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 II.
Methods::
Quantification of the possible HITs was carried out by determining their IC50 values.
Results and Discussion::
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 atom 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, 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 hydroxyl group of phenyl ring.
Identification of small molecule inhibitor of cyclophilin-A using high throughput virtual screening and molecular docking Studies
