In silico evaluation of N-aryl-1,10-phenanthroline-2-amines as potential inhibitors of T. cruzi GP63 zinc-metalloprotease by docking and molecular dynamics simulations.

ABSTRACT: Based on the in vitro trypanocidal efficacy of previously synthesized N-aryl-1,10-phenanthroline-2-amines (Phen1-20) (aryl = R-phenyl, 1- or 2-naphthyl), we explored the potential interactions of these derivatives as ligands of our comparative model of T. cruzi GP63 (TcGP63). This surface metalloprotease plays a crucial role in parasite adhesion to host cells and aids in cell invasion during T. cruzi infection in Chagas disease. Ligand-protein consensus docking simulations using four GOLD scoring functions revealed that N-(R-phenyl) derivatives (R = CH₃, OCH₃, CF₃, CN, NO₂, F, Cl, and Br) presented poses with higher fitness scores than the N-naphthyl ones, with the six para-substituted derivatives (Phen4, p-CH₃; Phen7, p-OCH₃

SUBMITTER: Camargo PG 

PROVIDER: S-EPMC11839977 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature