Spectral Investigations, DFT Studies, ADME Analysis, Molecular Docking of New Piperidine Derivatives with Potential Antimicrobial Activity

Khushbu Agrawal; Tarun Patel; Shavi Thakur; Kruti Patel; Sumit Mittal

doi:10.17485/IJST/v16i35.389

Article

Spectral Investigations, DFT Studies, ADME Analysis, Molecular Docking of New Piperidine Derivatives with Potential Antimicrobial Activity

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Indian Journal of Science and Technology

DOI: 10.17485/IJST/v16i35.389

Year: 2023, Volume: 16, Issue: 35, Pages: 2835-2844

Original Article

Spectral Investigations, DFT Studies, ADME Analysis, Molecular Docking of New Piperidine Derivatives with Potential Antimicrobial Activity

Khushbu Agrawal^1*, Tarun Patel², Shavi Thakur¹, Kruti Patel¹, Sumit Mittal³

¹Department of Chemistry, Shree Maneklal M. Patel Institute of Sciences and Research, Sector 15/23, Kadi Sarva Vishwavidyalaya, Gandhinagar, 382023, Gujarat, India
²Department of Chemistry, Sir P T Science College, HNGU, Modasa
³School of Advanced Sciences and Languages (SASL), VIT Bhopal University, Kothri Kalan, Near Indore Road, Bhopal, 466114, Madhya Pradesh, India

*Corresponding Author
Email: [email protected]

Received Date:21 February 2023, Accepted Date:08 August 2023, Published Date:19 September 2023

This work is licensed under a Creative Commons Attribution 4.0 International License.

Abstract

Objective: To explore the possibility of obtaining effective and harmless antibacterial drugs by conventional synthesis of new piperidine analogs. Methods: The target compound was carried out by cyclization reaction involving aromatic aldehydes and amine and further evaluated for their antimicrobiological assay using agar disc diffusion method. Computational investigation such as density functional theory (DFT) was carried out by B3LYP/6-31G (d,p) method to evaluate their electronic characteristics. Absorption, Distribution, Metabolism, and Excretion (ADME) properties were evaluated using the Swiss ADME server. The Antimicrobial activity was investigated using molecular docking and that molecule was prepared using MGL Tools 1.5.7. Auto Dock Vina 1.2.0. Findings: Among all the synthesized compounds 5a to 5h, compounds 5b and 5e showed good anti-bacterial properties against three pathogenic bacterial strains. B. subtilis is inhibited by compound 5b at a concentration of 26 mm. B. subtilis is inhibited by compound 5e at a concentration of 25 mm. Molecular Docking revealed that molecules 5b and 5e consistently showed a large binding affinity for all six target proteins, which was similar to that of the reference molecule, streptomycin. Drug-likeness predictions and the ADME analysis showed that most of the molecules do not violate any of the five Lipinski rule while some have only one or two violations, primarily because of high molecular weight. Novelty: In order to investigate the anti-bacterial impact of piperidine derivatives, a lot of work has been put into their synthesis and evaluation. These results might influence the creation and advancement of anti-microbial medication candidates that are more potent.

Keywords: Piperidine; Antimicrobial; SAR Study; Molecular Docking; ADME Study; DFT

References

Rishikesan R, Karuvalam RP, Muthipeedika NJ, Sajith AM, Eeda KR, Pakkath R, et al. Synthesis of some novel piperidine fused 5-thioxo-1H-1,2,4-triazoles as potential antimicrobial and antitubercular agents. Journal of Chemical Sciences. 2021;133(1). Available from: https://doi.org/10.1007/s12039-020-01872-4
Zabiulla AO, FH, Am S, Al-Ghorbani M, Khanum SA. Recent investigation on heterocycles with one nitrogen [piperidine, pyridine and quinoline. Journal of the Iranian Chemical Society. 2022;19(1):23–27. Available from: https://doi.org/10.1007/s13738-021-02293-x
Ramalingam A, Mustafa N, Chng WJ, Medimagh M, Sambandam S, Issaoui N. 3-Chloro-3-methyl-2,6-diarylpiperidin-4-ones as Anti-Cancer Agents: Synthesis, Biological Evaluation, Molecular Docking, and In Silico ADMET Prediction. Biomolecules. 2022;12(8):1093. Available from: https://doi.org/10.3390/biom12081093
Saadon KE, Taha NMH, Mahmoud NA, Elhagali GAM, Ragab A. Synthesis, characterization, and in vitro antibacterial activity of some new pyridinone and pyrazole derivatives with some in silico ADME and molecular modeling study. Journal of the Iranian Chemical Society. 2022;19(9):3899–3917. Available from: https://doi.org/10.1007/s13738-022-02575-y
Zala AR, Rajani DP, Kumari P. Design, synthesis, molecular docking and in silico ADMET investigations of novel piperidine-bearing cinnamic acid hybrids as potent antimicrobial agents. Journal of the Iranian Chemical Society. 2023;20(8):1843–1856. Available from: https://doi.org/10.1007/s13738-023-02801-1
Chen QS, Li JQ, Zhang QW. Application of Chiral Piperidine Scaffolds in Drug Design. Pharmaceutical Fronts. 2023;05(01):e1–e14. Available from: https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0043-1764218.pdf
Yıldız M, Yıldırım H, Bayrak N, Çakmak SM, Mataracı-Kara E, Özbek-Çelik B, et al. Design, synthesis, in vitro and in silico characterization of plastoquinone analogs containing piperidine moiety as antimicrobial agents. Journal of Molecular Structure. 2023;1277:134845. Available from: https://doi.org/10.1016/j.molstruc.2022.134845
Mekky AEM, Taha NAS, Mohammed NG, Hussein FRM, Abdelfattah EH, Eldin AAG, et al. Development of pyrazolo[1,5 a]pyrimidine-based antibacterial agents. Synthetic Communications. 2023;53(13):1053–1068. Available from: https://doi.org/10.1080/00397911.2023.2209815
Hussein AA, Slaihim MM. Synthesis, And Characterization of Some New Schiff Bases Derivatives for Piperidine, 3-Amino-1,2,4-Tri azole-5 -Thiolate Salt and Biological Evaluation as Antibacterial Agents. Journal of Population Therapeutics and Clinical Pharmacology. 2022;29(2):193–202. Available from: https://doi.org/10.47750/jptcp.2022.971
Nikonov G, Bobrov S. Comprehensive Heterocyclic Chemistry III.
Marinescu M. Synthesis of Antimicrobial Benzimidazole–Pyrazole Compounds and Their Biological Activities. Antibiotics. 2021;10(8):1002. Available from: https://doi.org/10.3390/antibiotics10081002
Shaikh TM, Debebe H. Synthesis and Evaluation of Antimicrobial Activities of Novel N-Substituted Indole Derivatives. Journal of Chemistry. 2020;2020:1–9. Available from: https://doi.org/10.1155/2020/4358453
Boyanova L, Gergova G, Nikolov R, Derejian S, Lazarova E, Katsarov N, et al. Activity of Bulgarian propolis against 94 Helicobacter pylori strains in vitro by agar-well diffusion, agar dilution and disc diffusion methods. Journal of Medical Microbiology. 2005;54(5):481–483. Available from: https://doi.org/10.1099/jmm.0.45880-0
Dan Z, Rain N, Badrul A, Adlin AR, Norazah A, A. In vitro screening of five local medicinal plants for antibacterial activity using disc diffusion method. Tropical Biomedicine. 22(2):165–170. Available from: https://www.msptm.org/files/165_-_170_In_vitro_screening.pdf
Nielsen AB, Holder A. 2009.
Frisch MJ, Trucks GW, Schlegel HS, Scuseria GE, Robb MA, Cheeseman JR, et al. Wallingford CT. 2013.
Zong Y, Bice TW, Ton-That H, Schneewind O, Narayana SVL. Crystal Structures of Staphylococcus aureus Sortase A and Its Substrate Complex. Journal of Biological Chemistry. 2004;279(30):31383–31389. Available from: https://doi.org/10.1074/jbc.M401374200
Heaslet H, Harris M, Fahnoe K, Sarver R, Putz H, Chang J, et al. Structural comparison of chromosomal and exogenous dihydrofolate reductase from<i>Staphylococcus aureus</i>in complex with the potent inhibitor trimethoprim. Proteins: Structure, Function, and Bioinformatics. 2009;76(3):706–717. Available from: https://doi.org/10.1002/prot.22383
Zhu W, Zhang Y, Sinko W, Hensler ME, Olson J, Molohon KJ, et al. Antibacterial drug leads targeting isoprenoid biosynthesis. Proceedings of the National Academy of Sciences. 2013;110(1):123–128. Available from: https://doi.org/10.1073/pnas.1219899110
Narramore S, Stevenson CEM, Maxwell A, Lawson DM, Fishwick CWG. New insights into the binding mode of pyridine-3-carboxamide inhibitors of E. coli DNA gyrase. Bioorganic & medicinal chemistry. 2019;27:3546–3550. Available from: https://doi.org/10.1016/j.bmc.2019.06.01i
Sanner MF. Python: A Programming Language for Software Integration and Development. Journal of Molecular Graphics and Modelling. 1999;17(1):5–7. Available from: https://pubmed.ncbi.nlm.nih.gov/10660911/
Eberhardt J, Santos-Martins D, Tillack AF, Forli S. AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings. Journal of Chemical Information and Modeling. 2021;61(8):3891–3898. Available from: https://doi.org/10.1021/acs.jcim.1c00203
Laskowski RA, Swindells MB. LigPlot+: multiple ligand-protein interaction diagrams for drug discovery. Journal of Chemical Information and Modeling. 2011;5(10):1. Available from: https://doi.org/10.1021/ci200227u
Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports. 2017;7(1). Available from: https://doi.org/10.1038/srep42717

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© 2023 Agrawal et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Published By Indian Society for Education and Environment (iSee)