Antimicrobial Activity and In silico ADME Prediction of Synthesised 8-hydroxyquinoline Azo Compounds against Some ESKAPE Human Pathogens and Mycobacterium smegmatis
Journal of Pharmaceutical Research International,
Page 68-80
DOI:
10.9734/jpri/2022/v34i42A36296
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
How to Cite
Amengor, C. D. K., Gyan, P., Danquah, C. A., Peprah, P., Harley, B. K., Orman, E., Ben, I. O., Tetteh, M., Adusei, E. B. A., Kekessie, F. K. and Okine, N. N. A. (2022) “Antimicrobial Activity and In silico ADME Prediction of Synthesised 8-hydroxyquinoline Azo Compounds against Some ESKAPE Human Pathogens and Mycobacterium smegmatis”, Journal of Pharmaceutical Research International, 34(42A), pp. 68-80. doi: 10.9734/jpri/2022/v34i42A36296.
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Available:https://doi.org/10.1155/2019/1250645
Desai NC, Bhatt N, Somani H, Trivedi A. () Synthesis, antimicrobial and cytotoxic activities of some novel thiazole clubbed 1,3,4-oxadiazoles. European Journal of Medicinal Chemistry. 2013;67:54–59.
Available:https://doi.org/10.1016/j.ejmech.2013.06.029
O’Donnell G, Poeschl R, Zimhony O, Gunaratnam M, Moreira JBC, Neidle S, Evangelopoulos D. Bioactive pyridine-N-oxide disulfides from allium stipitatum. Journal of Natural Products. vol. 2009;72:360–365.
Available:https://doi.org/10.1021/np800572r
Gibbons S. Plants as a source of bacterial resistance modulators and anti-infective agents. Phytochemistry Reviews. 2005; 4:63–78.
Available: https://doi.org/10.1007/s11101-005-2494-9
Cheng H, Xie Y, Villalobos LF, Song L, Peinemann KV, Nunes S, Hong PY. Antibiofilm effect enhanced by modification of 1,2,3-triazole and palladium nanoparticles on polysulfone membranes. Scientific Reports. 2016;6:1–12.
Available:https://doi.org/10.1038/srep24289
Shreve RN, Bennet BR. Studies in Azo Dyes. II. Preparation and Bacteriostatic Properties of Azo Derivatives of 8-Quinolinol, Journal of American Chemical Society. 1943;65:2243-2245.
Albasha M. Synthesis, Characterization of New Azo Compounds and Their Biological Evaluation. International Journal of Academic Scientific Research. 2018;4: 16-24.
Saylam A, Seferoğlu Z, Ertan N. Azo-8-hydroxyquinoline dyes: The synthesis, characterizations and 2 determination of tautomeric properties of some new 3 phenyl- and heteroarylazo-8-hydroxyquinolines. Journal of Molecular Liquids. 2014;195:267-276.
Available:http://dx.doi.org/10.1016/j.molliq.2014.02.02
Alavijeh MS, Palmer AM. The pivotal role of drug metabolism and pharmacokinetics in the discovery and development of new medicines. 2004;7:755–763.
PMID: 15334309
Araujo de Brito M. Pharmacokinetic study with computational tools in the medicinal chemistry course. Brazilian Journal of Pharmaceutical Sciences. 2011;4:795- 805
Whitty A, Zhong M, Viarengo L, Beglov D, Hall DR, Vajda S. Quantifying the chameleonic properties of macrocycles and other high-molecular-weight drugs. Drug Discovery Today. 2016;5:712-717.
Rajput A, Thakur A, Sharma S, Kumar M. ‘A biofilm: a resource of anti-biofilm agents and their potential implications in targeting antibiotic drug resistance,’ Nucleic acids Research. 2018;46:894–900.
Available:https://doi.org/10.1093/nar/gkx1157
DOI: 10.4137/PMC.S14459
Furuse Y. Analysis of research intensity on infectious disease by disease burden reveals which infectious diseases are neglected by researchers, PNAS Journal. 2019;116:478-483.
Available:https://doi.org/10.1073/pnas.1814484116
Coates AR, Halls G, Hu Y. Novel classes of antibiotics or more of the same? British Journal of Pharmacology. 2011;163:184–194.
Available:https://doi.org/10.1111/j.1476-5381.2011.01250.x
Wickremasinghe AR, Wickremasinghe R, Herath HDB, Fernando SD. Should chemoprophylaxis be a main strategy for preventing re-introduction of malaria in highly receptive areas? Sri Lanka a case in point. Malaria Journal. vol. 2017;16:1–6.
Available:https://doi.org/10.1186/s12936-017-1763-6
Soto SM. Role of efflux pumps in the antibiotic resistance of bacteria embedded in a biofilm, Virulence. 2013;4:223–229.
DOI: 10.4161/viru.23724
Lima AD, Chiaradia-delatorre LD, Mascarello A, Andrinéia K, Oliveira D, César P. Synthetic organic compounds with potential for bacterial biofilm inhibition, a path for the identification of compounds interfering with quorum sensing. International Journal of Antimicrobial Agents. 2013;42:519–523.
Available:https://doi.org/10.1016/j.ijantimicag.2013.07.006
Santajit S, Indrawattana N. Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens. BioMed Research International. 2016:1-8.
Available:https://doi.org/10.1155/2016/2475067
Manchanda V, Sinha S, Singh N. Multidrug resistant Acinetobacter. Journal of Global Infectious Diseases. 2010:291-304.
Available:https://doi.org/10.4103/0974-777x.68538.
Spampinato, C., Leonardi, D. Candida infections, causes, targets, and resistance mechanisms: Traditional and alternative antifungal agents. BioMed Research International. 2013:1-13.
Available:https://doi.org/10.1155/2013/204237.
Gordon SV, Parish T. Microbe profile: Mycobacterium tuberculosis: Humanity’s deadly microbial foe. Microbiology. vol. 2018;164:437– 439.
DOI: 10.1099/mic.0.000601
Palomino JC, Martin A. Drug resistance mechanisms in Mycobacterium tuberculosis. Antibiotics. 2014;3:317–340.
Available:https://doi.org/10.3390/antibiotics3030317
Haque S, Nawrot DA, Alakurtti S, Ghemtio L, Yli-kauhaluoma J. Screening and Characterisation of Antimicrobial Properties of Semisynthetic Betulin Derivatives. PLOS ONE. 2014;9, e102696.
DOI:10.1371/journal.pone.0102696.
Hyde J, Gorham C, Brackney DE, Steven B. Antibiotic resistant bacteria and commensal fungi are common and conserved in the mosquito microbiome. PLoS ONE. 2019;14(8):1–16.
Available:https://doi.org/10.1371/journal.pone.0218907
Hutchings M, Truman A, Wilkinson B. Antibiotics: past, present and future. Current Opinion in Microbiology. 2019; 51:72–80.
Available:https://doi.org/10.1016/j.mib.2019.10.008
Domalaon R, Idowu T, Zhanel GG, Schweizer F. Antibiotic hybrids: The next generation of agents and adjuvants against gram-negative pathogens? Clinical Microbiology Reviews. 2018;31:1–45.
Available:https://doi.org/10.1128/CMR.00077-17
Kyei SK, Akaranta O, Darko G. Synthesis, characterization and antimicrobial activity of peanut skin extract-azo-compounds. Scientific African. 2020;8:e00406
Available:https://doi.org/10.1016/j.sciaf.2020.e00406
Patel P, Patel PS. Synthesis, characterization, and antimicrobial activity of heterocyclic azo dye derivatives. World Scientific News. 2018;95:265–272.
Shihab NL, Intedhar KM. Synthesis of some novel heterocyclic azo dyes for acridine derivatives and evaluation of their antibacterial activities. Journal of Chemical and Pharmaceutical Research. 2013;5:345–354.
Stanasel O, Bota S. 2-Amino-1,3,4-thiadiazole as a potential scaffold for promising antimicrobial agents. Drug design, Development and Therapy. 2018; 12:1545–1566.
Available:https://doi.org/10.2147/DDDT.S155958.
Adu JK, Amengor CDK, Mohammed IN, Amaning-Danquah C, Owusu-Ansah C, Gbadago DD, Sarpong-Agyapong J. Synthesis and in vitro Antimicrobial and Anthelminthic Evaluation of Naphtholic and Phenolic Azo Dyes. Journal of Tropical Medicine. 2020:1-8.
Available:https://doi.org/10.1155/2020/4850492
Akram D, Elhaty IA. Synthesis and Antibacterial Activity of Rhodanine-Based Azo Dyes and their Use as Spectrophotometric Chemosensor for Fe 3 + Ions. Chemosensors. 2020;8:1-13.
Available:https://doi.org/10.3390/chemosensors8010016
Taboureau O, Baell JB, Fernández-Recio J, Villoutreix BO. Established and emerging trends in computational drug discovery in the structural genomics era. Chemistry and Biology. 2012;19:29–41.
Available:https://doi.org/10.1016/j.chembiol.2011.12.007
Sunil R, Pal S, Jayashree A. Molecular Hybridization - An Emanating Tool in Drug Design. Medicinal Chemistry. 2019;9:93–95.
DOI:10.2174/1568026619666190619115735.
Albasha M. Synthesis, Characterization of New Azo Compounds and Their Biological Evaluation. International Journal of Academic Scientific Research. 2018;4:16-24.
Dong J, Wang N, Yao Z. ADMETlab: a platform for systematic ADMET evaluation based on a comprehensively collected ADMET database. Journal of Cheminformatics. 2018;10:29.
Available: https://doi.org/10.1186/s13321-018-0283-x
Abdullahi M, Elijah S. In ‑ silico Molecular Docking and ADME / Pharmacokinetic Prediction Studies of Some Novel Carboxamide Derivatives as Anti ‑ tubercular Agents. Chemistry Africa; 2020.
Available: https://doi.org/10.1007/s42250-020-00162-3
Adusei EBA, Adosraku RK, Oppong-Kyekyeku J, Amengor CDK, Jibira Y. Resistance Modulation Action, Time-Kill Kinetics Assay, and Inhibition of Biofilm Formation Effects of Plumbagin from Plumbago zeylanica Linn. Journal of Tropical Medicine; 2019.
Available:https://doi.org/10.1155/2019/1250645
Desai NC, Bhatt N, Somani H, Trivedi A. () Synthesis, antimicrobial and cytotoxic activities of some novel thiazole clubbed 1,3,4-oxadiazoles. European Journal of Medicinal Chemistry. 2013;67:54–59.
Available:https://doi.org/10.1016/j.ejmech.2013.06.029
O’Donnell G, Poeschl R, Zimhony O, Gunaratnam M, Moreira JBC, Neidle S, Evangelopoulos D. Bioactive pyridine-N-oxide disulfides from allium stipitatum. Journal of Natural Products. vol. 2009;72:360–365.
Available:https://doi.org/10.1021/np800572r
Gibbons S. Plants as a source of bacterial resistance modulators and anti-infective agents. Phytochemistry Reviews. 2005; 4:63–78.
Available: https://doi.org/10.1007/s11101-005-2494-9
Cheng H, Xie Y, Villalobos LF, Song L, Peinemann KV, Nunes S, Hong PY. Antibiofilm effect enhanced by modification of 1,2,3-triazole and palladium nanoparticles on polysulfone membranes. Scientific Reports. 2016;6:1–12.
Available:https://doi.org/10.1038/srep24289
Shreve RN, Bennet BR. Studies in Azo Dyes. II. Preparation and Bacteriostatic Properties of Azo Derivatives of 8-Quinolinol, Journal of American Chemical Society. 1943;65:2243-2245.
Albasha M. Synthesis, Characterization of New Azo Compounds and Their Biological Evaluation. International Journal of Academic Scientific Research. 2018;4: 16-24.
Saylam A, Seferoğlu Z, Ertan N. Azo-8-hydroxyquinoline dyes: The synthesis, characterizations and 2 determination of tautomeric properties of some new 3 phenyl- and heteroarylazo-8-hydroxyquinolines. Journal of Molecular Liquids. 2014;195:267-276.
Available:http://dx.doi.org/10.1016/j.molliq.2014.02.02
Alavijeh MS, Palmer AM. The pivotal role of drug metabolism and pharmacokinetics in the discovery and development of new medicines. 2004;7:755–763.
PMID: 15334309
Araujo de Brito M. Pharmacokinetic study with computational tools in the medicinal chemistry course. Brazilian Journal of Pharmaceutical Sciences. 2011;4:795- 805
Whitty A, Zhong M, Viarengo L, Beglov D, Hall DR, Vajda S. Quantifying the chameleonic properties of macrocycles and other high-molecular-weight drugs. Drug Discovery Today. 2016;5:712-717.
Rajput A, Thakur A, Sharma S, Kumar M. ‘A biofilm: a resource of anti-biofilm agents and their potential implications in targeting antibiotic drug resistance,’ Nucleic acids Research. 2018;46:894–900.
Available:https://doi.org/10.1093/nar/gkx1157
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