Copyright (c) 2025 S. Fuloria, L. Thangavelu, R. Murugan, R.J.S.A. Dass, B. Krishnamoorthy, F.J.M.D. Jackson, P. Venkatachalam, A. Rajendran, N.K. Fuloria

This work is licensed under a Creative Commons Attribution 4.0 International License.
Synthesis, Characterization, Molecular Docking, Cell viability and Biological Activity of New Metronidazole Analogues against Cellulitis Causing Pathogens
Corresponding Author(s) : S. Fuloria
Asian Journal of Chemistry,
Vol. 37 No. 5 (2025): Vol 37 Issue 5, 2025
Abstract
Development of microbial resistance against commercial imidazoles intended present study to develop some new metronidazole analogues against cellulitis causing pathogens. In present study, N-(4-substituted benzylidene)-2-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethoxy)-acetohydrazide (2a-c) were synthesized by treating hydrazide derivative of metronidazole (1) with various aromatic aldehydes. The structures of synthesized compounds 2a-c were characterized using FT-IR, 1H NMR, 13C NMR and mass spectrometric data. The synthesized compounds 2a-c were evaluated for their inhibitory potential against cellulitis triggering bacteria S. aureus, E. coli and cell viability profile using MTT assay. Among compounds 2a-c, compound 2c incorporated with high electronegative group, exhibited maximum inhibitory potential against cellulitis triggering pathogens. This potential was also supported by the docking data of compounds 2c against glucosamine-6-phosphate (2VF5). The significant antibacterial potential of compounds 2a-c against S. aureus and E. coli, high cell viability against HEK 293 cells (more than 75%) and high docking score of compounds with 2VF5 supports their potential application in cellulitis treatment. However, the synthesized compounds should be further evaluated for their in vivo preclinical significance.
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- Mallappa, M. Chahar, N. Choudhary, K.K. Yadav, M.T. Qasim, R. Zairov, A. Patel, V.K. Yadav and M. Jangir, J. Iran. Chem. Soc., 23, 1 (2024); https://doi.org/10.1007/s13738-024-03142-3
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- J.K. Nguyen, E. Hoxhallari and J. Daffy, Dermatol. Rep., 15, 9603 (2022); https://doi.org/10.4081/dr.2023.9603
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- E. Hejchman, H. Kruszewska, D. Maciejewska, B. Sowirka-Taciak, M. Tomczyk, A. Sztokfisz-Ignasiak, J. Jankowski and I. M³ynarczuk-Bia³y, Monatsh. Chem., 150, 255 (2019); https://doi.org/10.1007/s00706-018-2325-5
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- P. Ngamsurach and P. Praipipat, RSC Advances, 12, 26435 (2022); https://doi.org/10.1039/D2RA04611C
- N.P Yahaya and M.S. Mukhtar, Sci. J. Chem., 9, 9 (2021); https://doi.org/10.11648/j.sjc.20210901.12
- R. Kavitha, M.A. Sa'ad, S. Fuloria, N.K. Fuloria, M. Ravichandran and P. Lalitha, Antibiotics, 12, 306 (2023); https://doi.org/10.3390/antibiotics12020306
- A. Drefahl, J. Cheminform., 3, 1 (2011); https://doi.org/10.1186/1758-2946-3-1
- O. Trott and A.J. Olson, J. Comput. Chem., 31, 455 (2010); https://doi.org/10.1002/jcc.21334
- Hunter AD. ACD/ChemSketch 1.0 (freeware); ACD/ChemSketch 2.0 and its tautomers, dictionary, and 3D plug-ins; ACD/HNMR 2.0; ACD/CNMR 2.0.
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References
Mallappa, M. Chahar, N. Choudhary, K.K. Yadav, M.T. Qasim, R. Zairov, A. Patel, V.K. Yadav and M. Jangir, J. Iran. Chem. Soc., 23, 1 (2024); https://doi.org/10.1007/s13738-024-03142-3
S.K. Abbas, M.T. Jaafar, H.R. Ali and A.A. Alsarayreh, Mor. J. Chem., 12, 1222 (2024); https://doi.org/10.48317/IMIST.PRSM/morjchem-v12i3.48221
H.A. Al-Ghamdi, F.A. Almughem, M.A. Alshabibi, A.A. Bakr, A.A. Alshehri, A.H. Aodah, N.A. Al Zahrani, F.A. Tawfik and L.A. Damiati, Biomolecules, 14, 1198 (2024); https://doi.org/10.3390/biom14091198
I. Bayar and S. Akkoc, Russ. J. Org. Chem., 59, S7 (2023); https://doi.org/10.1134/S107042802313002X
R. Rrapi, S. Chand and D. Kroshinsky, Medical Clinics, 105, 723 (2021).
J.K. Nguyen, E. Hoxhallari and J. Daffy, Dermatol. Rep., 15, 9603 (2022); https://doi.org/10.4081/dr.2023.9603
E. Ortiz-Lazo, C. Arriagada-Egnen, C. Poehls and M. Concha-Rogazy, Actas Dermosifiliogr., 110, 124 (2019); https://doi.org/10.1016/j.ad.2018.07.010
E.H. Haindongo, D. Ndakolo, M. Hedimbi, O. Vainio, A. Hakanen and J. Vuopio, J. Glob. Antimicrob. Resist., 32, 35 (2023); https://doi.org/10.1016/j.jgar.2022.11.016
M. Lahyaoui, M. Filali, K. Benamar, R. Sghyar, K. Fikri-Benbrahim, A. Haoudi, A. Mazzah, S. El khattabi, E. Mestafa El Hadrami, Y. Kandri Rodi and N. Kheira Sebbar, Results Chem., 10, 101699 (2024); https://doi.org/10.1016/j.rechem.2024.101699
D. Leitsch, Parasitology, 146, 1167 (2019); https://doi.org/10.1017/S0031182017002025
S.J. Hamid and T. Salih, Drug Des. Devel. Ther., 16, 2275 (2022); https://doi.org/10.2147/DDDT.S364746
E. Hejchman, H. Kruszewska, D. Maciejewska, B. Sowirka-Taciak, M. Tomczyk, A. Sztokfisz-Ignasiak, J. Jankowski and I. M³ynarczuk-Bia³y, Monatsh. Chem., 150, 255 (2019); https://doi.org/10.1007/s00706-018-2325-5
V. Sharma, M. Yadav, A. Bhatia, S. Muthaiah and J.K. Kapoor, J. Mol. Struct., 1297, 136924 (2024); https://doi.org/10.1016/j.molstruc.2023.136924
P.M. Thakor, J.D. Patel, R.J. Patel, S.H. Chaki, A.J. Khimani, Y.H. Vaidya, A.P. Chauhan, A.B. Dholakia, V.C. Patel, A.J. Patel, N.H. Bhavsar and H.V. Patel, ACS Omega, 9, 35431 (2024); https://doi.org/10.1021/acsomega.4c02007
P. Ngamsurach and P. Praipipat, RSC Advances, 12, 26435 (2022); https://doi.org/10.1039/D2RA04611C
N.P Yahaya and M.S. Mukhtar, Sci. J. Chem., 9, 9 (2021); https://doi.org/10.11648/j.sjc.20210901.12
R. Kavitha, M.A. Sa'ad, S. Fuloria, N.K. Fuloria, M. Ravichandran and P. Lalitha, Antibiotics, 12, 306 (2023); https://doi.org/10.3390/antibiotics12020306
A. Drefahl, J. Cheminform., 3, 1 (2011); https://doi.org/10.1186/1758-2946-3-1
O. Trott and A.J. Olson, J. Comput. Chem., 31, 455 (2010); https://doi.org/10.1002/jcc.21334
Hunter AD. ACD/ChemSketch 1.0 (freeware); ACD/ChemSketch 2.0 and its tautomers, dictionary, and 3D plug-ins; ACD/HNMR 2.0; ACD/CNMR 2.0.
S.A. Matar, W.H. Talib, M.S. Mustafa, M.S. Mubarak and M.A. AlDamen, Arab. J. Chem., 8, 850 (2015); https://doi.org/10.1016/j.arabjc.2012.12.039