Synthesis of 5-heptadecyl-4H-1,2,4-triazole incorporated indole moiety: Antiviral (SARS-CoV-2), antimicrobial, and molecular docking studies

• Published in: Journal of molecular structure Vol. 1303; p. 137517
• Main Authors: Salam, Hayam A．Abd El, Abo-Salem, Heba M., Kutkat, Omnia, Abdel-Aziz, Mohamed S., Montaser, Ahmed Saad, El-Sawy, Eslam Reda
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05.05.2024
• Subjects: Antimicrobial; Indole-3-carboxaldehyde; Mannich base; Molecular docking study; SAR-CoV-2; Schiff base; Stearic acid; Schiff base; Antimicrobial; Molecular docking study; MBCS; Indole-3-carboxaldehyde; Stearic acid; Mannich base; BIS; SAR-CoV-2
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2024.137517

•Compounds formula, (E)−5-heptadecyl-4-(((1-benzyl-1H-indol-3-yl) methylene) amino)−4H-1,2,4-triazole-3-S-alkyl, where the alkyl group is ethan-1-ol (6d) or propane-1,2-diol)7d(showed antiviral activity against NRC-03-nhCoV with IC50 of 8.7 and 8.925 μM, respectively.•(E)−5-heptadecyl-4-(((1-methyl-1H-indol-3-yl)methylene)amino)−4H-1,2,4-triazole −3-thiol (5b) showed excellent MIC values against all test microbes with values of 19.53, 39.06, and 39.125 µg/mL against S. aureus, E. coli, and C. albicans, respectively.•Compound 5b exhibited release of reducing sugars and proteins with variable values on test microbes, which confirmed the effect of 5b on the bacterial cell well (biosynthesis of cell well peptidoglycan).•Compound 5b was confirmed to be able to disrupt outer and inner membranes and interact with membrane protein and intracellular targets by scanning electron microscopic study (SEM).•A molecular docking study of the potent compounds against the key viral and microbial protein targets has highlighted the antiviral and antimicrobial behavior of these compounds. Two series of Schiff bases and Mannich bases derived from 5-heptadecyl-4H-1,2,4-triazole hybrids of indole moiety have been synthesized. First, the acid-catalyzed reaction of N-substituted-1H-indole-3-carboxaldehydes with the modified fatty acid, 4-amino-5-heptadecyl-4H-1,2,4-triazole-3-thiol, afforded 1,2,4-triazole Schiff bases 5a-d. Treatment of 5a-d with some halo-compounds gave S-alkyl-1,2,4-triazoles 6a-d to 9a-d. Additionally, the reaction of 5a-d with different secondary amine and paraformaldehyde afforded Mannich base products 10a-d to 13a-d. Basically, viral infections are often followed by bacterial infections that require antimicrobial treatment. The antiviral bioassay revealed that compounds 6d and 7d exhibited significant antiviral activity against NRC-03-nhCoV with IC50 equal 8.7 and 8.925 μM, respectively. Next, the synthesized compounds were evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacteria as well as yeast and fungi. Compound 5b exhibited effective antimicrobial activities against all microbial test strains. 5b revealed MIC values of 19.53 μg/mL against S. aureus, 39.063 μg/mL against E. coli, and 39.125 μg/mL against C. albicans. On top of that, the release of reducing sugars and proteins from the treated bacterial strains over the untreated bacterial strains was undertaken to describe the effect of compound 5b on the intact cells. Furthermore, scanning electron microscopy (SEM) has been applied to study the possible sterilization process of the antimicrobial compound 5b. The results indicated the possibility of destroying the cell membrane structure of microbes, resulting in incomplete microbial structures, and thus achieving inhibition. To putatively highlight the antiviral and antimicrobial activities of the potent compounds, they were subjected to molecular docking against the key viral and microbial protein targets.