Work

Design, Synthesis, and Evaluation of Sodium Channel Blockers with Anti-invasive Activities in Medullary Thyroid Cancer

Year: 2025

Type: article

Abstract: This letter describes the structure–activity relationship studies of a voltage-gated sodium channel (VGSC) blocker SV188 guided by its docking model in the lacosamide binding site of Na V 1.7. Seventeen analogs of SV188 were designed, synthesized, and evaluated for whole cell I Na blockade and cytotoxicity using metastatic medullary thyroid cancer cell line MZ-CRC-1. Three analogs exhibited improved I Na blockade compared to SV188 . Thirteen analogs showed reduced cytotoxicity compared to SV188 . Three selected compounds were further evaluated for their cell invasion inhibition activities. All three compounds displayed cell invasion inhibitory activities that were better than those of SV188 . The most promising lead compound IIB7 showed no cytotoxicity to MZ-CRC-1 cells up to 100 μM and inhibited VGSC-mediated cell invasion by 71% at 15 μM.

Source: ACS Medicinal Chemistry Letters

DOI: 10.1021/acsmedchemlett.4c00576