Unfolding the Antibacterial Activity and Acetylcholinesterase Inhibition Potential of Benzofuran-Triazole Hybrids: Synthesis, Antibacterial, Acetylcholinesterase Inhibition, and Molecular Docking Studies

Abstract

In this study, a series of novel benzofuran-based 1,2,4-triazole derivatives (10a–e) were synthesized and evaluated for their inhibitory potential against acetylcholinesterase (AChE) and bacterial strains (E. coli and B. subtilis). Preliminary results revealed that almost all assayed compounds displayed promising efficacy against AChE, while compound 10d was found to be a highly potent inhibitor of AChE. Similarly, these 5-bromobenzofuran-triazoles 10a–e were screened against B. subtilis QB-928 and E. coli AB-274 to evaluate their antibacterial potential in comparison to the standard antibacterial drug penicillin. Compound 10b was found to be the most active among all screened scaffolds, with an MIC value of 1.25 ± 0.60 µg/mL against B. subtilis, having comparable therapeutic efficacy to the standard drug penicillin (1 ± 1.50 µg/mL). Compound 10a displayed excellent antibacterial therapeutic efficacy against the E. coli strain with comparable MIC of 1.80 ± 0.25 µg/mL to that of the commercial drug penicillin (2.4 ± 1.00 µg/mL). Both the benzofuran-triazole molecules 10a and 10b showed a larger zone of inhibition. Moreover, IFD simulation highlighted compound 10d as a novel lead anticholinesterase scaffold conforming to block entrance, limiting the swinging gate, and disrupting the catalytic triad of AChE, and further supported its significant AChE inhibition with an IC50 value of 0.55 ± 1.00 µM. Therefore, compound 10d might be a promising candidate for further development in Alzheimer’s disease treatment, and compounds 10a and 10b may be lead antibacterial agents.

Synthesis, Cytotoxic, and Computational Screening of Some Novel Indole–1,2,4-Triazole-Based S-Alkylated N-Aryl Acetamides

“…The resultant intermediate 5 was added to a KOH (0.08 g, 1.58 mmol) solution in water (5 mL) and allowed to reflux for 4 h. After cooling, diluted HCl was added to the solution to make it acidic, and the formed precipitate was filtered out. Recrystallization of precipitate from ethanol provided the title triazole-3-thione 6 as a white solid [39,40], as depicted in Scheme 1.…”

“…Subsequently, hy-drazinolysis of ester 2 with hydrazine hydrate in ethanol afforded the 2-(1H-indol-3-yl)acetohydrazide 3 in a 96% yield [38]. The 2-(1H-indol-3-yl)acetohydrazide 3 upon treatment with 3,4-dichlorophenyl isothiocyanate 4 yielded intermediate 5, which under reflux in KOH furnished the desired indole-linked 1,2,4-triazole-3-thione 6 in a 75% yield [39,40]. Finally, the alkylation of the resultant 1,2,4-triazole-3-thione 6 with various 2-bromo-N-arylacetamides 7a-f in DCM and pyridine at room temperature accomplished the target products 8a-f in a 69-82% yield (Scheme 1) [41].…”

A Comprehensive Review on Benzofuran Synthesis Featuring Innovative and Catalytic Strategies

“…Benzofuran derivatives have been found to be active against bacterial, − viral, , inflammatory, and protozoal diseases . For example, diabetes, HIV, tuberculosis, epilepsy, and Alzheimer’s disease are some of the most common and widely occurring diseases, against which benzofuran derivatives have been known to play a therapeutic role.…”