Background: The function of Carbonic anhydrase is to facilitate the physiological process
i.e. interconversion of CO2 to HCO3
- by hydration. Carbonic anhydrase enzyme plays a vital role in different
physiological processes to regulate pH as well as regulate the inner environment of CO2 and secretion
Methods: Six representatives of amidophosphate derivatives (L1-L6) were synthesized and evaluated
for their biological activities against carbonic anhydrase enzyme.
Results: Out of six derivatives, L1 (IC50 = 12.5 ± 1.35 µM), and L2 (IC50 = 3.12 ± 0.45 µM) showed
potent activity against BCA-II. While (L3, L4 and L5) showed weak inhibitory activity with IC50 values
of 24.5 ± 2.25, 55.5± 1.60, and 75.5 ± 1.25 µM, respectively and were found to be weak inhibitors of
carbonic anhydrase as compared to acetazolamide (IC50 =0.12± 0.03µM), used as standard inhibitor.
A computational Petra/Osiris/Molinspiration/DFT (POM/DFT) based model has been expanded for the
determination of physicochemical parameters governing the bioactivity amidophosphate derivatives
(L1-L6) containing (O1 --- O2) pharmacophore site. The six compounds (L1-L6) analyzed here were
previously experimentally and now virtually screened for their anti-carbonic anhydrase activity.
Conclusion: The highest anti-carbonic anhydrase activity was obtained for compound L2, which exhibited
excellent bioactivity (% of inhibition = 95%), comparable to acetazolamide (% of inhibition =
89%). The compound L3 represents increased activity as compared to its analogues (L4-L6). The increase
of bioactivity from L3 to L4-L6 could be attributed to the presence of a minimum of steric effect
of substituents of P=O moiety which plays a decisive template part in the organization of anti-carbonic
anhydrase (O1---O2) phramacophore site. Moreover, it is inexpensive, has little side effects and possible
inclusions in selective anti-carbonic anhydrase agents design.