Prof. Fang Wu’s group and Prof. Yegao Chen’s group identified new drug leads for Parkinson’s disease from Horsfieldia kingii

Parkinson’s disease (PD) is an age-related neurodegenerative disorder. As reported, Parkinson’s disease affects 2–3% of people aged ≥65 years. DOPA Decarboxylase (DDC) is a vitamin B₆-dependent enzyme, which has proven to be the target for methyldopa, a known drug for Parkinson’s disease. However, the weak affinity and specificity hamper the clinical application of methyldopa. Thus, the discovery of potent DDC-targeting inhibitor remains a focus of research in the development of therapeutic drugs for Parkinson’s disease.

Recently, Dr. Fang Wu’s group, from Shanghai Center for Systems Biomedicine of Shanghai Jiao Tong University, and Yegao Chen’s group, from School of Chemistry and Chemical Engineering of Yunnan Normal University, identified three new DDC inhibitors from Horsfieldia kingii. Compound (+)-1 is proved to be potent inhibitors of DDC (IC₅₀ = 35.1 ± 3.9 μM). This research will provide new strategies and drug leads for PD treatment. This work is another important progress after the joint work of Fang Wu’s group and Prof. Weidong Zhang’s group in finding natural DDC inhibitor from Euonymus glabra Roxb in 2014.  (ACS Chem. Biol. 2014 9(4):897-903).

The work has been accepted as journal article titled with “Horisfieldones A and B, Two Aromatic Ring-Contracted Dimeric Diarylpropanes with Human DOPA Decarboxylase Inhibitory Activity from Horsfieldia kingii” in Organic Letters (IF=6.49; Q1 Journal). Dr. Rui Zhan, lecturer of School of Chemistry and Chemical Engineering of Yunnan Normal University, Dr. Youtian Hu, research assistant professor of Shanghai Center for Systems Biomedicine of Shanghai Jiao Tong University, and Dr. Lidong Shao, lecturer of Department of Traditional Chinese Medicine of Yunnan Normal University, are the main author and co-first authors. Prof. Fang Wu and Prof. Yegao Chen are corresponding authors.