Login Register Cart 0
Generic placeholder image

Current Organic Chemistry

Editor-in-Chief

ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Synthesis and Evaluation of Antimicrobial Activity of N-Substituted Indole Derivatives and Molecular Docking Studies

Author(s): Ashish Ranjan Dwivedi, Vijay Kumar, Neha, Kailash Jangid, Bharti Devi, Mahesh Kulharia, Rakesh Kumar and Vinod Kumar*

Volume 26, Issue 16, 2022

Published on: 13 December, 2022

Page: [1565 - 1574] Pages: 10

DOI: 10.2174/1385272827666221117140650

Price: $65

Abstract

The increasing burden of microbial infection and emerging resistance against the available antimicrobial drugs drives the development of new agents. Two different series of indole-based compounds (VN-1 to VN-18) were synthesized and analyzed for antimicrobial activity by calculating the diameter of the inhibition zone using the broth dilution method and well diffusion method against Escherichia coli (E. coli) and environmental microbes. Most of the compounds displayed good to moderate activity against E. coli, and VN-4 and VN-9 displayed good inhibitory activity against the tested microbes. Molecular docking and binding energy calculation studies of all the synthesized compounds have been performed for targeting FabI, where most of the compounds showed significant interactions with the aromatic nicotinamide moiety of NAD+. In molecular dynamics studies, VN-9 stays inside the binding cavity for sufficient time to induce antimicrobial activity. Thus, these indole-based derivatives may lead to the development of new antimicrobial agents that may act as FabI inhibitors.

Keywords: Indole synthesis, arylation, antimicrobial activity, molecular docking studies, molecular dynamics studies, physicochemical properties.

« Previous Next »
Graphical Abstract

[1]
Sharma, V.; Katyal, S.; Farooque, K.; Mathur, P.; Malhotra, R. Antimicrobial susceptibility pattern of pus culture of surgical site infections in Trauma Centre. Int. J. Infect. Dis., 2020, 101, 74-75.
[http://dx.doi.org/10.1016/j.ijid.2020.09.223]
[2]
Mohiuddin, A.K. Pharmacist-Led Antimicrobial Stewardship. Am. J. Pharmacol., 2019, 2, 1015.
[3]
Cano, A.; Ettcheto, M.; Espina, M.; López-Machado, A.; Cajal, Y.; Rabanal, F.; Sánchez-López, E.; Camins, A.; García, M.L.; Souto, E.B. State-of-the-art polymeric nanoparticles as promising therapeutic tools against human bacterial infections. J. Nanobiotechnology, 2020, 18(1), 156.
[http://dx.doi.org/10.1186/s12951-020-00714-2] [PMID: 33129333]
[4]
Dixit, A.; Kumar, N.; Kumar, S.; Trigun, V. Antimicrobial resistance: Progress in the decade since emergence of New Delhi Metallo-β-Lactamase in India. Indian J. Community Med., 2019, 44(1), 4-8.
[PMID: 30983704]
[5]
Tagliabue, A.; Rappuoli, R. Changing priorities in vaccinology: Antibiotic resistance moving to the top. Front. Immunol., 2018, 9, 1068.
[http://dx.doi.org/10.3389/fimmu.2018.01068] [PMID: 29910799]
[6]
Schillaci, D.; Spanò, V.; Parrino, B.; Carbone, A.; Montalbano, A.; Barraja, P.; Diana, P.; Cirrincione, G.; Cascioferro, S. Pharmaceutical approaches to target antibiotic resistance mechanisms. J. Med. Chem., 2017, 60(20), 8268-8297.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00215] [PMID: 28594170]
[7]
Alpert, P.T. Superbugs: Antibiotic resistance is becoming a major public health concern. Home Health Care Manage. Pract., 2017, 29(2), 130-133.
[http://dx.doi.org/10.1177/1084822316659285]
[8]
Picconi, P.; Hind, C.K.; Nahar, K.S.; Jamshidi, S.; Di Maggio, L.; Saeed, N.; Evans, B.; Solomons, J.; Wand, M.E.; Sutton, J.M.; Rahman, K.M. New broad-spectrum antibiotics containing a pyrrolobenzodiazepine ring with activity against multidrug-resistant gram-negative bacteria. J. Med. Chem., 2020, 63(13), 6941-6958.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00328] [PMID: 32515951]
[9]
Breijyeh, Z.; Jubeh, B.; Karaman, R. Resistance of gram-negative bacteria to current antibacterial agents and approaches to resolve it. Molecules, 2020, 25(6), 1340.
[http://dx.doi.org/10.3390/molecules25061340] [PMID: 32187986]
[10]
Pendleton, J.N.; Gorman, S.P.; Gilmore, B.F. Clinical relevance of the ESKAPE pathogens. Expert Rev. Anti Infect. Ther., 2013, 11(3), 297-308.
[http://dx.doi.org/10.1586/eri.13.12] [PMID: 23458769]
[11]
Wright, H.T.; Reynolds, K.A. Antibacterial targets in fatty acid biosynthesis. Curr. Opin. Microbiol., 2007, 10(5), 447-453.
[http://dx.doi.org/10.1016/j.mib.2007.07.001] [PMID: 17707686]
[12]
Heath, R.J.; Yu, Y.T.; Shapiro, M.A.; Olson, E.; Rock, C.O. Broad spectrum antimicrobial biocides target the FabI component of fatty acid synthesis. J. Biol. Chem., 1998, 273(46), 30316-30320.
[http://dx.doi.org/10.1074/jbc.273.46.30316] [PMID: 9804793]
[13]
Qiu, X.; Abdel-Meguid, S.S.; Janson, C.A.; Court, R.I.; Smyth, M.G.; Payne, D.J. Molecular basis for triclosan activity involves a flipping loop in the active site. Protein Sci., 1999, 8(11), 2529-2532.
[http://dx.doi.org/10.1110/ps.8.11.2529] [PMID: 10595560]
[14]
Tyers, M.; Wright, G.D. Drug combinations: A strategy to extend the life of antibiotics in the 21st century. Nat. Rev. Microbiol., 2019, 17(3), 141-155.
[http://dx.doi.org/10.1038/s41579-018-0141-x] [PMID: 30683887]
[15]
Mandel, S.; Michaeli, J.; Nur, N.; Erbetti, I.; Zazoun, J.; Ferrari, L.; Felici, A.; Cohen-Kutner, M.; Bachnoff, N. OMN6 a novel bioengineered peptide for the treatment of multidrug resistant gram negative bacteria. Sci. Rep., 2021, 11(1), 6603.
[http://dx.doi.org/10.1038/s41598-021-86155-9] [PMID: 33758343]
[16]
Neha; Dwivedi, A.R.; Kumar, R.; Kumar, V. Recent synthetic strategies for monocyclic azole nucleus and its role in drug discovery and development. Curr. Org. Synth., 2018, 15(3), 321-340.
[http://dx.doi.org/10.2174/1570179414666171013154337]
[17]
Dadashpour, S.; Emami, S. Indole in the target-based design of anticancer agents: A versatile scaffold with diverse mechanisms. Eur. J. Med. Chem., 2018, 150, 9-29.
[http://dx.doi.org/10.1016/j.ejmech.2018.02.065] [PMID: 29505935]
[18]
Dorababu, A. Indole–a promising pharmacophore in recent antiviral drug discovery. RSC Medicinal Chemistry, 2020, 11(12), 1335-1353.
[http://dx.doi.org/10.1039/D0MD00288G] [PMID: 34095843]
[19]
Thanikachalam, P.V.; Maurya, R.K.; Garg, V.; Monga, V.; Monga, V. An insight into the medicinal perspective of synthetic analogs of indole: A review. Eur. J. Med. Chem., 2019, 180, 562-612.
[http://dx.doi.org/10.1016/j.ejmech.2019.07.019] [PMID: 31344615]
[20]
Konus, M.; Çetin, D. Yılmaz, C.; Arslan, S.; Mutlu, D.; Kurt-Kızıldoğan, A.; Otur, Ç.; Ozok, O.; AS Algso, M.; Kivrak, A. Synthesis, biological evaluation and molecular docking of novel thiophene‐based indole derivatives as potential antibacterial, GST inhibitor and apoptotic anticancer agents. ChemistrySelect, 2020, 5(19), 5809-5814.
[http://dx.doi.org/10.1002/slct.202001523]
[21]
Chadha, N.; Silakari, O. Indoles as therapeutics of interest in medicinal chemistry: Bird’s eye view. Eur. J. Med. Chem., 2017, 134, 159-184.
[http://dx.doi.org/10.1016/j.ejmech.2017.04.003] [PMID: 28412530]
[22]
Fung, S.; Xu, C.; Hamel, E.; Wager-Miller, J.B.; Woodruff, G.; Miller, A.; Sanford, C.; Mackie, K.; Stella, N. Novel indole-based compounds that differentiate alkylindole-sensitive receptors from cannabinoid receptors and microtubules: Characterization of their activity on glioma cell migration. Pharmacol. Res., 2017, 115, 233-241.
[http://dx.doi.org/10.1016/j.phrs.2016.10.025] [PMID: 27832960]
[23]
Kikugawa, Y. A Simple Synthesis of N -Acyl- and N -Sulfonylindoles. Synthesis, 1981, 1981(6), 460-461.
[http://dx.doi.org/10.1055/s-1981-29483]
[24]
Shaikh, M.A.; Debebe, H. Synthesis and evaluation of antimicrobial activities of novel N-Substituted indole derivatives. J. Chem., 2020, 2020, 4358453.
[25]
Wiegand, I.; Hilpert, K.; Hancock, R.E.W. Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat. Protoc., 2008, 3(2), 163-175.
[http://dx.doi.org/10.1038/nprot.2007.521] [PMID: 18274517]
[26]
Bonev, B.; Hooper, J.; Parisot, J. Principles of assessing bacterial susceptibility to antibiotics using the agar diffusion method. J. Antimicrob. Chemother., 2008, 61(6), 1295-1301.
[http://dx.doi.org/10.1093/jac/dkn090] [PMID: 18339637]
[27]
Balouiri, M.; Sadiki, M.; Ibnsouda, S.K. Methods for in vitro evaluating antimicrobial activity: A review. J. Pharm. Anal., 2016, 6(2), 71-79.
[http://dx.doi.org/10.1016/j.jpha.2015.11.005] [PMID: 29403965]
[28]
Ioakimidis, L.; Thoukydidis, L.; Mirza, A.; Naeem, S.; Reynisson, J. Benchmarking the reliability of QikProp. Correlation between experimental and predicted values. QSAR Comb. Sci., 2008, 27(4), 445-456.
[http://dx.doi.org/10.1002/qsar.200730051]

Rights & Permissions Print Cite
Article Metrics
38
3
© 2024 Bentham Science Publishers | Privacy Policy