Kopsileuconines A-D: Bisindole alkaloids with cytotoxic activity from Kopsia hainanensis

Ni-Ping Li; Shan-Na Chen; Wei-Fang Su; Fen Liu; Lian-Jing Li; Jian-Guo Song; Min-Jing Cheng; Yi-Yi Li; Run-Qiang Chen; Xue-Ping Lei; Wen-Cai Ye; Lei Wang

doi:10.1016/j.phytochem.2024.114245

Kopsileuconines A-D: Bisindole alkaloids with cytotoxic activity from Kopsia hainanensis

Phytochemistry. 2024 Dec:228:114245. doi: 10.1016/j.phytochem.2024.114245. Epub 2024 Aug 10.

Authors

Ni-Ping Li¹, Shan-Na Chen¹, Wei-Fang Su¹, Fen Liu¹, Lian-Jing Li², Jian-Guo Song¹, Min-Jing Cheng¹, Yi-Yi Li¹, Run-Qiang Chen¹, Xue-Ping Lei³, Wen-Cai Ye⁴, Lei Wang⁵

Affiliations

¹ State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 510632, China; Center for Bioactive Natural Molecules and Innovative Drugs Research, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, China.
² Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China.
³ Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China. Electronic address: [email protected].
⁴ State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 510632, China; Center for Bioactive Natural Molecules and Innovative Drugs Research, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, China. Electronic address: [email protected].
⁵ State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 510632, China; Center for Bioactive Natural Molecules and Innovative Drugs Research, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, China. Electronic address: [email protected].

PMID: 39134110
DOI: 10.1016/j.phytochem.2024.114245

Abstract

Kopsileuconines A-D (1-4), four monoterpenoid bisindole alkaloids with unprecedented skeletons, along with their biosynthetically related precursors (5-8) were isolated from the roots of Kopsia hainanensis. Compound 1 possessed an undescribed C-6-C-5' dimerization pattern of aspidofractinine-type alkaloids. Compounds 2-4 were rhazinilam-kopsine (2) and rhazinilam-aspidofractinine type (3 and 4) bisindole alkaloids with undescribed skeletons, respectively. Their structures with absolute configurations were fully accomplished by extensive spectroscopic analysis, quantum-chemical calculations, and X-ray crystallography. A plausible biosynthetic pathway for 1-4 was proposed. Compound 2 exhibited a significant inhibitory effect against human lung cancer cell lines PC9 (EGFR mutant), with an IC₅₀ value of 15.07 ± 1.19 μM.

Keywords: Apocynaceae; Cytotoxic activity; Kopsia hainanensis; Monoterpenoid bisindole alkaloids; Structure elucidation.

MeSH terms

Antineoplastic Agents, Phytogenic* / chemistry
Antineoplastic Agents, Phytogenic* / isolation & purification
Antineoplastic Agents, Phytogenic* / pharmacology
Apocynaceae* / chemistry
Cell Line, Tumor
Cell Proliferation / drug effects
Crystallography, X-Ray
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor*
Humans
Indole Alkaloids* / chemistry
Indole Alkaloids* / isolation & purification
Indole Alkaloids* / pharmacology
Molecular Structure
Plant Roots / chemistry
Structure-Activity Relationship

Substances

Antineoplastic Agents, Phytogenic
Indole Alkaloids