Citation: Jin-Yan Xie, Yu-Qi Gao, Wu-Yang Liu, Sheng-Yong Zhang, Ding Li, Wen-Ji Wang, Jiang-Jiang Tang, Jin-Ming Gao. Hypertaxoids A and B, two unique meroterpenoids from Hypericum elatoides as microtubule stabilizers and their antiproliferative effects on cervical cancer[J]. Chinese Chemical Letters, ;2026, 37(6): 111580. doi: 10.1016/j.cclet.2025.111580 shu

Hypertaxoids A and B, two unique meroterpenoids from Hypericum elatoides as microtubule stabilizers and their antiproliferative effects on cervical cancer

Jin-Yan Xie ^{a, 1} ,
Yu-Qi Gao ^{b, 1} ,
Wu-Yang Liu ^a ,
Sheng-Yong Zhang ^a ,
Ding Li ^a ,
Wen-Ji Wang ^a ,
Jiang-Jiang Tang ^{a, *,} ,
Jin-Ming Gao ^{a, *,}

a.
Shaanxi Key Laboratory of Natural Products and Chemical Biology, College of Chemistry and Pharmacy, Northwest A & F University, Yangling 712100, China
b.
College of Food Science and Technology, Northwest University, Xi'an 710069, China

tangjiang11@nwsuaf.edu.cn

jinminggao@nwsuaf.edu.cn

Received Date: 22 April 2025
Revised Date: 8 July 2025
Accepted Date: 10 July 2025
Available Online: 10 July 2025

Figures(4)

Hypertaxoids A (Hyp A, 1) and B (Hyp B, 2), two highly modified benzoyl polycyclic polyprenylated acylphloroglucinols (PPAPs) with an unprecedented carbon skeleton, were isolated from the aerial parts of Hypericum elatoides. Compounds 1 and 2 share a bicyclo[5.3.1]hendecane motif fused a 1,1-dimethylcyclohexane unit, with a taxoid-like 6/8/6 tricyclic core, while compound 1 possesses a new 6/8/6/5 tetracyclic ring system. Their structures were elucidated by a combination of nuclear magnetic resonance spectroscopy (NMR) analysis, high resolution electrospray ionization mass spectroscopy (HRESIMS), X-ray crystallography, and electronic circular dichroism (ECD) calculations. A key cation-anion progress in formation mechanism of 1 and 2 was revealed based on density functional theory (DFT) calculations. Among them, hypertaxoid B displayed selective inhibition on cell growth of human cervical cancer lines. The mechanism of action revealed that Hyp B could stabilize tubulin polymerization and disrupt the microtubule network, leading to apoptosis in C-33A cells through the mitochondria signaling pathway. Moreover, Hyp B significantly suppressed the C-33A tumor growth, brain metastasis, and angiogenesis in zebrafish xenograft models. Compound 2 represents the first tubulin polymerization-promoting natural product of PPAPs, which highlights it as a promising lead compound with a new type of skeleton for antineoplastic drug development for cervical cancer treatment.
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