Background: Structurally diverse organic compounds and available drugs were screened
against urease and carbonic anhydrase II in a formulation acceptable for high-throughput screening.
Objective: The study was conducted to find out potential inhibitors of urease and carbonic anhydrase
Methods: Quantification of the possible HITs was carried out by determining their IC50 values.
Results: The results of several screened compounds, including derivatives of oxadiazole, coumarins,
chromane-2, 4-diones and metal complexes of cysteine-omeprazole showed promising inhibitory
activities with IC50 ranging from 47 μM to 412 μM against the urease. The interactions of active
compounds with active sites of enzymes were investigated through molecular docking studies
which revealed that (R)-1-(4-amino-4-(5-(thiophen-2-yl)-1,3,4-oxadiazol-2-yl) butyl) guanidine
possessing IC50 of 47 μM interacts with one of the nickel metal atoms of urease besides further
interactions as predictable hydrogen bonds with KCX490, Asp633, His492, His407 and His409
along with Ala440 and 636. Bi-ligand metal complexes of 4-aminoantipyrine based Schiff bases
showed activation of urease with AC50 ranging from 68 μM to 112 μM. Almost 21 compounds with
varying functional groups including pyrimidines, oxadiazoles, imidazoles, hydrazides and tin based
compounds were active carbonic anhydrase II inhibitors presenting 98 μM to 390 μM IC50 values.
Several N-substituted sulfonamide derivatives were inactive against carbonic anhydrase II.
Conclusion: Among all the screened compounds, the highly active inhibitor of carbonic anhydrase
II was (4-(3-hydroxyphenyl)-6-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)phenyl) methanone
with IC50 of 98.0 μM. This particular compound showed metallic interaction with Zn ion of
carbonic anhydrase II through the hydroxyl group of the phenyl ring.