Review of the article „POM Analyses of Carbacylamidophosphates and Sulfanylamidophosphates Tested as New Carbonic Anhydrase Inhibitors“, verified by Publons, Web of Science

Abstract

Abstract: Six representatives of the amidophosphate derivatives (L1-L6) were synthesized and evaluated for their biological activities against carbonic anhydrase enzyme. Out of the six derivatives, L1 (IC50 = 12.5 ± 1.35 μM), and L2 (IC50 = 3.12 ± 0.45 μM) showed potent activity against BCA-II, whereas (L3, L4 and L5) showed weak inhibitory activity with the IC50 value of 24.5 ± 2.25, 24.5 ± 2.25, 55.5± 1.60, and 75.5 ± 1.25 μM respectively. They were found to be weak inhibitors of carbonic anhydrase as compared to acetazolamide (IC50 =0.12 ± 0.03 μM) which was used as standard inhibitor. All physic-chemical parameters were derived from the computational Petra/Osiris/Molinspiration/DFT (POM/DFT) model. They govern the bioactivity amidophosphate derivatives (L1-L6) which contain O,Opharmacophore site. The six compounds (L1-L6) analyzed here were previously screened experimentally and now screened virtually for their anti-carbonic anhydrase activity. The highest anti-carbonic anhydrase activity was obtained for compound L2 which exhibited excellent bioactivity (% inhibition = 95%) when compared to acetazolamide (% inhibition = 89%). The compound L3 represents an increased activity as compared to its analogues (L4- L6). The increase of bioactivity from L3 to L4-L6 could be attributed to the existence of minimum steric effect of substituents of P=O moiety which plays a crucial template role in the organization of anti-carbonic anhydrase O,O-phramacophore sites. Moreover, it is cheap, leading to fewer side effects and is possible to be included in selective anti-carbonic anhydrase agents design.