Dual Human Carbonic Anhydrase/Cyclooxygenase-2 Inhibitors: A Promising Approach for Cancer Treatment

Author(s):

Mohammad Mahboubi-Rabbani and Afshin Zarghi*   Pages 2163 - 2180 ( 18 )

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.

Keywords:

Cancer, carbonic anhydrase, cyclooxygenase-2, dual enzyme inhibitors, Structure-Activity Relationships (SAR), sulfonamide.

Affiliation:

Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran

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