hep G2 (33.42 μg/mL) cells. The drug was loaded into folic acid (FA)-coated nanoparticles (NPs) to address its poor water solubility and to improve its selectivity for cancer cells. Compound 480 was shown to induce apoptosis by changes in mitochondrial membrane potential (ΔΨ m ) and the reactive oxygen species level. Furthermore, FA-modified NPs enhanced uptake capacity compared to unmodified controls by flow cytometry. This drug delivered in folate nanocarriers is promising for the treatment of cancers.