110570-07-5Relevant articles and documents
Structural investigations on coumarins leading to chromeno[4,3-c]pyrazol-4-ones and pyrano[4,3-c]pyrazol-4-ones: New scaffolds for the design of the tumor-associated carbonic anhydrase isoforms IX and XII
Bonardi, Alessandro,Falsini, Matteo,Catarzi, Daniela,Varano, Flavia,Di Cesare Mannelli, Lorenzo,Tenci, Barbara,Ghelardini, Carla,Angeli, Andrea,Supuran, Claudiu T.,Colotta, Vittoria
, p. 47 - 59 (2018/02/09)
Human carbonic anhydrases (hCAs, EC 4.2.1.1) IX and XII are overexpressed in a wide variety of cancers and are considered available drug targets for anti-tumor therapy since their inhibition has been shown to reduce tumor growth and metastasis. A set of coumarin derivatives (1–10) and several 1-aryl and 2-aryl-substituted chromeno[4,3-c]pyrazol-4-ones (11–37) and pyrano[4,3-c]pyrazol-4-ones (38–39) were synthesized and tested against the tumor-associated hCAs IX and XII and the cytosolic isoforms hCAs I and II. Several compounds were potent (Ki i = 5.6–9.6 nM), while none were effective against the off-target cytosolic hCAs I and II. Some selected inhibitors (6, 11, 13, 19, 21, 25, 31 and 39) showed activity as antiproliferative agents on HT-29 colon cancer cell lines both in normoxic and hypoxic conditions. This finding led us to hypothesize for these derivatives more than one mechanism of action, involving hCAs IX and XII inhibition in hypoxia and other not identified target(s) in normoxia.
