Synthesis of halogenated azo-aspirin analogues from natural product derivatives as the potential antibacterial agents

Abstract

Chemical modification of medicines from natural product-based molecules has become of interest in recent years. In this study, a series of halogenated azo derivatives 1a-d were synthesised via coupling reaction, followed by Steglich esterification with aspirin (a natural product derivative) to form azo derivatives 2a-d. While, halogenated azo-aspirin 3a-d were synthesised via direct coupling reaction of aspirin and diazonium salt. Bacteriostatic activity was demonstrated against E. coli and S. aureus via turbidimetric kinetic method. Compound 3a-d showed excellent antibacterial activities against E. coli (MIC 75–94 ppm) and S. aureus (MIC 64–89 ppm) compared to ampicillin (MIC 93 and 124 ppm respectively), followed by 1a-d and 2a-d. The presence of reactive groups of –OH, N=N, C=O and halogens significantly contribute excellent interaction towards E. coli and S. aureus. Molecular dockings analysis of 3a against MIaC protein showed binding free energy of −7.2 kcal/mol (E. coli) and −6.6 kcal/mol (S. aureus).

Keywords:

• Aspirin
• azo
• turbidimetric
• chemical modification
• antibacterial

Acknowledgements

The authors acknowledge Universiti Malaysia Sarawak and Malaysia Ministry of Science, Technology and Innovation for the financial support through FRGS/ST01(02)/968/2013(09) and FRGS/ST01(01)/1298/2015(15).