Exploring the antibacterial potential of novel fenamate-based derivatives: insights from molecular docking studies
DOI:
https://doi.org/10.60988/p.v37i2S.224Keywords:
antibacterial; fenamate; antimicrobial resistance; fatty acids; dockingAbstract
The rapid emergence of antibiotic-resistant bacteria poses a critical global health threat, highlighting the urgent need for novel antimicrobial agents. In this context, fenamate-based drugs (nonsteroidal anti-inflammatory compounds containing a fenamic acid scaffold) have recently gained attention as promising antibacterial candidates. These agents have demonstrated potent activity against a spectrum of pathogenic bacteria, including multidrug-resistant (MDR) strains. In the present study, several newly synthesized derivatives incorporating a fenamate moiety were evaluated for their antibacterial properties against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli and Pseudomonas aeruginosa by using the agar diffusion technique. Most of the fenamate derivatives exhibited notable antibacterial activity, particularly against E. coli. Compounds 1, 3, and 5 showed the highest inhibitory effects, with compound 3 demonstrating the most potent activity, effectively suppressing all tested bacterial strains at concentrations as low as 250 µg/mL. These findings underscore the therapeutic potential of fenamate-based compounds in combating antibiotic resistance. Their capacity to overcome MDR mechanisms, possible synergistic interactions with existing antibiotics, and additional immunomodulatory properties render them compelling candidates for further investigation as next-generation antimicrobial therapies.
References
1. Årdal C., Balasegaram M., Laxminarayan R., McAdams D., Outterson K., Rex J.H., et al. Antibiotic development - economic, regulatory and societal challenges. Nat. Rev. Microbiol. 18(5), 267–274, 2020. DOI: 10.1038/s41579-019-0293-3
2. Simpkin V.L., Renwick M.J., Kelly R., Mossialos E. Incentivising innovation in antibiotic drug discovery and development: progress, challenges and next steps. J. Antibiot. (Tokyo) 70(12), 1087–1096, 2017. DOI: 10.1038/ja.2017.124
3. Laxminarayan R., Duse A., Wattal C., Zaidi A.K., Wertheim H.F., Sumpradit N., et al. Antibiotic resistance – the need for global solutions. Lancet Infect. Dis. 13(12), 1057–1598, 2013. DOI: 10.1016/S1473-3099(13)70318-9
4. Wang Y.T., Shi T.Q., Fu J., Zhu H.L. Discovery of novel bacterial FabH inhibitors (pyrazol-benzimidazole amide derivatives): design, synthesis, bioassay, molecular docking and crystal structure determination. Eur. J. Med. Chem. 171, 209–220, 2019. DOI: 10.1016/j.ejmech.2019.03.026
5. Zhang Y.M., Rock C.O. Fatty acid and phospholipid biosynthesis in prokaryotes. In: Ridgway N.D., McLeod R.S. (eds). Biochemistry of Lipids, Lipoproteins and Membranes. Sixth Edition. Amsterdam: Elsevier, 73–112, 2016. DOI: 10.1016/B978-0-444-63438-2.00003-1
6. Ahmed S., Sheraz M.A., Ahmad I. Tolfenamic acid. Profiles Drug Subst. Excip. Relat. Methodol. 43, 255–319, 2018. DOI: 10.1016/bs.podrm.2018.01.001
7. Seong Y.J., Alhashimi M., Mayhoub A., Mohammad H., Seleem M.N. Repurposing fenamic acid drugs to combat multidrug-resistant Neisseria gonorrhoeae. Antimicrob. Agents Chemother. 64(7), e02206–e02219, 2020. DOI: 10.1128/AAC.02206-19
8. Mehihi A.A.R., Kubba A.A.R., Shihab W.A., Tahtamouni L.H. New tolfenamic acid derivatives with hydrazine-1-carbothioamide and 1,3,4-oxadiazole moieties targeting VEGFR: synthesis, in silico studies, and in vitro anticancer assessment. Med. Chem. Res. 32, 2334–2348, 2023. DOI: 10.1007/s00044-023-03137-4
9. Li J., Fu A., Zhang L. An overview of scoring functions used for protein-ligand interactions in molecular docking. Interdiscip. Sci. 11(2), 320–328, 2019. DOI: 10.1007/s12539-019-00327-w