Background: The over-expression of the carbonic anhydrases results in some specific
carcinomas including pancreatic, gastric and brain tumor. Tumors are distinguished under hypoxic
conditions and various investigations are being carried out to target the known hypoxic areas of the
tumors to increase the sensitivity towards standard therapeutic treatment.
Objective: Herein, we have designed and synthesized some biologically important esters, hydrazides,
thiocarbamates, 1,2,4-triazole-3-thiones and Schiff bases. The purpose of the research was to
evaluate the derivative against carbonic anhydrase and to assess the toxicity of the same compounds.
Method: The structures of all the compounds were characterized by FT-IR, mass spectrometry,
elemental analysis, 1H and 13C NMR spectroscopy. The synthetic derivatives were screened for
their inhibitory potential against carbonic anhydrase II by in vitro assay. Double reciprocal plots
for inhibition kinetics of the potent compounds were constructed and mode of inhibition was determined.
Furthermore, to check the cytotoxicity, these derivatives were tested against human
breast adenocarcinoma by MTT method.
Results: X-ray diffraction analysis of the compounds 10, 14 and 15 showed that they did not have
any π-π or C-H…π interactions. The experimental results were validated by molecular docking and
dynamic simulations of the potent compounds in the active pocket of enzyme. Important binding
interactions of potent compounds with the key residues in the active site of the carbonic anhydrase
enzyme were revealed. Drug likeness profile of the derivatives was evaluated to determine the
Conclusion: The proposed synthetic approach provides a suitable platform for the generation of a
new library of compounds which could potentially be employed in the future testing and optimization
of inhibitor potencies.