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.
ABSTRACT
4,21-Secovincanol (1), a novel C-21/N-4 cleavage monoterpenoid indole alkaloid, along with four analogs (2-5), were obtained from the aerial parts of Kopsia hainanensis. Structurally, compound 1 might be a derivative of epivincanol (2) via C-21/N-4 cleavage. Their structures were confirmed by means of comprehensive spectroscopic data analysis and comparison with the reported data. All isolates significantly inhibited Con A-stimulated mice splenocytes proliferation at 10-40â µM in a dose-dependent manner inâ vitro. Especially, compound 3 exhibited potent activities comparable to positive control (Dexamethasone, DXM).
Subject(s)
Apocynaceae/chemistry , Immunosuppressive Agents/pharmacology , Plant Extracts/pharmacology , Spleen/drug effects , Animals , Cell Proliferation/drug effects , Concanavalin A/antagonists & inhibitors , Concanavalin A/pharmacology , Dose-Response Relationship, Drug , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/isolation & purification , Mice , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/isolation & purificationABSTRACT
The ethanol extract of the twigs and leaves of Kopsia hainanensis afforded six new aspidofractinine alkaloids, kopsiahainanins A-F (1-6), among which alkaloids 1 and 2 possessed a lactone bridge with novel regiochemistry. The structures of the isolated compounds were established based on 1D and 2D (1H1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated compounds were tested in vitro for cytotoxic activity against seven tumor cell lines and antibacterial activities against two Gram-positive bacteria and five Gram-negative bacteria. As a result, alkaloids 1 and 2 exhibited cytotoxic activities (IC50 values <20⯵M) against all tested tumor cell lines and significant antibacterial properties (MIC values from 0.12 to 0.26â¯mM).
Subject(s)
Anti-Bacterial Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Apocynaceae/chemistry , Indole Alkaloids/pharmacology , Anti-Bacterial Agents/isolation & purification , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , China , Humans , Indole Alkaloids/isolation & purification , Microbial Sensitivity Tests , Molecular Structure , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Components, Aerial/chemistry , Plant Extracts/chemistryABSTRACT
Five new aspidofractinine-type alkaloids, kopsiahainins A-E (1-5), were isolated from a 80% EtOH extract of the leaves and stems of Kopsia hainanensis. Structural elucidation of all the compounds were performed by spectral methods such as 1D- and 2D-NMR, IR, UV, and HR-ESI-MS. Alkaloids 3 and 4 exhibited some cytotoxic activity against all of six tested tumor cell lines (BGC-823, HepG2, MCF-7, SGC-7901, SK-MEL-2, and SK-OV-3) with IC50 values of 7.3-9.5µM and 9.2-10.6µM, respectively.