PMID- 23300611
OWN - NLM
STAT- MEDLINE
DCOM- 20130717
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 12
DP  - 2012
TI  - Design, synthesis, and in vitro and in vivo biological studies of a 
      3'-deoxythymidine conjugate that potentially kills cancer cells selectively.
PG  - e52199
LID - 10.1371/journal.pone.0052199 [doi]
LID - e52199
AB  - Thymidine kinases (TKs) have been considered one of the potential targets for 
      anticancer therapeutic because of their elevated expressions in cancer cells. 
      However, nucleobase analogs targeting TKs have shown poor selective cytotoxicity 
      in cancer cells despite effective antiviral activity. 3'-Deoxythymidine 
      phenylquinoxaline conjugate (dT-QX) was designed as a novel nucleobase analog to 
      target TKs in cancer cells and block cell replication via conjugated DNA 
      intercalating quinoxaline moiety. In vitro cell screening showed that dT-QX 
      selectively kills a variety of cancer cells including liver carcinoma, breast 
      adenocarcinoma and brain glioma cells; whereas it had a low cytotoxicity in 
      normal cells such as normal human liver cells. The anticancer activity of dT-QX 
      was attributed to its selective inhibition of DNA synthesis resulting in 
      extensive mitochondrial superoxide stress in cancer cells. We demonstrate that 
      covalent linkage with 3'-deoxythymidine uniquely directed cytotoxic 
      phenylquinoxaline moiety more toward cancer cells than normal cells. Preliminary 
      mouse study with subcutaneous liver tumor model showed that dT-QX effectively 
      inhibited the growth of tumors. dT-QX is the first molecule of its kind with 
      highly amendable constituents that exhibits this selective cytotoxicity in cancer 
      cells.
FAU - Wei, Qiong
AU  - Wei Q
AD  - Institute of Materia Medica, College of Life Science and Technology, Huazhong 
      University of Science and Technology, Wuhan, Hubei, China.
FAU - Zhang, Dejun
AU  - Zhang D
FAU - Yao, Anna
AU  - Yao A
FAU - Mai, Liyi
AU  - Mai L
FAU - Zhang, Zhiwei
AU  - Zhang Z
FAU - Zhou, Qibing
AU  - Zhou Q
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121226
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Quinoxalines)
RN  - 11062-77-4 (Superoxides)
RN  - G34N38R2N1 (Bromodeoxyuridine)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/chemical synthesis/*pharmacology
MH  - Bromodeoxyuridine
MH  - Cell Proliferation/*drug effects
MH  - *Drug Design
MH  - Fluorescence
MH  - Humans
MH  - Liver/cytology/*drug effects
MH  - Liver Neoplasms, Experimental/drug therapy/*pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mitochondria/drug effects/metabolism
MH  - Molecular Structure
MH  - Neoplasms/drug therapy/*pathology
MH  - Quinoxalines/chemical synthesis/*pharmacology
MH  - Superoxides/metabolism
MH  - Thymidine/*analogs & derivatives/chemical synthesis/*chemistry/pharmacology
MH  - Tumor Cells, Cultured
PMC - PMC3530607
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/01/10 06:00
MHDA- 2013/07/19 06:00
PMCR- 2012/12/26
CRDT- 2013/01/10 06:00
PHST- 2012/08/02 00:00 [received]
PHST- 2012/11/12 00:00 [accepted]
PHST- 2013/01/10 06:00 [entrez]
PHST- 2013/01/10 06:00 [pubmed]
PHST- 2013/07/19 06:00 [medline]
PHST- 2012/12/26 00:00 [pmc-release]
AID - PONE-D-12-23110 [pii]
AID - 10.1371/journal.pone.0052199 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(12):e52199. doi: 10.1371/journal.pone.0052199. Epub 2012 Dec 26.