Cytotoxic clerodane diterpenoids from Croton crassifolius.
Hepatocellular carcinoma (HCC) is the most common type of liver cancer, and treatment options for HCC are limited. In addition, the discovery of new natural compounds with anti-hepatocarcinoma activity is attracting increasing attention. For this reason, phytochemical investigation of Croton crassifolius led to the isolation of 17 diterpenoids, including three new clerodane diterpenoids, named crassifolius A-C (1-3), along with 14 known ones (4-17). Their structures were established by 1D, 2D NMR, HR-ESI-MS, detailed calculated electronic circular dichroism (ECD) spectra and the assistance of quantum chemical predictions (QCP) of13C NMR chemical shifts. The cytotoxicities of all these compounds against human liver cancer lines (HepG2 and Hep3B) were determined. Among them, compound 1 exhibited good cytotoxicity with IC50value of 17.91μM against human liver tumor cells Hep3B. Following further studies of the anti-tumor mechanism of compound 1-induced cell growth inhibition, we found that compound 1 caused apoptotic cell death in Hep3B cells by detecting morphologic changes and Western blotting analysis.
Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Jin-Long
JL
Tian
Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Guo-Dong
GD
Yao
Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Yu-Xi
YX
Wang
College of Pharmaceutical and Biotechnology Engineering, Shenyang University of Chemical Technology, Shenyang 110142, PR China.
Pin-Yi
PY
Gao
Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Di
D
Wang
Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Ling-Zhi
LZ
Li
School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Bin
B
Lin
Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: xiaoxiao270@163.com.
Xiao-Xiao
XX
Huang
Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, PR China. Electronic address: songsj99@163.com.
Shao-Jiang
SJ
Song
D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D029802:Croton / Q000737:chemistry*; D045785:Diterpenes, Clerodane / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008113:Liver Neoplasms / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry
D045785:Diterpenes, Clerodane; D010936:Plant Extracts
Apoptosis; Croton crassifolius; Cytotoxicity; Hepatocellular carcinoma; Quantum-chemical predictions