Preparation, bacteriostatic, and in silico analysis of halogenated 4-methoxyphenyl-triazene derivatives

Davlye Noissy, Diosing and Ainaa Nadiah, Abd Halim and Nor Hisam, Zamakshshari and Zainab, Ngaini and Yeo, Kai Wei and Akshatha Handattu, Shankaranarayana and B. R. Prashantha, Kumar (2025) Preparation, bacteriostatic, and in silico analysis of halogenated 4-methoxyphenyl-triazene derivatives. Malaysian Journal of Analytical Sciences, 29 (2). pp. 1-14. ISSN 1934-2506

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Abstract

A series of diazoamino compounds, also known as triazene derivatives were successfully synthesised through the N-coupling diazotisation of p-anisidine with various halogenated substituted anilines at ortho, meta, and para positions. The series was obtained in low to moderate yields of 13-56%. Structural elucidation was performed via FTIR, 1H, and 13C NMR techniques. With ampicillin served as a positive control, the antibacterial efficacy of the synthesised compounds against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 via the Kirby-Bauer disk diffusion resulted in moderate to good inhibition measuring 6.6 ± 0.25 to 10.0 ± 0.00 mm, respectively. The minimum inhibitory concentration (MIC) values indicating inhibition of ≥ 8.8 mm yielded promising results, with MICs ranging from 82 to 121 ppm for E. coli and from 87 to 101 ppm for S. aureus. These values exceeded the standard ampicillin range of 96 to 127 ppm, suggesting potential for broader clinical applications. Molecular docking analysis of the compounds against CrtM and MurE protein receptors further supported these findings with binding scores of -7.48 to -8.27 kcal/mol and -7.26 to -7.94 kcal/mol, respectively. Notably, these scores surpassed those of ampicillin, which scored only -7.23 kcal/mol and -6.92 kcal/mol, respectively. This enhanced activity is believed to be attributed to the presence of hydrogen bonding and other hydrophobic interactions. Additionally, the bioavailability competencies of all compounds tested via ADMET analysis demonstrated compliance of each compound with Lipinski’s rule of five with zero violations.

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