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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.

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