PMID- 20697773
OWN - NLM
STAT- MEDLINE
DCOM- 20120508
LR  - 20211020
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Linking)
VI  - 30
IP  - 1
DP  - 2012 Feb
TI  - Synthesis and antitumor activity of novel aroylthiourea derivatives of 
      podophyllotoxin.
PG  - 17-24
LID - 10.1007/s10637-010-9508-1 [doi]
AB  - A novel series of 4beta-[(4-substituted) aroylthiourea] derivatives of 
      podophyllotoxin were synthesized and their abilities to inhibit the growth of 
      cancer cells were investigated by MTT assay. Compound 4a possessed the highest 
      cytotoxicity on HepG2, A549 and HCT-116 cancer cell lines with the IC(50) values 
      of 0.1 muM. Apoptosis in HCT-116 cells induced by compound 4a was observed by 
      Hoechst33342-Propidium iodide (PI) and acridine orange (AO)-ethidium bromide (EB) 
      double staining assays. DNA flow cytometric analysis revealed that 4a induced 
      cell cycle arrest at G2/M phase and kDNA decatenation assay indicated that 4a 
      inhibited topoisomerase IIalpha-mediated kDNA decatenation. Our results indicated 
      that compound 4a possessed promising antitumor activity, which need to be studied 
      further.
FAU - Zhao, Yu
AU  - Zhao Y
AD  - Institute of Nautical Medicine, Nantong University, Nantong 226001, China.
FAU - Wang, Chengniu
AU  - Wang C
FAU - Wu, Zhonghua
AU  - Wu Z
FAU - Fang, Jinghuai
AU  - Fang J
FAU - Zhu, Li
AU  - Zhu L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100810
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (DNA, Catenated)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - EC 5.99.1.3 (DNA Topoisomerases, Type II)
RN  - GYV9AM2QAG (Thiourea)
RN  - L36H50F353 (Podophyllotoxin)
SB  - IM
MH  - Antigens, Neoplasm/metabolism
MH  - Antineoplastic Agents, Phytogenic/*chemical synthesis/*pharmacology
MH  - Apoptosis/drug effects
MH  - Cell Proliferation/*drug effects
MH  - DNA Topoisomerases, Type II/metabolism
MH  - DNA, Catenated/metabolism
MH  - DNA-Binding Proteins/antagonists & inhibitors/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/chemical synthesis/pharmacology
MH  - Flow Cytometry
MH  - G2 Phase Cell Cycle Checkpoints/drug effects
MH  - HCT116 Cells
MH  - Hep G2 Cells
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - M Phase Cell Cycle Checkpoints/drug effects
MH  - Molecular Structure
MH  - Podophyllotoxin/analogs & derivatives/*chemical synthesis/*pharmacology
MH  - Staining and Labeling
MH  - Structure-Activity Relationship
MH  - Thiourea/analogs & derivatives/*chemical synthesis/*pharmacology
MH  - Time Factors
EDAT- 2010/08/11 06:00
MHDA- 2012/05/09 06:00
CRDT- 2010/08/11 06:00
PHST- 2010/06/16 00:00 [received]
PHST- 2010/07/26 00:00 [accepted]
PHST- 2010/08/11 06:00 [entrez]
PHST- 2010/08/11 06:00 [pubmed]
PHST- 2012/05/09 06:00 [medline]
AID - 10.1007/s10637-010-9508-1 [doi]
PST - ppublish
SO  - Invest New Drugs. 2012 Feb;30(1):17-24. doi: 10.1007/s10637-010-9508-1. Epub 2010 
      Aug 10.