黃雯華黃旭山Maryam Rachmawati Sumitra2026-05-062026-05-062025-05-29https://203.71.86.71/handle/123456789/9471學位別：博士 口試委員：李世裕; 吳駿翃; 林宏惲; 黃旭山; 黃雯華 關鍵字：槲皮素、喹唑啉、KRAS、非小細胞肺癌、小分子抑制劑、分子對接、分子動力學Quercetin and quinazoline are well-known bioactive scaffolds with anticancer properties. In this study, we designed, synthesized, and evaluated 44 novel hybrid compounds combining quercetin and quinazoline structures to target KRAS-driven non-small cell lung cancer (NSCLC). All compounds were structurally confirmed via NMR and MS. Biological activities were assessed across NSCLC cell lines (H1299, H1975, H441, and A549) using sulforhodamine B (SRB) assays, along with colony formation, migration, and sphere formation assays. Among them, compound 15 exhibited the most potent and consistent activity, with IC₅₀ values in the low micromolar range. Western blot and RNA sequencing analysis revealed that compound 15 selectively downregulated key components of the PI3K/mTOR pathway, without significantly affecting RAF/MAPK signaling. Molecular docking indicated strong binding affinity with KRAS, while molecular dynamics simulations confirmed stable interactions (RMSD < 2.5 Å) and minimal fluctuations at the binding interface (low RMSF). These results suggest that compound 15 is a promising candidate for targeting KRAS-mediated signaling in NSCLC.系所名稱：癌症生物學與藥物研發博士學位學程thesis