Citation: Ji-Hui Zhang, Hui-Lin Ou, Ting Lu, Si-Yu Yang, Ding Luo, Peng Wu, Yao-Lan Li, Neng-Hua Chen, Guo-Cai Wang, Yu-Bo Zhang. Daphcalycines A–D, four highly rearranged Daphniphyllum alkaloids with cardioprotective activity from Daphniphyllum calycinum[J]. Chinese Chemical Letters, ;2026, 37(3): 111314. doi: 10.1016/j.cclet.2025.111314 shu

Daphcalycines A–D, four highly rearranged Daphniphyllum alkaloids with cardioprotective activity from Daphniphyllum calycinum

Ji-Hui Zhang ^a ,
Hui-Lin Ou ^a ,
Ting Lu ^a ,
Si-Yu Yang ^c ,
Ding Luo ^a ,
Peng Wu ^d ,
Yao-Lan Li ^a ,
Neng-Hua Chen ^{b, *,} ,
Guo-Cai Wang ^{a, *,} ,
Yu-Bo Zhang ^{a, c, *,}

a.
State Key Laboratory of Bioactive Molecules and Druggability Assessment, and Department of Pharmacology, School of Medicine, Jinan University, Guangzhou 510632, China
b.
Department of Pharmacy, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China
c.
Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China
d.
Guangdong Provincial Key Laboratory of Translational Cancer Research of Chinese Medicines, Joint International Research Laboratory of Translational Cancer Research of Chinese Medicines, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

chennengflo@163.com

twangguocai@jnu.edu.cn

ybzhang99@126.com

Received Date: 5 January 2025
Revised Date: 10 May 2025
Accepted Date: 13 May 2025
Available Online: 13 May 2025

Figures(5)

Four novel Daphniphyllum alkaloids with highly rearranged skeletons involving a 6/5/7/7/5 pentacyclic scaffold (1), a 6/5/7/5/6/5/6 heptacyclic scaffold (2 and 4), and a 6/5/7/5/6/5 hexacyclic scaffold (3), were isolated from Daphniphyllum calycinum. Particularly, compound 1 contains a unique 13-oxa-17-aza-pentacyclo[7.6.4.1^12,15.0^4,8.0^9,15] eicosane core. Their structures were elucidated by comprehensive spectroscopic analyses, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Putative biosynthetic pathways for compounds 1–4 were discussed with caldaphnidine C (5) as their biosynthetic precursor. Compound 2 markedly enhanced the survival of H9c2 cardiomyocytes under oxygen glucose deprivation and reoxygenation conditions. Mechanistic study revealed that 2 exerted its cardioprotective effects by activating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) antioxidant pathway, thereby enhancing cellular antioxidant capacity and alleviating oxidative stress induced by hypoxia.
- Daphniphyllum calycinum,
- Daphniphyllum alkaloid,
- Biosynthetic pathway,
- Cardioprotective activity,
- Keap1-Nrf2/HO-1 pathway
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