Introduction:
Carbonic anhydrases (CAs) are widespread metalloenzymes with the core function of
catalyzing the interconversion of CO2 and HCO3-. Targeting these enzymes using selective inhibitors has
emerged as a promising approach for the development of novel therapeutic agents against multiple diseases.
Method:
A series of novel thiosemicarbazones-containing derivatives were synthesized, characterized, and tested
for their inhibitory activity against pharmaceutically important human CA I (hCA I), II (hCA II), IX (hCA IX),
and XII (hCA XII) using the single tail approach.
Result:
The compounds generally inhibited the isoenzymes at low nanomolar concentrations, with compound 6b
having Ki values of 7.16, 0.31, 92.5, and 375 nM against hCA I, II, IX and XII, respectively. Compound 6e exhibited
Ki values of 27.6, 0.34, 872, and 94.5 nM against hCA I, II, IX and XII, respectively.
Conclusion:
To rationalize the inhibition data, molecular docking studies were conducted, providing insight into
the binding mechanisms, molecular interactions, and selectivity of the compounds towards the isoenzymes.