Imidazole-Functionalized Thieno[3,2-c]Quinoline Hybrids in Aggressive Medullary Thyroid Cancer Cell Models: Biological Evaluation and in Silico Insights

Background/Objectives: Medullary thyroid carcinoma (MTC) is a rare and aggressive endocrine malignancy frequently associated with RET alterations and dysregulation of RET-associated signaling pathways. In previous studies, first-generation nitro-substituted thieno[3,2-c]quinolines 1 showed promising antiproliferative activity in TT(RETC634R) cells, while subsequent imidazole-based optimization generated second-generation derivatives 2 with broad-spectrum antiproliferative activity in the NCI-60 human tumor cell line panel. Since thyroid cancer models are not included in the NCI-60 platform, the present study aimed to evaluate the antiproliferative potential of these optimized derivatives in clinically relevant MTC cellular models.