Aotaphenazine, a rare hydrophenazine, targets topoisomerase II with anticancer efficacy: In silico to in vitro evidence.

ABSTRACT:

Background

Topoisomerase II (Topo II) remains a validated target for anticancer therapy, with many clinically used agents acting via DNA intercalation and enzyme inhibition. However, their clinical use is limited by severe toxicity and resistance. In this study, we investigate aotaphenazine, a rare hydrophenazine derivative isolated from Streptomyces sp. IFM 11694 as a potential novel Topo II inhibitor with selective anticancer activity.

Methods

Molecular docking and 400 ns molecular dynamics (MD) simulations were employed to evaluate aotaphenazine's binding mode within the DNA-Topo II complex (PDB: 3QX3). MM-GBSA calculations quantified interaction energetics, while ProLIF and PLIP analyses detailed the interaction patterns. Topo II inhibition was assessed via in vitro enzy

SUBMITTER: Metwaly AM 

PROVIDER: S-EPMC12680189 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature