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 IC50 17.1 µg/mL. Moreover, some other compounds 4a–f also exhibited very good inhibition against urease enzyme.
Highlights
N-acylsulfonamide is well known basic common structural motif [1], which is present as a functional group in a wide range of therapeutics [2]
Kulsoom et al reported that sulfacetamides are effective against different Escherichia coli and Staphylococcus aureus strains and sulfacetamide suspension can be used for the treatment of eye infections caused by Staphylococcus aureus [24]
We have reported the synthesis of 5-aryl thiophenes sulphonylacetamide derivatives through Pd[0] catalyzed Suzuki cross coupling reactions of 5-bromothiophene acylsulfonamide with various aryl boronic acids/esters under mild conditions
Summary
N-acylsulfonamide (sulfacetamide) is well known basic common structural motif [1], which is present as a functional group in a wide range of therapeutics [2]. The Suzuki reaction of N-((5-bromothiophen-2yMl)osleuclufloesn2y0l1)5a,c2e0t,a1m99i1d4e–1(939,208 .704 mmol) with 0.774 mmol of different aryl boronic acids and boronic esters gave 5-arylthiophene-2-sulfonylacetamides 4a–g in moderate to very good yields (Table 1) [13]. The Pd[0] catalyzed reaction of N-((5-bromothiophen-2-yl)sulfonyl)acetamide (3, 0.704 mmol) with similar phenyl boronic esters (0.774 mmol) in toluene-water (4:1 solvent/water ratio) at 90 ̋C for 30 h in the presence of Pd (PPh3) (5 mol %) as a catalyst, to afford a moderate yield (64%, Table 1) of the desired product 4a. It was noted that Pd[0] Suzuki cross coupling reactions of 3 with 3,5-methyl-ditrifluoromethylphenyl boronic ester, 3,4-dichlorophenyl boronic acid and 4-chlorophenyl boronic acid (0.774 mmol) afforded the desired compounds 4b, 4c and 4g in 66%, 68% and 65% yields, respectively (Table 1). The 1H-NMR and mass spectra of compounds 4c and 4e are provided in the Supplementary Materials
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