Malays. J. Anal. Sci. Volume 29 Number 2 (2025): 1312

Research article

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

Davlye Noissy Diosing¹, Ainaa Nadiah Abd Halim^*1, Nor Hisam Zamakshshari¹, Zainab Ngaini¹, Yeo Kai Wei¹, Akshatha Handattu Shankaranarayana², and B. R. Prashantha Kumar²

¹Faculty of Resource Science and Technology, Universiti Malaysia Sarawak,94300 Kota Samarahan, Sarawak, Malaysia

²Department of Pharmaceutical Chemistry, JSS College of Pharmacy, Sri Shivarathreeshwara Nagar, Mysuru- 570015, India

^*Corresponding author: ahanadiah@unimas.my

Received: 13 September 2024; Revised: 10 December 2024; Accepted: 3 December 2025; Published: 27 March 2025

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.

Keywords: diazoamino, antibacterial activities, ADMET, N-coupling, in silico

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