Antimicrobial Activity and In silico ADME Prediction of Synthesised 8-hydroxyquinoline Azo Compounds against Some ESKAPE Human Pathogens and Mycobacterium smegmatis
Cedric D. K. Amengor *
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Health and Allied Sciences, Ho., Ghana.
Patrick Gyan
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Health and Allied Sciences, Ho., Ghana.
Cynthia Amaning Danquah
Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Paul Peprah
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Health and Allied Sciences, Ho., Ghana.
Benjamin K. Harley
Department of Pharmacognosy and Herbal Medicine, School of Pharmacy, University of Health and Allied Sciences, Ho., Ghana.
Emmanuel Orman
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Health and Allied Sciences, Ho., Ghana.
Inemisit O. Ben
Department of Pharmacology, School of Pharmacy, University of Health and Allied Sciences, Ho., Ghana.
Michael Tetteh
Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Emmanuel B. A. Adusei
Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Francis K. Kekessie
Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Nathaniel N. A. Okine
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Health and Allied Sciences, Ho., Ghana.
*Author to whom correspondence should be addressed.
Abstract
Introduction: Antimicrobial resistance has increasingly been a global health concern over the past decades and that has necessitated the quest to increase the pool of antibiotics.
Methods: Five (5) azo compounds were synthesised by diazotization and coupling procedures with yields of 60 – 92%. They were characterized by melting point determination, Ultra-Violet Visible, and Infra-red spectroscopy. High-throughput spot culture growth inhibition (HT-SPOTi) antimicrobial assay was used to evaluate the compounds. Computational studies was also employed to predict some pharmacokinetic properties of the azo compounds
Results: From the in silico studies, none of the compounds violated Lipinski’s rule and therefore, have the potential to be developed into an oral drug. They also showed Total Polar Surface Area (TPSA) values < 140 A2 (74.91 – 100.98 A2) and percentage absorption of 74 – 83 %. They were placed in category III of acute oral drugs. From the high-throughput spot culture growth inhibition antimicrobial assay, all the compounds possessed inhibitory activity against the ESKAPE human pathogens and Mycobacterium smegmatis, with MICs range of 3.9 \(\geq\) 500 \(\mu g/mL\). Except for 4e which showed liver toxicity, all the compounds demonstrated mutagenic and hepatotoxic tendencies. The modulatory assay of the azo compounds revealed that 4c and 4e modulated the antimicrobial activity of ciprofloxacin against Pseudomonas aeruginosa and Staphylococcus aureus. 4c and 4e also modulated the antimicrobial activity of rifampicin against Mycobacterium smegmatis. Exploiting the ability of 4c and 4e to act by a mode of action revealed that they have biofilm formation inhibitory potential.
Conclusion: Compounds 4c and 4e exhibited the best antimicrobial activity in terms of resistant modulation and biofilm inhibition against Pseudomonas aeruginosa, Staphylococcus aureus and Mycobacterium smegmatis.
Keywords: Azo compounds, antimicrobial, biofilm inhibition, resistance modulation, efflux pump