Title:Dual Human Carbonic Anhydrase/Cyclooxygenase-2 Inhibitors: A Promising Approach for Cancer Treatment
Volume: 21
Issue: 16
Author(s): Mohammad Mahboubi-Rabbani and Afshin Zarghi*
Affiliation:
- Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran,Iran
Keywords:
Cancer, carbonic anhydrase, cyclooxygenase-2, dual enzyme inhibitors, Structure-Activity Relationships (SAR), sulfonamide.
Abstract: Human Carbonic Anhydrase (hCA) and Cyclooxygenase-2 (COX-2) have been known for a long to be
chiefly involved in both the pathogenesis and progression of cancer and cancer chemoresistance. Interestingly,
there is considerable evidence that the sulfonamide-type COX-2 selective inhibitors (coxibs) demonstrate
inhibitory action against the cancer-related hCA isoforms, confirmed by X-ray crystal structures for celecoxib
and valdecoxib complexes with the hCA active site. Consequently, the antineoplastic activity of the sulfonamide
coxibs may be justified by the contribution of hCA inhibition to such processes in addition to COX-2 inhibition.
Accordingly, these compounds' anti-tumoral activity should be further explored for their possible use in cancer
prevention and combination therapy; however, few papers deal with this issue. Beginning with a brief description
of the main molecular and catalytic features of both enzymes and their roles in tumor physiology, this review
covers a survey of the most recent evidence regarding the molecules targeting one or both of hCA and COX-2,
besides providing insights into their mechanism of action and efficacy in preventing cancer.
