Synthesis, Density Functional Theory (DFT), Urease Inhibition and Antimicrobial Activities of 5-Aryl Thiophenes Bearing Sulphonylacetamide Moieties

Abstract

A variety of novel 5-aryl thiophenes 4a-g containing sulphonylacetamide (sulfacetamide) groups were synthesized in appreciable yields via Pd[0] Suzuki cross coupling reactions. The structures of these newly synthesized compounds were determined using spectral data and elemental analysis. Density functional theory (DFT) studies were performed using the B3LYP/6-31G (d, p) basis set to gain insight into their structural properties. Frontier molecular orbital (FMOs) analysis of all compounds 4a-g was computed at the same level of theory to get an idea about their kinetic stability. The molecular electrostatic potential (MEP) mapping over the entire stabilized geometries of the molecules indicated the reactive sites. First hyperpolarizability analysis (nonlinear optical response) were simulated at the B3LYP/6-31G (d, p) level of theory as well. The compounds were further evaluated for their promising antibacterial and anti-urease activities. In this case, the antibacterial activities were estimated by the agar well diffusion method, whereas the anti-urease activities of these compounds were determined using the indophenol method by quantifying the evolved ammonia produced. The results revealed that all the sulfacetamide derivatives displayed antibacterial activity against Bacillus subtiles, Escherichia coli, Staphylococcus aureus, Shigella dysenteriae, Salmonella typhae, Pseudomonas aeruginosa at various concentrations. Furthermore, the compound 4g N-((5-(4-chlorophenyl)thiophen-2-yl)sulfonyl) acetamide showed excellent urease inhibition with percentage inhibition activity~46.23˘0.11 at 15 µg/mL with IC 50 17.1 µg/mL. Moreover, some other compounds 4a-f also exhibited very good inhibition against urease enzyme.

A review on the development of urease inhibitors as antimicrobial agents against pathogenic bacteria

“…The authors observed a trend in which electron-withdrawing groups were more active at inhibiting the enzyme than their electron-donating counterparts, highlighting the di-halogenated compound ( 44 – Series A; Scheme 16 ) as the most active of the series [68] . Noreen et al also explored the potential of 5-aryl-thiophene-2-sulfonamides, three of which were more active than the positive control, namely compounds 48 and 49 ( Scheme 16 ) [69] .

Scheme 16 Chemical structures of urease inhbitors based on 5-aryl-thiophene-2-carbaldehydes scaffold.

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Sulfonamide-Linked Ciprofloxacin, Sulfadiazine and Amantadine Derivatives as a Novel Class of Inhibitors of Jack Bean Urease; Synthesis, Kinetic Mechanism and Molecular Docking

“…Among these are hydroxamic corrosive subordinates [ 17 ], hydroxyurea [ 18 ], hydroxamic acids [ 19 ], phosphorodiamidates, imidazoles, for example, rabeprazole, lansoprazole, omeprazole, quinines, thiol derivatives, and phenols, Schiff base and thiourea derivatives [ 20 ]. Sulfonamides constitute an important class of organic compounds that possess a broad spectrum of biological activities such as antibacterial, high-ceiling diuretic, hypoglycemic, antithyroid, anti-inflammatory and antiglaucoma effects [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. Noreen et al recently reported thiophene-tagged sulfonamides as µg/mL concentration urease inhibitors.…”

Features and Applications of Urine Stabilization Methods: A Review

“…In 2015, Mnaza Noreen used the indoxyl method to determine its inhibitory effect on the urease activity. The results showed that N- ((5-(4-chlorophenyl)thiophen-2-yl)sulfonyl) acetamide at a concentration of 15 µg/mL, IC 50 17.1 µg/mL has a good inhibitory effect on urease, and the inhibition rate is ∼46.23 ± 0.11% (Mnaza et al, 2015). Disulfiram and other compounds containing thiol reactive groups can be used to redesign better and more specific urease inhibitors (Díaz-Sánchez et al, 2016).…”