Density functional theory calculations in stereochemical determination of terpecurcumins J-W, cytotoxic terpene-conjugated curcuminoids from Curcuma longa L.
Fourteen novel terpene-conjugated curcuminoids, terpecurcumins J-W (1-14), have been isolated from the rhizomes of Curcuma longa L. Among them, terpecurcumins J-Q and V represent four unprecedented skeletons featuring an unusual core of hydrobenzannulated[6,6]-spiroketal (1 and 2), bicyclo[2.2.2]octene (3-7), bicyclo[3.1.3]octene (8), and spiroepoxide (13), respectively. The structures of compounds 1-14 were elucidated by extensive spectroscopic analysis, and their absolute configurations were established by electronic circular dichroism, vibrational circular dichroism, and (13)C NMR spectroscopic data analysis, together with density functional theory calculations. The structure and configuration of 1 was further confirmed by single-crystal X-ray diffraction (Cu Kα). The biogenetic pathways of 1-14 were proposed, involving Michael addition, condensation, Diels-Alder cycloaddition, and electrophilic substitution reactions. Terpecurcumins showed more potent cytotoxic activities than curcumin and ar-/β-turmerone. Among them, terpecurcumin Q (8) exhibited IC50 of 3.9 μM against MCF-7 human breast cancer cells, and mitochondria-mediated apoptosis played an important role in the overall growth inhibition. Finally, LC/MS/MS quantitative analysis of five representative terpecurcumins indicated these novel compounds were present in C. longa at parts per million level.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , 38 Xueyuan Road, Beijing 100191, China.
Xionghao
X
Lin
Shuai
S
Ji
Xue
X
Qiao
Hongbo
H
Hu
Ni
N
Chen
Yinhui
Y
Dong
Yun
Y
Huang
Dean
D
Guo
Pengfei
P
Tu
Min
M
Ye
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D030024:Curcuma / Q000737:chemistry*; D003474:Curcumin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D011789:Quantum Theory; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D053719:Tandem Mass Spectrometry; D013729:Terpenes / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D013729:Terpenes; D003474:Curcumin