Rui-Xiang Ge, Jun-Zhuo Shi, Bin-Hao Guo, Meng-Jie Zhang, Min Zeng, Xiao-Rui An, Jing-Song Ye, Guo Cheng, Xin Fan, Meng-Wei Wang, Yun-Feng Zhou, Xi Li, Xiao-Bin Pang, Xin-Mei Xie, Hong-Da Zhang, Lu-Ling Zhao, Yang-Yang He, Jie-Jian Kou, Jing Ma, Yi Yan
Huaihe Hospital and Henan University. Fuwai Hospital and National Center for Cardiovascular Diseases. Shanghai Children’s Medical Center and Shanghai Jiao Tong University School of Medicine.
China
Journal of Medicinal Chemistry
J Med Chem 2026;
DOI: 10.1021/acs.jmedchem.5c02221
Abstract
Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive vascular remodeling and elevated pulmonary pressure, leading to right heart failure and high mortality, against which current treatments are limited and mechanisms remain incompletely understood. In this medicinal chemistry study, we designed, synthesized, and evaluated nine naphthalimide-polyamine derivatives (7a–7c, 12a–12b, 17a–17c and Subamnex) by taking advantage of the unique chemical structure and potential biological activity of polyamine derivatives. Our results demonstrate that the symmetrical polyamine azo-naphthalimide naphthalimide-polyamine derivatives, named Subamnex, suppresses pathological pulmonary arterial smooth muscle cells (PASMCs) proliferation and migration by targeting IL-6-induced STAT3 phosphorylation. By regulating key downstream effectors including NEAT1, Pim-1, and the Bax/Bcl-2 balance to attenuate remodeling, our work proposes a novel strategy to reverse vascular remodeling beyond symptom alleviation.
Category
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
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