Naphthoquinones from Catalpa bungei "Jinsi" as potent antiproliferation agents inducing DNA damage

Ye Qin; Shan Liu; Qun Zou; Xiaorong Cai; Zhiyong Guo; Lingling Yu; Junhui Wang; Zhangshuang Deng

doi:10.1016/j.fitote.2022.105196

Naphthoquinones from Catalpa bungei "Jinsi" as potent antiproliferation agents inducing DNA damage

Fitoterapia. 2022 Jul:160:105196. doi: 10.1016/j.fitote.2022.105196. Epub 2022 Apr 12.

Authors

Ye Qin¹, Shan Liu², Qun Zou³, Xiaorong Cai⁴, Zhiyong Guo³, Lingling Yu⁵, Junhui Wang⁶, Zhangshuang Deng⁷

Affiliations

¹ Key Laboratory of Functional Yeast, China National Light Industry & Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, China; Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, Three Gorges University Medical College, China Three Gorges University, Yichang 443002, China.
² Key Laboratory of Functional Yeast, China National Light Industry & Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, China; Songzi Center for Inspection and Test, Songzi 434200, China.
³ Key Laboratory of Functional Yeast, China National Light Industry & Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, China.
⁴ Three Gorges Public Inspection and Testing Center, Yichang 443005, China.
⁵ Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, Three Gorges University Medical College, China Three Gorges University, Yichang 443002, China.
⁶ State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of Tree Breeding and Cultivation of State Forestry Administration, Research Institute of Forestry, Chinese Academy of Forestry, Beijing 100091, China. Electronic address: wangjh@caf.ac.cn.
⁷ Key Laboratory of Functional Yeast, China National Light Industry & Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, China. Electronic address: dzs163@163.com.

PMID: 35427755
DOI: 10.1016/j.fitote.2022.105196

Abstract

Structure-guided isolation of a CH₂Cl₂-soluble fraction of the heartwood of Catalpa bungei "Jinsi" provided two new naphthoquinones, 9-hydroxy-4-oxo-α-lapachone (1) and 6-hydroxy-4-oxo-α-lapachone (2), together with three undescribed ones (3-5) and six known ones (6-11). The structures were elucidated on the basis of spectroscopic methods including electronic circular dichroism calculation. The antiproliferative effects of these isolates were evaluated in human breast adenocarcinoma cells MCF7. (4R)-4,9-dihydroxy-α-lapachone (5) and (4S)-4,9-dihydroxy-α-lapachone (6) exhibited the significant activities with IC₅₀ values of 2.19 and 2.41 μM, respectively. The structure-activity relationship of 1-11 in the antiproliferative assay was then discussed. The most potent 5 and 6 were found to induce cell arrest in G1 phage through DNA damage. The findings provided some valuable insights for the discovery and structural modification of α-lapachone as antiproliferative lead compounds against human breast adenocarcinoma cells.

Keywords: Antiproliferative activity; Catalpa bungei “Jinsi”; DNA damage; Naphthoquinone; α-Lapachone.

MeSH terms

Adenocarcinoma*
Bignoniaceae* / chemistry
DNA Damage
Humans
Molecular Structure
Naphthoquinones* / chemistry
Naphthoquinones* / pharmacology

Substances

Naphthoquinones