Abstract
Sulfonamide derivatives serve as an important building blocks in the drug design discovery and development (4D) process. Ciprofloxacin-, sulfadiazine- and amantadine-based sulfonamides were synthesized as potent inhibitors of jack bean urease and free radical scavengers. Molecular diversity was explored and electronic factors were also examined. All 24 synthesized compounds exhibited excellent potential against urease enzyme. Compound 3e (IC50 = 0.081 ± 0.003 µM), 6a (IC50 = 0.0022 ± 0.0002 µM), 9e (IC50 = 0.0250 ± 0.0007 µM) and 12d (IC50 = 0.0266 ± 0.0021 µM) were found to be the lead compounds compared to standard (thiourea, IC50 = 17.814 ± 0.096 µM). Molecular docking studies were performed to delineate the binding affinity of the molecules and a kinetic mechanism of enzyme inhibition was propounded. Compounds 3e, 6a and 12d exhibited a mixed type of inhibition, while derivative 9e revealed a non-competitive mode of inhibition. Compounds 12a, 12b, 12d, 12e and 12f showed excellent radical scavenging potency in comparison to the reference drug vitamin C.
Highlights
Ureases (EC 3.5.1.5; urea amidohydrolase) belong to a super group of amidohydrolases and phosphotriestreases, heteropolymeric enzymes with the dynamic site containing two nickel (II) atoms, found in extensive amounts in nature among plants, microbes, organisms, green growth and spineless creatures [1,2,3]
12a–f against the targeted protein, their generated docked complexes were analyzed on the basis and 12a–f against the targeted protein, their generated docked complexes were analyzed on the basis of of minimum minimum energy energy values values (Kcal/mol)
A small library of compounds based on drug derivatives was synthesized using substituted sulphonyl chlorides
Summary
Ureases (EC 3.5.1.5; urea amidohydrolase) belong to a super group of amidohydrolases and phosphotriestreases, heteropolymeric enzymes with the dynamic site containing two nickel (II) atoms, found in extensive amounts in nature among plants, microbes, organisms, green growth and spineless creatures [1,2,3]. Urease-delivering microscopic organisms have harmful effects on human health. In human beings the ureas of Helicobacter pylori cause afflictions of the gastrointestinal and urinary tract, for example, stomach disease and peptic ulcers [4,5]. The dynamic focus of urease is relied on trapping three water molecules and a hydroxide ion connects between two nickel. Molecules 2017, 22, 1352; doi:10.3390/molecules22081352 www.mdpi.com/journal/molecules atoms [8]. Urea possesses two binding sites and is capable of forming hydrogen bonding linkages
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