Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 61, Issue 23, Pages 10860-10874Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.8b01504
Keywords
-
Categories
Funding
- Ente Cassa di Risparmio di Firenze, Italy [ECR 2016.0774]
- National Center for Advancing Translational Sciences of the National Institutes of Health under University of Florida [TL1TR001428, UL1TR001427]
Ask authors/readers for more resources
Human carbonic anhydrases (CA, EC, 4.2.1.1) IX and XII are overexpressed in cancer cells as adaptive response to hypoxia and acidic conditions characteristic of many tumors. In addition, hypoxia facilitates the activity of specific oxido-reductases that may be exploited to selectively activate bioreductive prodrugs. Here, new selective CA IX/XII inhibitors, as analogues of the antitumor phase II drug SLC-0111 are described, namely ureido-substituted benzenesulfonamides appended with a nitro-aromatic moiety to yield an antiproliferative action increased by hypoxia. These compounds were screened for the inhibition of the ubiquitous hCA I/II and the target hCA IX/XII. Six X-ray crystallographies with CA II and IX/mimic allowed for the rationalization of the compounds inhibitory activity. The effects of some such compounds on the viability of HT-29, MDA-MB-231, and PC-3 human cancer cell lines in both normoxic and hypoxic conditions were examined, providing the initiation toward the development of hypoxia-activated antitumor CAIs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available