Copyright (c) 2024 Arun Kumar, Dr Govind Singh, Dr Rajiv Tonk
This work is licensed under a Creative Commons Attribution 4.0 International License.
In vitro Antibacterial, ADME and Toxicity Screening of Newly Synthesized 4-(Substituted phenyl)-2-(2-chloroquinolin-3-yl)thiazoles
Corresponding Author(s) : Arun Kumar
Asian Journal of Chemistry,
Vol. 36 No. 5 (2024): Vol 36 Issue 5, 2024
Abstract
A series of novel thiazole (Va-o) compounds were synthesized following multi-step synthetic process. Using analytical methods like nuclear magnetic resonance, mass spectrometry and FTIR, the elucidation of the structure of the synthesized compounds was performed. All the 15 novel thiazoles were assessed for their antibacterial activity. The synthesized thiazoles were examined for inhibitory antibacterial activity against a panel Gram-positive strain viz. Staphylococcus aureus (NCTC 65710), Streptococcus pyogenes (MTCC-442), Bacillus subtilis (NCIM 2250) and Gram-negative bacteria Pseudomonas aeruginosa (NCTC 10662) and Escherichia coli (NCTC 10418) by agar well diffusion technique. It was observed that some of the compounds, particularly those having substitution groups like chloro, fluoro and bromo in the phenyl ring bonded to thiazole nucleus, had moderate to good antibacterial activity. Quinoline clubbed thiazoles compounds Vk, Vl, Vn and Vo showed significant antibacterial against all bacterial strains having values of minimum inhibitory concentration (MIC) from 12.5 to 25 µg/mL. The results of antimicrobial investigation suggest that 2-chloroquinoline incorporated thiazole scaffold appears to more promising for developing potent antibacterial agents. Genome gyrase docking experiments (PDB ID: 1KZN) revealed a favourable binding relationship similar to that of the pre-occupied ligand clorobiocin. The study also provides in silico ADME and toxicity studies evaluation which revealed that compounds are impartially compatible and were devoid of potential toxicity except the hepatotoxicity.
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References
H. Carolus, K. Van Dyck and P. Van Dijck, Front. Microbiol., 10, 2162 (2019); https://doi.org/10.3389/fmicb.2019.02162
A. Zouhir, T. Jridi, A. Nefzi, J. Ben Hamida, Pharm. Biol., 54, 3136 (2016); https://doi.org/10.1080/13880209.2016.1190763
E.L. Berkow and S.R. Lockhart, Infect. Drug Resist., 10, 237 (2017); https://doi.org/10.2147/IDR.S118892
H.M.H.N. Bandara, D.L.A. Wood, I. Vanwonterghem, P. Hugenholtz, B.P.K. Cheung and L.P. Samaranayake, Sci. Rep., 10, 7769 (2020); https://doi.org/10.1038/s41598-020-64761-3
M. T. Chhabria, S. Patel, P. Modi and P. S. Brahmkshatriya, Curr. Top. Med. Chem., 16, 2841 (2016); https://doi.org/10.2174/1568026616666160506130731
S.H. Ali and A.R. Sayed, Synth. Commun., 51, 670 (2021); https://doi.org/10.1080/00397911.2020.1854787
A. Petrou, M. Fesatidou and A. Geronikaki, Molecules, 26, 3166 (2021); https://doi.org/10.3390/molecules26113166
M.F. Arshad, A. Alam, A.A. Alshammari, M.B. Alhazza, I.M. Alzimam, M.A. Alam, G. Mustafa, M.S. Ansari, A.M. Alotaibi, A.A. Alotaibi, S. Kumar, S.M.B. Asdaq, M. Imran, P.K. Deb, K.N. Venugopala and S. Jomah, Molecules, 27, 3994 (2022); https://doi.org/10.3390/molecules27133994
S. Kumar, S. Bawa, D. Kaushik and B.P. Panda, Arch. Pharm., 344, 474 (2011); https://doi.org/10.1002/ardp.201000352
S. Kumar, S. Bawa, S. Drabu and B.P. Panda, Med. Chem. Res., 20, 1340 (2011); https://doi.org/10.1007/s00044-010-9463-6
S. Kumar, N. Goel, O. Afzal, M.R. Ali and S. Bawa, J. Antibiot. Res., 1, 101 (2015); https://doi.org/10.15744/2574-5980.1.101
A.H. Kategaonkar, P.V. Shinde, A.H. Kategaonkar, S.K. Pasale, B.B. Shingate and M.S. Shingare, Eur. J. Med. Chem., 45, 3142 (2010); https://doi.org/10.1016/j.ejmech.2010.04.002
O. Meth-Cohn, B. Narine and B. Tarnowski, J. Chem. Soc., Perkin Trans. 1, 1520 (1981); https://doi.org/10.1039/p19810001520
C. Bagley, K. Chapaneri, C. Glover and E.A. Merritt, Synlett, 2615 (2004); https://doi.org/10.1055/s-2004-834812
A. Daina, O. Michielin and V. Zoete, Sci. Rep., 07, 42717 (2017); https://doi.org/10.1038/srep42717
P. Banerjee, A.O. Eckert, A.K. Schrey and R. Preissner, Nucleic Acids Res., 46(W1), W257 (2018); https://doi.org/10.1093/nar/gky318
A. Kashyap, D. Rani, S. Kumar and S. Bhatt, Int. J. Pharm. Sci. Drug Res., 15, 665 (2023); https://doi.org/10.25004/IJPSDR.2023.150515
R. Cruickshank, J.P. Duguid, B.P. Marion and R.H.A. Swain, Medical Microbiology, Churchill Livingstone: London, vol. II, edn. 12th (1975).