Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.15.1 (
ACE
)
18,300
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The sweeteners saccharin (
SAC
) and acesulfame K (
ACE
) recently entered the topic of anticancer human carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, as they showed to selectively inhibit the tumor-associated CAs IX/XII over ubiquitous CAs. A drug design strategy is here reported, which took
SAC
and
ACE
as leads and produced a series of 2
H
-benzo[
e
][1,2,4]thiadiazin-3(4
H
)-one-1,1-dioxides (
BTD
). Many derivatives showed greater potency (
K
I
s-CA IX 19.1-408.5 nM) and selectivity (II/IX SI 2-76) than the leads (
K
I
s-CA IX 103, 2400 nM; II/IX-SI 56, >4) against CA IX/XII over off-target isoforms. A thorough X-ray crystallographic study depicted their binding mode to both CA II and IX-mimic. The most representative
BTDs
were characterized in vitro for their antitumor activity against A549, PC-3, and HCT-116 cancer cell lines both in normoxia and hypoxia. The two most effective compounds were assayed for their effect on several apoptosis markers, identifying promising leads for the development of new anticancer drugs.
...
PMID:"A Sweet Combination": Developing Saccharin and Acesulfame K Structures for Selectively Targeting the Tumor-Associated Carbonic Anhydrases IX and XII. 3179 11
