PMID- 23300615
OWN - NLM
STAT- MEDLINE
DCOM- 20130702
LR  - 20220331
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 12
DP  - 2012
TI  - In vitro evaluation of ESE-15-ol, an estradiol analogue with nanomolar 
      antimitotic and carbonic anhydrase inhibitory activity.
PG  - e52205
LID - 10.1371/journal.pone.0052205 [doi]
LID - e52205
AB  - Antimitotic compounds are still one of the most widely used chemotherapeutic 
      anticancer drugs in the clinic today. Given their effectiveness against cancer it 
      is beneficial to continue enhancing these drugs. One way is to improve the 
      bioavailability and efficacy by synthesizing derivatives that reversibly bind to 
      carbonic anhydrase II (CAII) in red blood cells followed by a slow release into 
      the blood circulation system. In the present study we describe the in vitro 
      biological activity of a reduced derivative of 2-ethyl-3-O-sulphamoyl-estradiol 
      (2EE), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol). 
      ESE-15-ol is capable of inhibiting carbonic anhydrase activity in the nanomolar 
      range and is selective towards a mimic of carbonic anhydrase IX when compared to 
      the CAII isoform. Docking studies using Autodock Vina suggest that the 
      dehydration of the D-ring plays a role towards the selectivity of ESE-15-ol to 
      CAIX and that the binding mode of ESE-15-ol is substantially different when 
      compared to 2EE. ESE-15-ol is able to reduce cell growth to 50% after 48 h at 
      50-75 nM in MCF-7, MDA-MB-231, and MCF-12A cells. The compound is the least 
      potent against the non-tumorigenic MCF-12A cells. In vitro mechanistic studies 
      demonstrate that the newly synthesized compound induces mitochondrial membrane 
      depolarization, abrogates the phosphorylation status of Bcl-2 and affects gene 
      expression of genes associated with cell death and mitosis.
FAU - Stander, Barend Andre
AU  - Stander BA
AD  - Department of Physiology, University of Pretoria, Pretoria, Gauteng, South 
      Africa. standerandre@gmail.com
FAU - Joubert, Fourie
AU  - Joubert F
FAU - Tu, Chingkuang
AU  - Tu C
FAU - Sippel, Katherine H
AU  - Sippel KH
FAU - McKenna, Robert
AU  - McKenna R
FAU - Joubert, Annie Margaretha
AU  - Joubert AM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121227
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol)
RN  - 0 (Antimitotic Agents)
RN  - 0 (Carbonic Anhydrase Inhibitors)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Sulfonamides)
RN  - 0 (Tubulin)
RN  - 452VLY9402 (Serine)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 4.2.1.1 (Carbonic Anhydrases)
SB  - IM
MH  - Antimitotic Agents/chemistry/metabolism/*pharmacology
MH  - Carbonic Anhydrase Inhibitors/chemistry/metabolism/*pharmacology
MH  - Carbonic Anhydrases/chemistry/*metabolism
MH  - Cell Cycle/drug effects
MH  - Cell Proliferation/drug effects
MH  - Estradiol/*analogs & derivatives/metabolism/*pharmacology
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - MCF-7 Cells
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Molecular Docking Simulation
MH  - Neoplasm Metastasis
MH  - Phosphorylation/drug effects
MH  - Protein Conformation
MH  - Proto-Oncogene Proteins c-bcl-2/chemistry/metabolism
MH  - Serine/metabolism
MH  - Sulfonamides/*metabolism/*pharmacology
MH  - Tubulin/chemistry/metabolism
PMC - PMC3531393
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/01/10 06:00
MHDA- 2013/07/03 06:00
PMCR- 2012/12/27
CRDT- 2013/01/10 06:00
PHST- 2012/05/20 00:00 [received]
PHST- 2012/11/14 00:00 [accepted]
PHST- 2013/01/10 06:00 [entrez]
PHST- 2013/01/10 06:00 [pubmed]
PHST- 2013/07/03 06:00 [medline]
PHST- 2012/12/27 00:00 [pmc-release]
AID - PONE-D-12-14601 [pii]
AID - 10.1371/journal.pone.0052205 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(12):e52205. doi: 10.1371/journal.pone.0052205. Epub 2012 Dec 27.