Carbonic anhydrases (CAs, EC 22.214.171.124) catalyze the fundamental reaction of CO2 hydration
in all living organisms, being actively involved in the regulation of a plethora of
patho/physiological processes. They represent a typical example of enzyme convergent evolution,
as six genetically unrelated families of such enzymes were described so far. It is more than 70
years that synthetic compounds, mainly sulfonamides, have been used in clinical practice as diuretics and systemic acting antiglaucoma
drugs. Recent studies using natural product libraries and isolated constituents from natural sources (such as fungi and plants) have disclosed
novel chemotypes possessing carbonic anhydrase inhibition activities. These natural sources offer new opportunities in the search
for new and more effective carbonic anhydrase inhibitors, and may serve as new leads for the design and development of future drugs.
This review will discuss the most recent advances in the search of naturally occurring products and their synthetic derivatives that inhibit
the CAs and their mechanisms of action at molecular level. Plant extracts are not considered in the present review.