Synthesis, DFT investigations, antioxidant, antibacterial activity and SAR-study of novel thiophene-2-carboxamide derivatives

• Published in: BMC chemistry 2023-02, Vol.17 (1), p.6-6, Article 6
• Main Authors: Metwally, Heba M., Khalaf, Norhan A., Abdel-Latif, Ehab, Ismail, Mohamed A.
• Format: Article
• Language: English
• Subjects: 2-Chloroacetamide; Acrylamide; Amino acids; Ampicillin; Antibacterial agents; Antioxidant; Antioxidants; Ascorbic acid; Chemical synthesis; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Coliforms; Density functional theory; Density functionals; DFT calculations; E coli; Electronic properties; Energy gap; Escherichia coli; Gram-positive bacteria; Investigations; Molecular docking; Molecular orbitals; NMR; Nuclear magnetic resonance; Protein binding; Proteins; Pseudomonas aeruginosa; Thiophene; Thiophene-2-carboxamide
• ISSN: 2661-801X; 2661-801X
• DOI: 10.1186/s13065-023-00917-2

Synthetic strategy for the synthesis of thiophene 2-carboxamide derivatives substituted with hydroxyl, methyl and amino groups at position-3 was proposed. The strategy includes the cyclization of the precursor ethyl 2-arylazo-3-mercapto-3-(phenylamino)acrylate derivatives, 2-acetyl-2-arylazo-thioacetanilide derivatives and N -aryl-2-cyano-3-mercapto-3-(phenylamino)acrylamide derivatives with N -(4-acetylphenyl)-2-chloroacetamide in alcoholic sodium ethoxide. IR, 1 H NMR, and mass spectroscopic analyses were used to characterize the synthesized derivatives. In addition, molecular, electronic properties of the synthesized products were studied by the density functional theory (DFT) where they exhibited close HOMO–LUMO energy gap (ΔE H-L ) in which the amino derivatives 7a-c have the highest while the methyl derivatives 5a-c were the lowest. Using the ABTS method, the antioxidant properties of the produced compounds were evaluated, where amino thiophene-2-carboxamide 7a exhibit significant inhibition activity 62.0% compared to ascorbic acid The antibacterial activity against two pathogenic Gram-positive bacteria ( Staphylococcus aureus and Bacillus subtilis ) and two of pathogenic Gram-negative bacteria ( Escherichia coli and Pseudomonas aeruginosa ) revealed that 7b records the highest activity index compared to ampicillin 83.3, 82.6, 64.0, 86.9%, respectively. Furthermore, the thiophene-2-carboxamide derivatives were docked with five different proteins with the use molecular docking tools and the results explained interactions between amino acid residue of enzyme and compounds. Compounds 3b and 3c showed the highest binding score with 2AS1 protein. Graphical Abstract