Structure-activity relationship analysis of novel farnesyl transferase inhibitors

Farnesyltransferase (FTase) was selected as a target for virtual screening of inhibitors using the Glide v4.0 program in the Schrödinger software package. We discovered 13 novel structures as farnesyltransferase inhibitors (FTIs) with moderate potency. By analyzing the binding modes of representative compounds 8 (IC₅₀=2.29 μmol·L^-1) and 18 (IC₅₀=0.41 μmol·L^-1) with farnesyltransferase, it was found that compounds 8 and 18 didn't coordinate with Zn²⁺, indicating that the coordination between FTIs with Zn²⁺ is not essential for the bioactivity of the inhibitors. The structure-activity relationship was summarized by analyzing the predicted binding modes of representative compounds. It was found that the scaffolds of the discovered FTIs had room for structural optimization, which lay foundation for obtaining highly active and selective FTIs.